bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitosis-Specific Hyperphosphorylation of Epstein-Barr Virus Nuclear Antigen 2 Suppresses Its Function
Authors: Yue Wei , Davenport Matthew G. , Shackelford Julia , Pagano Joseph S.
Published: March 2004

The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) is a key gene expressed in EBV type III latent infection that can transactivate numerous promoters, including those for all the other type III viral latency genes as well as cellular genes responsible for cell proliferation. EBNA-2 is essential for EBV-mediated immortalization of primary B lymphocytes. We now report that EBNA-2, a phosphoprotein, is hyperphosphorylated specifically in mitosis. Evidence that the cyclin-dependent kinase p34
cdc2
may be involved in this hyperphosphorylation includes (i) coimmunoprecipitation of EBNA-2 and p34
cdc2
, suggesting physical association; (ii) temporal correlation between hyperphosphorylation of EBNA-2 and an increase in p34
cdc2
kinase activity; and (iii) ability of purified p34
cdc2
/cyclin B1 kinase to phosphorylate EBNA-2 in vitro. Hyperphosphorylation of EBNA-2 appears to suppress its ability to transactivate the latent membrane protein 1 (LMP-1) promoter by about 50%. The association between EBNA-2 and PU.1 is also decreased by about 50% in M-phase-arrested cells, as shown by coimmunoprecipitation from cell lysates, suggesting that hyperphosphorylation of EBNA-2 impairs its affinity for PU.1. Finally, endogenous LMP-1 mRNA levels in M phase are around 55% of those in asynchronously growing cells. These results suggest that regulation of gene expression during type III latency may be regulated in a cell-cycle-related manner.
The Vaccinia Virus K1L Gene Product Inhibits Host NF-κB Activation by Preventing IκBα Degradation
Authors: Shisler Joanna L. , Jin Xiao-Lu
Published: March 2004

Vaccinia virus wild-type strains such as Ankara and WR synthesize proteins capable of inhibiting the activation of host NF-κB, a family of transcription factors that regulate the expression of inflammatory genes. In contrast, an infection by the attenuated MVA strain, whose genome lacks many immunoregulatory genes present in the DNA of its Ankara parent, induces NF-κB activation. Insertion of NF-κB inhibitory genes into the MVA DNA, then, would alter the MVA phenotype. By this method, a 5.2-kb region of Ankara DNA containing the K1L gene and two other genes that are absent in the MVA genome that was identified as NF-κB was inhibited in cells infected with the MVA/5.2kb virus. To determine if K1L was responsible, the relevant biological properties of both a recombinant MVA containing a copy of the WR strain's K1L (MVA/K1L) and a WR deletion mutant lacking the K1L gene (ΔK1L) were examined. Indeed, unlike its progenitor, the altered MVA halted degradation of the host regulatory protein IκBα—a key event in the pathway of transcriptional activation by NF-κB factors. Moreover, MVA/K1L gained the ability to repress artificially contrived and natural NF-κB-regulated expression of a transfected luciferase and the cellular tumor necrosis factor gene, respectively. In contrast, although these functions could also be performed by WR, the ΔK1L virus lost these abilities. Thus, one apparent molecular function of K1L is to prevent IκBα degradation. This impediment to NF-κB-induced host proinflammatory gene expression, in turn, might enhance virus survival.
Differential Tissue-Specific Regulation of Antiviral CD8+T-Cell Immune Responses during Chronic Viral Infection
Authors: Zhou Shenghua , Ou Rong , Huang Lei , Price Graeme E. , Moskophidis Demetrius
Published: March 2004

The hallmarks of the immune response to viral infections are the expansion of antigen-specific CD8+cytotoxic T lymphocytes (CTLs) after they encounter antigen-presenting cells in the lymphoid tissues and their subsequent redistribution to nonlymphoid tissues to deal with the pathogen. Control mechanisms exist within CTL activation pathways to prevent inappropriate CTL responses against disseminating infections with a broad distribution of pathogen in host tissues. This is demonstrated during overwhelming infection with the noncytolytic murine lymphocytic choriomeningitis virus, in which clonal exhaustion (anergy and/or deletion) of CTLs prevents immune-mediated pathology but allows persistence of the virus. The mechanism by which the immune system determines whether or not to mount a full response to such infections is unknown. Here we present data showing that the initial encounter of specific CTLs with infected cells in lymphoid tissues is critical for this decision. Whether the course of the viral infection is acute or persistent for life primarily depends on the degree and kinetics of CTL exhaustion in infected lymphoid tissues. Virus-driven CTL expansion in lymphoid tissues resulted in the migration of large quantities of CTLs to nonlymphoid tissues, where they persisted at stable levels. Surprisingly, although virus-specific CTLs were rapidly clonally exhausted in lymphoid tissues under conditions of chronic infection, a substantial number of them migrated to nonlymphoid tissues, where they retained an effector phenotype for a long time. However, these cells were unable to control the infection and progressively lost their antiviral capacities (cytotoxicity and cytokine secretion) in a hierarchical manner before their eventual physical elimination. These results illustrate the differential tissue-specific regulation of antiviral T-cell responses during chronic infections and may help us to understand the dynamic relationship between antigen and T-cell populations in many persistent infections in humans.
Transgenic Mice Expressing the Nucleoprotein of Borna Disease Virus in either Neurons or Astrocytes: Decreased Susceptibility to Homotypic Infection and Disease
Authors: Rauer Mathias , Götz Jürgen , Schuppli Daniel , Staeheli Peter , Hausmann Jürgen
Published: March 2004

