bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovering functional gene expression patterns in the metabolic network of Escherichia coli with wavelets transforms
Authors: König Rainer , Schramm Gunnar , Oswald Marcus , Seitz Hanna , Sager Sebastian , Zapatka Marc , Reinelt Gerhard , Eils Roland
Published: March 2006

Background

Microarray technology produces gene expression data on a genomic scale for an endless variety of organisms and conditions. However, this vast amount of information needs to be extracted in a reasonable way and funneled into manageable and functionally meaningful patterns. Genes may be reasonably combined using knowledge about their interaction behaviour. On a proteomic level, biochemical research has elucidated an increasingly complete image of the metabolic architecture, especially for less complex organisms like the well studied bacterium Escherichia coli.

Results

We sought to discover central components of the metabolic network, regulated by the expression of associated genes under changing conditions. We mapped gene expression data from E. coli under aerobic and anaerobic conditions onto the enzymatic reaction nodes of its metabolic network. An adjacency matrix of the metabolites was created from this graph. A consecutive ones clustering method was used to obtain network clusters in the matrix. The wavelet method was applied on the adjacency matrices of these clusters to collect features for the classifier. With a feature extraction method the most discriminating features were selected. We yielded network sub-graphs from these top ranking features representing formate fermentation, in good agreement with the anaerobic response of hetero-fermentative bacteria. Furthermore, we found a switch in the starting point for NAD biosynthesis, and an adaptation of the l-aspartate metabolism, in accordance with its higher abundance under anaerobic conditions.

Conclusion

We developed and tested a novel method, based on a combination of rationally chosen machine learning methods, to analyse gene expression data on the basis of interaction data, using a metabolic network of enzymes. As a case study, we applied our method to E. coli under oxygen deprived conditions and extracted physiologically relevant patterns that represent an adaptation of the cells to changing environmental conditions. In general, our concept may be transferred to network analyses on biological interaction data, when data for two comparable states of the associated nodes are made available.
Microtubules regulate disassembly of epithelial apical junctions
Authors: Ivanov Andrei I , McCall Ingrid C , Babbin Brian , Samarin Stanislav N , Nusrat Asma , Parkos Charles A
Published: March 2006

Background

Epithelial tight junction (TJ) and adherens junction (AJ) form the apical junctional complex (AJC) which regulates cell-cell adhesion, paracellular permeability and cell polarity. The AJC is anchored on cytoskeletal structures including actin microfilaments and microtubules. Such cytoskeletal interactions are thought to be important for the assembly and remodeling of apical junctions. In the present study, we investigated the role of microtubules in disassembly of the AJC in intestinal epithelial cells using a model of extracellular calcium depletion.

Results

Calcium depletion resulted in disruption and internalization of epithelial TJs and AJs along with reorganization of perijunctional F-actin into contractile rings. Microtubules reorganized into dense plaques positioned inside such F-actin rings. Depolymerization of microtubules with nocodazole prevented junctional disassembly and F-actin ring formation. Stabilization of microtubules with either docetaxel or pacitaxel blocked contraction of F-actin rings and attenuated internalization of junctional proteins into a subapical cytosolic compartment. Likewise, pharmacological inhibition of microtubule motors, kinesins, prevented contraction of F-actin rings and attenuated disassembly of apical junctions. Kinesin-1 was enriched at the AJC in cultured epithelial cells and it also accumulated at epithelial cell-cell contacts in normal human colonic mucosa. Furthermore, immunoprecipitation experiments demonstrated association of kinesin-1 with the E-cadherin-catenin complex.

Conclusion

Our data suggest that microtubules play a role in disassembly of the AJC during calcium depletion by regulating formation of contractile F-actin rings and internalization of AJ/TJ proteins.
Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region
Authors: García-Vallvé Santiago , Iglesias-Rozas José R , Alonso Ángel , Bravo Ignacio G
Published: March 2006

Background

Papillomaviruses (PVs) infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR) of the virus. It is believed that there is a core of transcription factor binding sites (TFBS) common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses.

Results

We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS.

Conclusion

There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host,i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs.
Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks
Authors: Carlson Marc RJ , Zhang Bin , Fang Zixing , Mischel Paul S , Horvath Steve , Nelson Stanley F
Published: March 2006

Background

Genes and proteins are organized into functional modular networks in which the network context of a gene or protein has implications for cellular function. Highly connected hub proteins, largely responsible for maintaining network connectivity, have been found to be much more likely to be essential for yeast survival.