The nucleoprotein (N) of Borna disease virus (BDV) is the major target of the disease-inducing antiviral CD8 T-cell response in the central nervous system of mice. We established two transgenic mouse lines which express BDV-N in either neurons (Neuro-N) or astrocytes (Astro-N). Despite strong transgene expression, neurological disease or gross behavioral abnormalities were not observed in these animals. When Neuro-N mice were infected as adults, replication of BDV was severely impaired and was restricted to brain areas with a low density of transgene-expressing cells. Notably, the virus failed to replicate in the transgene-expressing granular and pyramidal neurons of the hippocampus (which are usually the preferred host cells of BDV). When Neuro-N mice were infected within the first 5 days of life, replication of BDV was not suppressed in most neurons, presumably because the onset of transgene expression in the brain occurred after these cells became infected with BDV. Astro-N mice remained susceptible to BDV infection, but they were resistant to BDV-induced neurological disorder. Unlike their nontransgenic littermates, Neuro-N mice with persistent BDV infection did not develop neurological disease after immunization with a vaccinia virus vector expressing BDV-N. In contrast to the situation in wild-type mice, this treatment also failed to induce N-specific CD8 T cells in the spleens of both transgenic mouse lines. Thus, while resistance to BDV infection in N-expressing neurons appeared to result from untimely expression of a viral nucleocapsid component, the resistance to BDV-induced neuropathology probably resulted from immunological tolerance.
Comparative Molecular Analysis of the Abnormal Prion Protein in Field Scrapie Cases and Experimental Bovine Spongiform Encephalopathy in Sheep by Use of Western Blotting and Immunohistochemical Methods
Authors: Lezmi Stéphane , Martin Stuart , Simon Stéphanie , Comoy Emmanuel , Bencsik Anna , Deslys Jean-Philippe , Grassi Jacques , Jeffrey Martin , Baron Thierry
Published: March 2004

Since the appearance of bovine spongiform encephalopathy (BSE) in cattle and its linkage with the human variant of Creutzfeldt-Jakob disease, the possible spread of this agent to sheep flocks has been of concern as a potential new source of contamination. Molecular analysis of the protease cleavage of the abnormal prion protein (PrP), by Western blotting (PrP
res
) or by immunohistochemical methods (PrP
d
), has shown some potential to distinguish BSE and scrapie in sheep. Using a newly developed enzyme-linked immunosorbent assay, we identified 18 infected sheep in which PrP
res
showed an increased sensitivity to proteinase K digestion. When analyzed by Western blotting, two of them showed a low molecular mass of unglycosylated PrP
res
as found in BSE-infected sheep, in contrast to other naturally infected sheep. A decrease of the labeling by P4 monoclonal antibody, which recognizes an epitope close to the protease cleavage site, was also found by Western blotting in the former two samples, but this was less marked than in BSE-infected sheep. These two samples, and all of the other natural scrapie cases studied, were clearly distinguishable from those from sheep inoculated with the BSE agent from either French or British cattle by immunohistochemical analysis of PrP
d
labeling in the brain and lymphoid tissues. Final characterization of the strain involved in these samples will require analysis of the features of the disease following infection of mice, but our data already emphasize the need to use the different available methods to define the molecular properties of abnormal PrP and its possible similarities with the BSE agent.
Movement Protein of a Closterovirus Is a Type III Integral Transmembrane Protein Localized to the EndoplasmicReticulum
Authors: Peremyslov Valera V. , Pan Yung-Wei , Dolja Valerian V.
Published: March 2004

Cell-to-cell movement of beet yellows closterovirus requires four structural proteins and a 6-kDa protein (p6) that is a conventional, nonstructural movement protein. Here we demonstrate that either virus infection or p6 overexpression results in association of p6 with the rough endoplasmic reticulum. The p6 protein possesses a single-span, transmembrane, N-terminal domain and a hydrophilic, C-terminal domain that is localized on the cytoplasmic face of the endoplasmic reticulum. In the infected cells, p6 forms a disulfide bridge via a cysteine residue located near the protein's N terminus. Mutagenic analyses indicated that each of the p6 domains, as well as protein dimerization, is essential for p6 function in virus movement.
The Subcellular Distribution of Multigene Family 110 Proteins of African Swine Fever Virus Is Determined by Differences in C-Terminal KDEL Endoplasmic Reticulum Retention Motifs
Authors: Netherton Christopher , Rouiller Isabelle , Wileman Thomas
Published: March 2004

African swine fever virus (ASFV) is a large double-stranded DNA virus that replicates in discrete areas in the cytosol of infected cells called viral factories. Recent studies have shown that assembling virions acquire their internal envelopes through enwrapment by membranes derived from the endoplasmic reticulum (ER). However, the mechanisms that underlie the formation of viral factories and progenitor viral membranes are as yet unclear. Analysis of the published genome of the virus revealed a conserved multigene family that encodes proteins with hydrophobic signal sequences, indicating possible translocation into the ER lumen. Strikingly, two of these genes,
XP124L
and
Y118L
, encoded proteins with KDEL-like ER retention motifs. Analysis of
XP124L
and
Y118L
gene product by biochemical and immunofluorescence techniques showed that the proteins were localized to pre-Golgi compartments and that the KEDL motif at the C terminus of pXP124L was functional.
XP124L
expression, in the absence of other ASFV genes, had a dramatic effect on the contents of the ER that was dependent precisely on the C-terminal sequence KEDL. The normal subcellular distribution of a number of proteins resident to this important, cellular organelle was drastically altered in cells expressing wild-type
XP124L
gene product. PXP124L formed unusual perinuclear structures that contained resident ER proteins, as well as proteins of the ER-Golgi intermediate compartment. The data presented here hint at a role for MGF110 gene product in preparing the ER for its role in viral morphogenesis; this and other potential functions are discussed.
Positive Selection Detection in 40,000 HumanImmunodeficiency Virus (HIV) Type 1 Sequences Automatically IdentifiesDrug Resistance and Positive Fitness Mutations in HIV Proteaseand ReverseTranscriptase
Authors: Chen Lamei , Perlina Alla , Lee Christopher J.
Published: March 2004

Drug
resistance is a major problem in the treatment of AIDS, due to the very
high mutation rate of human immunodeficiency virus (HIV) and subsequent
rapid development of resistance to new drugs. Identification of
mutations associated with drug resistance is critical for both
individualized treatment selection and new drug design. We have
performed an automated mutation analysis of HIV Type 1 (HIV-1) protease
and reverse transcriptase (RT) from approximately 40,000 AIDS patient
plasma samples sequenced by Specialty Laboratories Inc. from 1999 to
mid-2002. This data set provides a nearly complete mutagenesis of HIV
protease and enables the calculation of statistically significant

K
a

/

K
s

values for each
individual amino acid mutation in protease and RT. Positive selection
(i.e., a

K
a

/

K
s

ratio of>
1, indicating increased reproductive fitness) detected 19 of
23 known drug-resistant mutation positions in protease and 20 of 34
such positions in RT. We also discovered 163 new amino acid mutations
in HIV protease and RT that are strong candidates for drug resistance
or fitness. Our results match available independent data on protease
mutations associated with specific drug treatments and mutations with
positive reproductive fitness, with high statistical significance (the
P
values for the observed matches to occur by random chance
are 10
−5.2
and 10
−16.6
,
respectively). Our mutation analysis provides a valuable resource for
AIDS research and will be available to academic researchers upon
publication at
http://www.bioinformatics.ucla.edu/HIV
.
Our data indicate that positive selection mapping is an analysis that
can yield powerful insights from high-throughput sequencing of rapidly
mutating
pathogens.
Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion
Authors: Zaitsev Viatcheslav , von Itzstein Mark , Groves Darrin , Kiefel Milton , Takimoto Toru , Portner Allen , Taylor Garry
Published: March 2004

Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.
Low pH Is Required for Avian Sarcoma and Leukosis Virus Env-Induced Hemifusion and Fusion Pore Formation but Not for Pore Growth
Authors: Melikyan G. B. , Barnard R. J. O. , Markosyan R. M. , Young J. A. T. , Cohen F. S.
Published: March 2004

Binding of avian sarcoma and leukosis virus (ASLV) to its cognate receptor on the cell surface causes conformational changes in its envelope protein (Env). It is currently debated whether low pH is required for ASLV infection. To elucidate the role of low pH, we studied the association between ASLV subgroup B (ASLV-B) and liposomes and fusion between effector cells expressing Env from ASLV-A and ASLV-B and target cells expressing cognate receptors. Neither EnvA nor EnvB promoted cell-cell fusion at neutral pH, but lowering the pH resulted in quick and extensive fusion. As expected for a low-pH-triggered reaction, fusion was a steep function of pH. Steps that required low pH were identified. Binding a soluble form of the receptor caused ASLV-B to hydrophobically associate with liposome membranes at neutral pH, indicating that low pH is not required for insertion of Env's fusion peptides into membranes. But both cell-cell hemifusion and fusion pore formation were pH dependent. It is proposed that fusion peptide insertion stabilizes the conformation of ASLV Env into a form that can be acted upon by low pH. At this point, but not before, low pH can induce fusion and is in fact required for fusion to occur. However, low pH is no longer necessary after formation of the initial fusion pore: pore enlargement does not require low pH.
Acupuncture for chronic headache in primary care: large, pragmatic, randomised trial
Authors: Vickers Andrew J , Rees Rebecca W , Zollman Catherine E , McCarney Rob , Smith Claire M , Ellis Nadia , Fisher Peter , Van Haselen Robbert
Published: March 2004

Objective To determine the effects of a policy of “use acupuncture” on headache, health status, days off sick, and use of resources in patients with chronic headache compared with a policy of “avoid acupuncture.”