Results

Here we investigate the properties of weighted gene co-expression networks formed from multiple microarray datasets. The constructed networks approximate scale-free topology, but this is not universal across all datasets. We show strong positive correlations between gene connectivity within the whole network and gene essentiality as well as gene sequence conservation. We demonstrate the preservation of a modular structure of the networks formed, and demonstrate that, within some of these modules, it is possible to observe a strong correlation between connectivity and essentiality or between connectivity and conservation within the modules particularly within modules containing larger numbers of essential genes.

Conclusion

Application of these techniques can allow a finer scale prediction of relative gene importance for a particular process within a group of similarly expressed genes.
Application of DETECTER, an evolutionary genomic tool to analyze genetic variation, to the cystic fibrosis gene family
Authors: Gaucher Eric A , De Kee Danny W , Benner Steven A
Published: March 2006

Background

The medical community requires computational tools that distinguish missense genetic differences having phenotypic impact within the vast number of sense mutations that do not. Tools that do this will become increasingly important for those seeking to use human genome sequence data to predict disease, make prognoses, and customize therapy to individual patients.

Results

An approach, termed DETECTER, is proposed to identify sites in a protein sequence where amino acid replacements are likely to have a significant effect on phenotype, including causing genetic disease. This approach uses a model-dependent tool to estimate the normalized replacement rate at individual sites in a protein sequence, based on a history of those sites extracted from an evolutionary analysis of the corresponding protein family. This tool identifies sites that have higher-than-average, average, or lower-than-average rates of change in the lineage leading to the sequence in the population of interest. The rates are then combined with sequence data to determine the likelihoods that particular amino acids were present at individual sites in the evolutionary history of the gene family. These likelihoods are used to predict whether any specific amino acid replacements, if introduced at the site in a modern human population, would have a significant impact on fitness. The DETECTER tool is used to analyze the cystic fibrosis transmembrane conductance regulator (CFTR) gene family.

Conclusion

In this system, DETECTER retrodicts amino acid replacements associated with the cystic fibrosis disease with greater accuracy than alternative approaches. While this result validates this approach for this particular family of proteins only, the approach may be applicable to the analysis of polymorphisms generally, including SNPs in a human population.
Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation
Authors: Mueller Jonathan Wolf , Kessler Daniel , Neumann Daniel , Stratmann Tina , Papatheodorou Panagiotis , Hartmann-Fatu Cristina , Bayer Peter
Published: March 2006

Background

The peptidyl prolyl cis/trans isomerase (PPIase) Parvulin (Par14/PIN4) is highly conserved in all metazoans and is assumed to play a role in cell cycle progression and chromatin remodeling. It is predominantly localized to the nucleus and binds to chromosomal DNA as well as bent oligonucleotides in vitro.

Results

In this study we confirm by RT-PCR the existence of a longer Parvulin isoform expressed in all tissues examined so far. This isoform contains a 5' extension including a 75 bp extended open reading frame with two coupled SNPs leading to amino acid substitutions Q16R and R18S. About 1% of all Parvulin mRNAs include the novel extension as quantified by real-time PCR. The human Parvulin promoter is TATA-less and situated in a CpG island typical for house keeping genes. Thus, different Parvulin mRNAs seem to arise by alternative transcription initiation. N-terminally extended Parvulin is protected from rapid proteinaseK degradation. In HeLa and HepG2 cell lysates two protein species of about 17 and 28 KDa are detected by an antibody against an epitope within the N-terminal extension. These two bands are also recognized by an antibody towards the PPIase domain of Parvulin. The longer Parvulin protein is encoded by the human genome but absent from rodent, bovine and non-mammalian genomes.

Conclusion

Due to its molecular weight of 16.6 KDa we denote the novel Parvulin isoform as Par17 following the E. coli Par10 and human Par14 nomenclature. The N-terminal elongation of Par17-QR and Par17-RS suggests these isoforms to perform divergent functions within the eukaryotic cell than the well characterized Par14.
The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality
Authors: Nieminen Tuomo , Lehtinen Rami , Viik Jari , Lehtimäki Terho , Niemelä Kari , Nikus Kjell , Niemi Mari , Kallio Janne , Kööbi Tiit , Turjanmaa Väinö , Kähönen Mika
Published: March 2006

Background

The purpose of the Finnish Cardiovascular Study (FINCAVAS) is to construct a risk profile – using genetic, haemodynamic and electrocardiographic (ECG) markers – of individuals at high risk of cardiovascular diseases, events and deaths.