Design Randomised, controlled trial.

Setting General practices in England and Wales.

Participants 401 patients with chronic headache, predominantly migraine.

Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months or to a control intervention offering usual care.

Main outcome measures Headache score, SF-36 health status, and use of medication were assessed at baseline, three, and 12 months. Use of resources was assessed every three months.

Results Headache score at 12 months, the primary end point, was lower in the acupuncture group (16.2, SD 13.7, n = 161, 34%
reduction from baseline) than in controls (22.3, SD 17.0, n = 140, 16% reduction from baseline). The adjusted difference between means is 4.6 (95% confidence interval 2.2 to 7.0; P = 0.0002). This result is robust to sensitivity analysis incorporating imputation for missing data. Patients in the acupuncture group experienced the equivalent of 22 fewer days of headache per year (8 to 38). SF-36 data favoured acupuncture, although differences reached significance only for physical role functioning, energy, and change in health. Compared with controls, patients randomised to acupuncture used 15% less medication (P = 0.02), made 25% fewer visits to general practitioners (P = 0.10), and took 15% fewer days off sick (P = 0.2).

Conclusions Acupuncture leads to persisting, clinically relevant benefits for primary care patients with chronic headache, particularly migraine. Expansion of NHS acupuncture services should be considered.
Does it matter what a hospital is “high volume” for? Specificity of hospital volume-outcome associations for surgical procedures: analysis of administrative data
Authors: Urbach David R , Baxter Nancy N
Published: March 2004

Objective To determine whether the improved outcome of a surgical procedure in high volume hospitals is specific to the volume of the same procedure.

Design and setting Analysis of secondary data in Ontario, Canada.

Participants Patients having an oesophagectomy, colorectal resection for cancer, pancreaticoduodenectomy, major lung resection for cancer, or repair of an unruptured abdominal aortic aneurysm between 1994 and 1999.

Main outcome measures Odds ratio for death within 30 days of surgery in relation to the hospital volume of the same surgical procedure and the hospital volume of the other four procedures. Estimates were adjusted for age, sex, and comorbidity and accounted for hospital level clustering.

Results With the exception of colorectal resection, 30 day mortality seemed to be inversely related not only to the hospital volume of the same procedure but also to the hospital volume of most of the other procedures. In some cases the effect of the volume of a different procedure was stronger than the effect of the volume of the same procedure. For example, the association of mortality from pancreaticoduodenectomy with hospital volume of lung resection (odds ratio for death in hospitals with a high volume of lung resection compared with low volume 0.36, 95% confidence interval 0.23 to 0.57) was much stronger than the association of mortality from pancreaticoduodenectomy with hospital volume of pancreaticoduodenectomy (0.76, 0.44 to 1.32).

Conclusion The inverse association between high volume of procedure and risk of operative death is not specific to the volume of the procedure being studied.
National cross sectional survey to determine whether the decision to delivery interval is critical in emergency caesarean section
Authors: Thomas Jane , Paranjothy Shantini , James David
Published: March 2004

Objective To examine the association between decision to delivery interval and maternal and baby outcomes.

Design National cross sectional survey.

Setting Maternity units in England and Wales.

Subjects reviewed 17 780 singleton births (99% of all births) delivered by emergency caesarean section in England and Wales between 1 May 2000 and 31 July 2000.

Main outcome measures Association between decision to delivery interval and baby outcomes (Apgar scores of < 7 and < 4 at five minutes and stillbirth) and maternal outcomes (requirement for special care additional to routine care after caesarean section and where care was provided).

Results Compared with babies delivered within 15 minutes, there was no difference in maternal or baby outcome for decision to delivery interval between 16 and 75 minutes. After 75 minutes, however, there was a significantly higher odds of a five minute Apgar score of < 7 (odds ratio 1.7, 95% confidence interval 1.2 to 2.4), and 50% increase in odds of special care additional to routine care for mothers.

Conclusion A decision to delivery interval of 30 minutes is not an absolute threshold for influencing baby outcome. Decision to delivery intervals of more than 75 minutes are associated with poorer maternal and baby outcomes and should be avoided.
Cost effectiveness analysis of a randomised trial of acupuncture for chronic headache in primary care
Authors: Wonderling David , Vickers Andrew J , Grieve Richard , McCarney Rob
Published: March 2004

Objective To evaluate the cost effectiveness of acupuncture in the management of chronic headache.

Design Cost effectiveness analysis of a randomised controlled trial.

Setting General practices in England and Wales.

Participants 401 patients with chronic headache, predominantly migraine.

Interventions Patients were randomly allocated to receive up to 12 acupuncture treatments over three months from appropriately trained physiotherapists, or to usual care alone.

Main outcome measure Incremental cost per quality adjusted life year (QALY) gained.

Results Total costs during the one year period of the study were on average higher for the acupuncture group (£403; $768;€598) than for controls (£217) because of the acupuncture practitioners' costs. The mean health gain from acupuncture during the one year of the trial was 0.021 quality adjusted life years (QALYs), leading to a base case estimate of £9180 per QALY gained. This result was robust to sensitivity analysis. Cost per QALY dropped substantially when the analysis incorporated likely QALY differences for the years after the trial.

Conclusions Acupuncture for chronic headache improves health related quality of life at a small additional cost; it is relatively cost effective compared with a number of other interventions provided by the NHS.
Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT)
Authors: Gertsch Jeffrey H , Basnyat Buddha , Johnson E William , Onopa Janet , Holck Peter S
Published: March 2004

Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness.

Design Prospective, double blind, randomised, placebo controlled trial.

Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002.

Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent.

Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache.

Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70).

Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.
An outbreak of gastroenteritis from a non-chlorinated community water supply
Authors: Kuusi M , Klemets P , Miettinen I , Laaksonen I , Sarkkinen H , Hänninen M L , Rautelin H , Kela E , Nuorti J P
Published: March 2004

Study objective:To determine the source and the extent of a community wide outbreak of gastroenteritis.

Design:A matched case-control study with postal questionnaires. Subtyping of campylobacter strains by pulsed field gel electrophoresis (PFGE).

Setting:A rural municipality with a population of 8600 in southern Finland, August 2000. Two thirds of the population receive non-chlorinated ground water from the municipal water supply.

Participants:Cases were randomly selected among residents of the municipality who contacted the municipal health centre because of gastroenteritis and had illness onset between 31 July and 20 August 2000. Community controls were identified from the population registry and matched according to sex, year of birth, and postal code.

Main results:Four hundred and sixty three persons contacted the municipal health centre because of gastroenteritis.Campylobacter jejuniwas isolated from stool samples of 24 persons. One hundred and thirty seven cases and 388 controls were enrolled in the case-control study. In multivariate analysis, drinking unboiled water from the municipal supply was significantly associated with illness (odds ratio 11.1, 95% confidence interval 1.4 to 90.2).C jejuniwas isolated from one tap water sample. The water isolate and all but one of the patient isolates were indistinguishable by PFGE.

Conclusions:Combining epidemiological investigation with molecular subtyping methods provided strong evidence that water was the source of the outbreak. Non-chlorinated small ground water systems may be susceptible to waterborne outbreaks and constitute a risk to rural populations.
Social capital and collective efficacy in Hungary: cross sectional associations with middle aged female and male mortality rates
Authors: Skrabski Á , Kopp M , Kawachi I
Published: March 2004

Objectives:Social capital, collective efficacy, and religious involvement have each been linked to population health. This study examined the relations between these measures and male/female mortality rates in Hungary.

Design:Cross sectional, ecological study.

Setting:150 sub-regions of Hungary.

Participants and methods:12 643 people were interviewed in 2002 (the “Hungarostudy 2002” survey). Social capital was measured by lack of social trust, reciprocity between citizens, and membership in civil organisations. Collective efficacy was measured by survey items from the Project on Human Development in Chicago Neighborhoods. Religious involvement was measured by church attendance.

Main outcome measure:Gender specific all cause mortality rates for the middle aged population (45–64 years) in the 150 sub-regions of Hungary, provided by the Central Statistical Office (CSO).

Results:Social capital, collective efficacy, as well as religious involvement were each significantly associated with middle age mortality. After education, collective efficacy showed the strongest association with mortality in both men and women. Among men, socioeconomic status, collective efficacy, social distrust, competitive attitude, reciprocity, and membership of civic organisations explained 68.0% of the sub-regional variations in mortality rates. Among women the same variables explained only 29.3% of the variance in mortality rates. Religious involvement was protective among women.

Conclusion:Collective efficacy and social capital are significant predictors of mortality rates in both men and women across sub-regions of Hungary. Gender differences in the relative importance of social factors may help to explain the differential impact of economic transformation on mortality rates for men and women in Central-Eastern European countries.
Providing treatment for hepatitis C in an Australian district centre
Authors: Ewart A , Harrison L , Joyner B , Safe A
Published: March 2004

Hepatitis C virus (HCV) poses a major public health problem world wide. The introduction of combined therapy (interferon and ribavirin) and the recent development of pegylated interferon have offered the opportunity to alter the natural history of HCV, potentially reducing morbidity and mortality. Until recently, treatment has been confined to larger Australian cities. This paper describes the establishment of a clinic for the treatment of HCV in a regional Australian city. The facilities of the sexual health clinic were utilised. Factors contributing to the success of the clinic include the specialist nurse, a multidisciplinary approach, and the service model of shared care with general practitioners. The patient population and the outcomes of managing HCV in a regional centre are described. The sustained viral response rate is comparable to the published data from specialist centres.
Breast cancer recurrence: follow up after treatment for primary breast cancer
Authors: Hiramanek N
Published: March 2004

Background

Breast cancer will affect one in 12 Australian women in their lifetime. After potentially curative treatment, it is usual for patients to be followed up for many years. However, controversies surround follow up, and its value is uncertain.