Methods and design

All patients scheduled for an exercise stress test at Tampere University Hospital and willing to participate have been and will be recruited between October 2001 and December 2007. The final number of participants is estimated to reach 5,000. Technically successful data on exercise tests using a bicycle ergometer have been collected of 2,212 patients (1,400 men and 812 women) by the end of 2004. In addition to repeated measurement of heart rate and blood pressure, digital high-resolution ECG at 500 Hz is recorded continuously during the entire exercise test, including the resting and recovery phases. About 20% of the patients are examined with coronary angiography. Genetic variations known or suspected to alter cardiovascular function or pathophysiology are analysed to elucidate the effects and interactions of these candidate genes, exercise and commonly used cardiovascular medications.

Discussion

FINCAVAS compiles an extensive set of data on patient history, genetic variation, cardiovascular parameters, ECG markers as well as follow-up data on clinical events, hospitalisations and deaths. The data enables the development of new diagnostic and prognostic tools as well as assessments of the importance of existing markers.
CUSUM: A tool for early feedback about performance?
Authors: Chang Winston R , McLean Ian P
Published: March 2006

Background

Modern day clinical practice demands evidence justifying our choice of treatment methods. Cumulative sum techniques (cusum) are amongst the simplest statistical methods known. They provide rapid analysis and identification of trends in a series of data. This study highlights use of these techniques as an early performance indicator of a clinical procedure before its implementation.

Methods

Twenty consecutive patients who underwent total hip or knee arthroplasty received a simple dressing – blue gauze and Tegaderm. Cusum charting was used to assess the dressing with regards to skin blistering. At an acceptable level of performance the curve would oscillate about the horizontal axis and the overall trend therefore said to be flat. If performance is unacceptable, the cusum slopes upward.

Results

The cusum plot for the twenty patients did not cross the specified control limits. This showed that our simple dressing met specified standards with regards to wound blistering postoperatively.

Conclusion

We recommend the use of this simple, yet versatile cusum technique in the early evaluation of a clinical procedure before its implementation.
Violence in primary care: Prevalence and follow-up of victims
Authors: Morier-Genoud Claire , Bodenmann Patrick , Favrat Bernard , Vannotti Marco
Published: March 2006

Background

Primary care physicians underestimate the prevalence of domestic violence and community violence. Victims are therefore at risk of further episodes of violence, with psychological and physical consequences. We used an interview to assess the prevalence of domestic and community violence among Swiss natives and foreigners. In a follow-up study, we evaluated the consequences of the interview for the positive patients.

Methods

We evaluated the prevalence of violence by use of a questionnaire in an interview, in an academic general internal medicine clinic in Switzerland. In a follow-up, we evaluated the consequences of the interview for positive patients. The participants were 38 residents and 446 consecutive patients. Questionnaires were presented in the principal language spoken by our patients. They addressed sociodemographics, present and past violence, the security or lack of security felt by victims of violence, and the patients' own violence. Between 3 and 6 months after the first interview, we did a follow-up of all patients who had reported domestic violence in the last year.

Results

Of the 366 patients included in the study, 36 (9.8%) reported being victims of physical violence during the last year (physicians identified only 4 patients out of the 36), and 34/366 (9.3%) reported being victims of psychological violence. Domestic violence was responsible for 67.3% of the cases, and community violence for 21.8%. In 10.9% of the cases, both forms of violence were found.

Of 29 patients who reported being victims of domestic violence, 22 were found in the follow-up. The frequency of violence had diminished (4/22) or the violence had ceased (17/22).

Conclusion

The prevalence of violence is high; domestic violence is more frequent than community violence. There was no statistically significant difference between the Swiss and foreign patients' responses related to the rates of violence. Patients in a currently violent relationship stated that participating in the study helped them and that the violence decreased or ceased a few months later.
Diarrhea, CD4 counts and enteric infections in a hospital – based cohort of HIV-infected patients around Varanasi, India
Authors: Attili Suresh VS , Gulati AK , Singh VP , Varma DV , Rai M , Sundar Shyam
Published: March 2006

Background

As most of the studies in HIV patients with diarrhea were cross sectional, focusing on the etiological agents, we are reporting data on the rate of diarrhea, associations between diarrhea and CD4 counts and variation in frequency of identifying a pathogen with consistency of diarrhea and duration in a prospective hospital based study.