Aim

This study reviews the evidence and describes the role of routine follow up in the management of breast cancer in a tertiary hospital. By establishing how recurrence of breast cancer presents and identifying the proportion of patients with recurrence who were diagnosed as a consequence of regular follow up, the value of this system in detecting recurrence can be indirectly assessed.

Design

A retrospective review was undertaken of all patients attending the radiotherapy outpatient clinic for treatment of invasive breast cancer in 1997. Hospital records were reviewed to ascertain patient and tumour characteristics, treatment received, site of recurrence and its mode of detection, whether patients were symptomatic at the time of recurrence, and whether they presented at a scheduled appointment.

Results

Out of 286 patients who presented to the radiotherapy outpatient clinic, 220 were entered into the study. Recurrence was recorded in 42 patients (a complete dataset was available for 38 of these patients). In total, 74% (31/42) of recurrences were symptomatic, and 76% (32/42) presented at unscheduled appointments, the majority (17/32) of which were initiated by the patient. Only seven patients had asymptomatic recurrences.

Conclusion

Based on current evidence, long term routine hospital follow up after treatment for breast cancer appears to be inefficient in detecting recurrence.
How to assess epidemiological studies
Authors: Zaccai J H
Published: March 2004

Assessing the quality of an epidemiological study equates to assessing whether the inferences drawn from it are warranted when account is taken of the methods, the representativeness of the study sample, and the nature of the population from which it is drawn. Bias, confounding, and chance can threaten the quality of an epidemiological study at all its phases. Nevertheless, their presence does not necessarily imply that a study should be disregarded. The reader must first balance any of these threats or missing information with their potential impact on the conclusions of the report.
Implementation of British Thoracic Society guidelines for acute exacerbation of chronic obstructive pulmonary disease: impact on quality of life
Authors: Dheda K , Crawford A , Hagan G , Roberts C M
Published: March 2004

Background

The British Thoracic Society (BTS) guidelines have not been examined collectively for their impact on chronic obstructive pulmonary disease (COPD). Whether intensive outpatient follow up of COPD patients after acute admission, using these guidelines, improved quality of life compared to the “usual practice” of primary care follow up was investigated.

Methods

Altogether 103 patients with a new diagnosis of COPD were admitted and screened over a four year period. Seventy patients were excluded because of another dominant medical condition or a mandatory requirement for intervention. Patients were randomised to regular primary care (control group, n = 15) or chest clinic follow up (intervention group, n = 10). Spirometry, oxygen saturation, St George’s Respiratory Questionnaire (SGRQ), and Short Form 36 questionnaire were measured at baseline and six months. The intervention group was reviewed at least four times in the six month period and received spirometry, ambulatory oxygen assessment, smoking cessation advice, nebuliser assessment, a steroid trial, advice about nutrition/exercise, and introduction to a patient support group.

Results

There was no significant difference between baseline measurements in the two groups. There was a significant mean (SD) improvement in the SGRQ symptom score from baseline to six months in the intervention group [20.98 (20.36)] compared with the controls [0.23 (12.55)] (p = 0.004). At six months the SGRQ symptom score, impact score, and total score was significantly better in the intervention than the control group (p = 0.01, 0.02, and 0.02).

Conclusion

Aggressive implementation of BTS guidelines after initial hospitalisation may improve respiratory health specific quality of life scores in patients with COPD. Larger studies are needed to confirm this finding.
How to avoid being sued in clinical practice
Authors: Panting G
Published: March 2004

Challenges to clinical management are a fact of professional life. Every doctor must expect to become embroiled in complaints and claims from time to time and be prepared to justify why they managed a particular case in the way that they did. Good medical practice is defensible practice, which depends upon staying within the limits of your own expertise, keeping up to date and conducting audit, ensuring your administration is effective and that patients are not allowed to slip through the net, that you communicate effectively with patients, their carers and colleagues, and that medical records recall all salient facts relating to the patient.

If things go wrong, be open, investigate the facts, explain the situation fully to the patient, and do not be afraid to apologise.
DISTRIBUTED SENSOR NETWORKS: A CELLULAR NONLINEAR NETWORK PERSPECTIVE
Authors: HAENGGI MARTIN
Published: March 2004

Large-scale networks of integrated wireless sensors become increasingly tractable. Advances in hardware technology and engineering design have led to dramatic reductions in size, power consumption, and cost for digital circuitry, and wireless communications. Networking, self-organization, and distributed operation are crucial ingredients to harness the sensing, computing, and computational capabilities of the nodes into a complete system. This article shows that those networks can be considered as cellular nonlinear networks (CNNs), and that their analysis and design may greatly benefit from the rich theoretical results available for CNNs.
CMOS REALIZATION OF A 2-LAYER CNN UNIVERSAL MACHINE CHIP
Authors: CARMONA R. , JIMÉNEZ-GARRIDO F. , DOMÍNGUEZ-CASTRO R. , ESPEJO S. , RODRÍGUEZ-VÁZQUEZ A.
Published: March 2004

Some features of the biological retina can be modelled by a 2-layer cellular neural network (CNN) composed of locally connected elementary nonlinear processors. In order to explore these complex spatiotemporal dynamics for image processing, a prototype chip has been designed and fabricated in a 0.5μm CMOS technology. Design challenges, trade-offs, the building blocks and the tests results for this system with 0.5×106 transistors, most of them operating in analog mode, are presented in this paper.
THE ROLE OF FIELD COUPLING IN NANO-SCALE CELLULAR NONLINEAR NETWORKS
Authors: POROD WOLFGANG , CSABA GYÖRGY , CSURGAY ÁRPÁD
Published: March 2004

We review some of our previous work on field-coupling in nano-scale cellular arrays. Electronic devices based on metallic and magnetic nanoscale dots and molecular structures have been suggested, however, no technologically viable architecture for nanoelectronic circuit integration has emerged so far. A natural architecture on the nanoscale appears to be near-neighbor cellular networking, and we explore promising alternative ways of integrating nanodevices by direct physical field coupling, i.e. either by Coulomb or by magnetic interactions. We review new architectures for such field-coupled nanocircuits.
REALIZATION OF COUPLINGS IN A POLYNOMIAL TYPE MIXED-MODE CELLULAR NEURAL NETWORK
Authors: LAIHO MIKA , PAASIO ARI , KANANEN ASKO , HALONEN KARI
Published: March 2004

In this paper realization of couplings between cells in a polynomial type mixed-mode cellular neural network (CNN) is analyzed. The choice of the multiplier is discussed and two multiplier types are analyzed. Also, two circuits for generating the second and third order polynomial terms of cell output are described. The accuracy of the multipliers and polynomial circuits at the presence of device mismatch is analyzed.
SC-CNNs for Chaotic Signal Applications in Secure Communication Systems
Authors: Caponetto Riccardo , Fortuna Luigi , Occhipinti Luigi , Xibilia Maria Gabriella
Published: March 2004

In this paper a CNNs based circuit for the generation of hyperchaotic signals is proposed. The circuit has been developed for applications in secure communication systems. An Saito oscillator has been designed by using a suitable configuration of a four-cells State-Controlled CNNs. A cryptography system based on the Saito oscillator has been implemented by using inverse system synchronization. The proposed circuit implementation and experimental results are given.
ANALYSIS OF MULTIDIMENSIONAL NEURAL ACTIVITY VIA CNN-UM
Authors: GÁL VIKTOR , GRÜN SONJA , TETZLAFF RONALD
Published: March 2004

In this paper we show that the Cellular Nonlinear Network Universal Machine (CNN-UM) is an excellent tool for analyzing time series of multidimensional binary signals. The developed algorithm is dedicated to process electrophysiological multi-neuron recordings: our aim is to find specific multidimensional activity patterns, which may reflect higher order functional cell-assemblies. The analysis consists of two parts: first, the occurrences of different patterns are counted, then the statistical significance of each occurrence frequency is calculated separately.
CELLULAR NEURAL NETWORKS (CNN) WITH LINEAR WEIGHT FUNCTIONS FOR A PREDICTION OF EPILEPTIC SEIZURES
Authors: TETZLAFF R. , KUNZ R. , NIEDERHÖFER C.
Published: March 2004

In this paper, we present a novel approach to the prediction of epileptic seizures using boolean CNN with linear weight functions. Three different binary pattern occurrence behaviours will be discussed and analysed for several invasive recordings of brain electrical activity. Furthermore analogic binary pattern detection algorithms will be introduced for a possible prediction of epileptic seizures.
SOLVING TRAFFIC JAMS: HUMAN INTERVENTION OR SELF-ORGANIZATION?
Authors: OR ETAY MAR , SHIR ERAN , SOLOMON SORIN
Published: March 2004

We study the effect of external intervention on the self-organized jamming phase transition. The classical traffic model of Biham, Middleton, and Levine (BML) is modified to give priority to longer queues. It is shown that this lowers the critical density at which the jamming transition takes place (in comparison to the original model).
REDUCING THE COMPRESSIBILITY OF A LATTICE BOLTZMANN FLUID USING A REPULSIVE FORCE
Authors: MARCONI STEFAN , CHOPARD BASTIEN , LATT JONAS
Published: March 2004

This paper investigates the possibility to reduce the compressibility of lattice Boltzmann fluid models by introducing a repulsive force between nearest neighbor lattice Boltzmann particles. This new interaction is based on the Shan–Chen model. The interest of this approach is that it implements the physical mechanism responsible for the incompressibility of real fluids and retains the natural interpretation of the fluid density and fluid momentum. The new state equation shows that the compressibility factor decreases as the repulsive interaction increases. However, numerical instabilities limit the value of the acceptable repulsion. We investigate several situations, such as the Poiseuille flow with pressure gradient, a static fluid subject to gravity and the Womersley flow to evaluate the benefits of our approach. Globally, the compressibility of lattice Boltzmann fluids can be reduced by a factor of 4.
DIRECT SIMULATIONS OF SMALL MULTI-FERMION SYSTEMS
Authors: CREUTZ MICHAEL
Published: March 2004