Methods

Stool specimens were obtained between Jan 2001 and April 2003 from HIV infected adults with diarrhea presenting to Infectious Disease clinic, Banaras Hindu University, Varanasi. In all patients with diarrhea, specimens were examined by microscopy and cultures to identify pathogens.

Results

During the study, 630 person years of observations with diarrhea were analyzed. 140 stool samples were collected representing 43% of episodes of reported diarrhea. Positivity of finding a pathogen from watery stools and formed stools were 40%&24% respectively (p < 0.01) probably due to associated inflammation is more in watery diarrhea. Patients having chronic diarrhea are 2.25 (95%CI 1.52–2.81) times at more risk of developing other opportunistic infections compared to those who don't have. However this is not true with the acute diarrhea where risk of harboring the opportunistic infections remain same.

Conclusion

Diarrhea was most strongly associated with low CD4 counts. Over two-thirds of diarrheal episodes were undiagnosed, suggesting that unidentified agents or primary HIV enteropathy are important causes of diarrhea in this population. There is a strong negative association between duration of diarrhea and CD4 levels
Digital clubbing in tuberculosis – relationship to HIV infection, extent of disease and hypoalbuminemia
Authors: Ddungu Henry , Johnson John L , Smieja Marek , Mayanja-Kizza Harriet
Published: March 2006

Background

Digital clubbing is a sign of chest disease known since the time of Hippocrates. Its association with tuberculosis (TB) has not been well studied, particularly in Africa where TB is common. The prevalence of clubbing in patients with pulmonary TB and its association with Human Immunodeficiency Virus (HIV), severity of disease, and nutritional status was assessed.

Methods

A cross-sectional study was carried out among patients with smear-positive TB recruited consecutively from the medical and TB wards and outpatient clinics at a public hospital in Uganda. The presence of clubbing was assessed by clinical signs and measurement of the ratio of the distal and inter-phalangeal diameters (DPD/IPD) of both index fingers. Clubbing was defined as a ratio > 1.0. Chest radiograph, serum albumin and HIV testing were done.

Results

Two hundred patients (82% HIV-infected) participated; 34% had clubbing by clinical criteria whilst 30% had clubbing based on DPD/IPD ratio. Smear grade, extensive or cavitary disease, early versus late HIV disease, and hypoalbuminemia were not associated with clubbing. Clubbing was more common among patients with a lower Karnofsky performance scale score or with prior TB.

Conclusion

Clubbing occurs in up to one-third of Ugandan patients with pulmonary TB. Clubbing was not associated with stage of HIV infection, extensive disease or hypoalbuminemia.
Evidence for a gene influencing heart rate on chromosome 5p13-14 in a meta-analysis of genome-wide scans from the NHLBI Family Blood Pressure Program
Authors: Laramie Jason M , Wilk Jemma B , Hunt Steven C , Ellison R Curtis , Chakravarti Aravinda , Boerwinkle Eric , Myers Richard H
Published: March 2006

Background

Elevated resting heart rate has been shown in multiple studies to be a strong predictor of cardiovascular disease. Previous family studies have shown a significant heritable component to heart rate with several groups conducting genomic linkage scans to identify quantitative trait loci.

Methods

We performed a genome-wide linkage scan to identify quantitative trait loci influencing resting heart rate among 3,282 Caucasians and 3,989 African-Americans in three independent networks comprising the Family Blood Pressure Program (FBPP) using 368 microsatellite markers. Mean heart rate measurements were used in a regression model including covariates for age, body mass index, pack-years, currently drinking alcohol (yes/no), hypertension status and medication usage to create a standardized residual for each gender/ethnic group within each study network. This residual was used in a nonparametric variance component model to generate a LOD score and a corresponding P value for each ethnic group within each study network. P values from each ethnic group and study network were merged using an adjusted Fisher's combining P values method and the resulting P values were converted to LOD scores. The entire analysis was redone after individuals currently taking beta-blocker medication were removed.

Results

We identified significant evidence of linkage (LOD = 4.62) to chromosome 10 near 142.78 cM in the Caucasian group of HyperGEN. Between race and network groups we identified a LOD score of 1.86 on chromosome 5 (between 39.99 and 45.34 cM) in African-Americans in the GENOA network and the same region produced a LOD score of 1.12 among Caucasians within a different network (HyperGEN). Combining all network and race groups we identified a LOD score of 1.92 (P = 0.0013) on chromosome 5p13-14. We assessed heterogeneity for this locus between networks and ethnic groups and found significant evidence for low heterogeneity (P ≤ 0.05).