I explore computer simulations of the dynamics of small multi-fermion lattice systems. The method is more general, but I concentrate on Hubbard type models where the fermions hop between a small number of connected sites. I use the natural mapping of fermion occupation numbers onto computer bits. Signs from fermion interchange are reduced to bit counting. The technique inherently requires computer resources growing exponentially with the system volume; so, it restricted to modestly small systems. Large volume results would require combining these techniques with further approximations, perhaps in a recursive renormalization group manner.
MODELING AND COMPUTER SIMULATION OF AN INSURANCE POLICY: A SEARCH FOR MAXIMUM PROFIT
Authors: ACHARYYA MUKTISH , ACHARYYA AJANTA BHOWAL
Published: March 2004

We have developed a model for a life-insurance policy. In this model, the net gain is calculated by computer simulation for a particular type of lifetime distribution function. We observed that the net gain becomes maximum for a particular value of upper age for last premium.
THE USE OF FRACTALS FOR THE STUDY OF THE PSYCHOLOGY OF PERCEPTION: PSYCHOPHYSICS AND PERSONALITY FACTORS, A BRIEF REPORT
Authors: MITINA OLGA V. , ABRAHAM FREDERICK DAVID
Published: March 2004

The present article deals with perception of time (subjective assessment of temporal intervals), complexity and aesthetic attractiveness of visual objects. The experimental research for construction of functional relations between objective parameters of fractals' complexity (fractal dimension and Lyapunov exponent) and subjective perception of their complexity was conducted. As stimulus material we used the program based on Sprott's algorithms for the generation of fractals and the calculation of their mathematical characteristics. For the research 20 fractals were selected which had different fractal dimensions that varied from 0.52 to 2.36, and the Lyapunov exponent from 0.01 to 0.22. We conducted two experiments: (1) A total of 20 fractals were shown to 93 participants. The fractals were displayed on the screen of a computer for randomly chosen time intervals ranging from 5 to 20 s. For each fractal displayed, the participant responded with a rating of the complexity and attractiveness of the fractal using ten-point scale with an estimate of the duration of the presentation of the stimulus. Each participant also answered the questions of some personality tests (Cattell and others). The main purpose of this experiment was the analysis of the correlation between personal characteristics and subjective perception of complexity, attractiveness, and duration of fractal's presentation. (2) The same 20 fractals were shown to 47 participants as they were forming on the screen of the computer for a fixed interval. Participants also estimated subjective complexity and attractiveness of fractals. The hypothesis on the applicability of the Weber–Fechner law for the perception of time, complexity and subjective attractiveness was confirmed for measures of dynamical properties of fractal images.
A TWELFTH-ORDER FOUR-STEP FORMULA FOR THE NUMERICAL INTEGRATION OF THE ONE-DIMENSIONAL SCHRÖDINGER EQUATION
Authors: WANG ZHONGCHENG , DAI YONGMING
Published: March 2004

A new twelfth-order four-step formula containing fourth derivatives for the numerical integration of the one-dimensional Schrödinger equation has been developed. It was found that by adding multi-derivative terms, the stability of a linear multi-step method can be improved and the interval of periodicity of this new method is larger than that of the Numerov's method. The numerical test shows that the new method is superior to the previous lower orders in both accuracy and efficiency and it is specially applied to the problem when an increasing accuracy is requested.
AUXILIARY EQUATION METHOD AND ITS APPLICATIONS TO NONLINEAR EVOLUTION EQUATIONS
Authors: SIRENDAOREJI  , JIONG SUN
Published: March 2004

By using the solutions of an auxiliary ordinary differential equation, a direct algebraic method is described to construct several exact travelling wave solutions for some nonlinear partial differential equations. By this method some physically important nonlinear equations are investigated and new exact travelling wave solutions are explicitly obtained with the aid of symbolic computation.
NONPARAMETRIC ANALYSES OF LOG-PERIODIC PRECURSORS TO FINANCIAL CRASHES
Authors: ZHOU WEI-XING , SORNETTE DIDIER
Published: March 2004

We apply two nonparametric methods to further test the hypothesis that log-periodicity characterizes the detrended price trajectory of large financial indices prior to financial crashes or strong corrections. The term "parametric" refers here to the use of the log-periodic power law formula to fit the data; in contrast, "nonparametric" refers to the use of general tools such as Fourier transform, and in the present case the Hilbert transform and the so-called (H, q)-analysis. The analysis using the (H, q)-derivative is applied to seven time series ending with the October 1987 crash, the October 1997 correction and the April 2000 crash of the Dow Jones Industrial Average (DJIA), the Standard & Poor 500 and Nasdaq indices. The Hilbert transform is applied to two detrended price time series in terms of the ln (tc-t) variable, where tcis the time of the crash. Taking all results together, we find strong evidence for a universal fundamental log-frequency f=1.02±0.05 corresponding to the scaling ratio λ=2.67±0.12. These values are in very good agreement with those obtained in earlier works with different parametric techniques. This note is extracted from a long unpublished report with 58 figures available at , which extensively describes the evidence we have accumulated on these seven time series, in particular by presenting all relevant details so that the reader can judge for himself or herself the validity and robustness of the results.