Conclusion

We found replication (LOD > 1) between ethnic groups and between study networks with low heterogeneity on chromosome 5p13-14 suggesting that a gene in this region influences resting heart rate.
Combinatorial Mismatch Scan (CMS) for loci associated with dementia in the Amish
Authors: McCauley Jacob L , Hahs Daniel W , Jiang Lan , Scott William K , Welsh-Bohmer Kathleen A , Jackson Charles E , Vance Jeffery M , Pericak-Vance Margaret A , Haines Jonathan L
Published: March 2006

Background

Population heterogeneity may be a significant confounding factor hampering detection and verification of late onset Alzheimer's disease (LOAD) susceptibility genes. The Amish communities located in Indiana and Ohio are relatively isolated populations that may have increased power to detect disease susceptibility genes.

Methods

We recently performed a genome scan of dementia in this population that detected several potential loci. However, analyses of these data are complicated by the highly consanguineous nature of these Amish pedigrees. Therefore we applied the Combinatorial Mismatch Scanning (CMS) method that compares identity by state (IBS) (under the presumption of identity by descent (IBD)) sharing in distantly related individuals from such populations where standard linkage and association analyses are difficult to implement. CMS compares allele sharing between individuals in affected and unaffected groups from founder populations. Comparisons between cases and controls were done using two Fisher's exact tests, one testing for excess in IBS allele frequency and the other testing for excess in IBS genotype frequency for 407 microsatellite markers.

Results

In all, 13 dementia cases and 14 normal controls were identified who were not related at least through the grandparental generation. The examination of allele frequencies identified 24 markers (6%) nominally (p ≤ 0.05) associated with dementia; the most interesting (empiric p ≤ 0.005) markers were D3S1262, D5S211, and D19S1165. The examination of genotype frequencies identified 21 markers (5%) nominally (p ≤ 0.05) associated with dementia; the most significant markers were both located on chromosome 5 (D5S1480 and D5S211). Notably, one of these markers (D5S211) demonstrated differences (empiric p ≤ 0.005) under both tests.

Conclusion

Our results provide the initial groundwork for identifying genes involved in late-onset Alzheimer's disease within the Amish community. Genes identified within this isolated population will likely play a role in a subset of late-onset AD cases across more general populations. Regions highlighted by markers demonstrating suggestive allelic and/or genotypic differences will be the focus of more detailed examination to characterize their involvement in dementia.
Ascites due to right atrial myxoma in a haemodialysis patient
Authors: Banerjee Anindya , Davenport Andrew
Published: March 2006

Background

Persistent fluid overload in patients on renal replacement therapy despite good dialysis adequacy or obvious cardiac dysfunction should prompt a search for rarer causes.

Case presentation

We report here a rare cause of persistent peripheral oedema and ascites in a well-dialysed patient. CT scanning revealed a right atrial myxoma that was later confirmed on an echocardiogram.

Conclusion

Fluid overload states are common in patients on dialysis. Common causes are inadequacy of dialysis and non-compliance. Where aetiology is not easily apparent further investigations into rarer causes should be sought.
Carcinosarcoma of monoclonal origin arising in a dermoid cyst of ovary: a case report
Authors: Cabibi Daniela , Martorana Anna , Cappello Francesco , Barresi Elisa , Di Gangi Claudio , Rodolico Vito
Published: March 2006

Background

Transformation of a cystic benign teratoma of the ovary into a "carcinosarcoma" has very rarely been reported and its histogenetic origin is still debated.

Case presentation

A case of carcinosarcoma arising from a dermoid cyst is reported. The tumor showed cystic areas delimited by normal squamous epithelium, with transitional areas through dysplastic epithelium to "in situ" and infiltrating squamous cell carcinoma (SCC).

The sarcomatous component showed compact tissue composed of round cells concentrically arranged around small vessels, spindle, and pleomorphic cells with a high nuclear-cytoplasmic ratio.

Positive staining for vimentin, alpha smooth muscle actin and CD10, as well as P53 and P63, was found in the sarcomatous component and in some atypical basal cells of the squamous epithelium, which also showed the usual epithelial markers.

Conclusion

To the best of our knowledge, this is the first case of carcinosarcoma arising from a dermoid cyst in which a histogenetic origin from totipotent stem cells, located in the basal squamous layer, is supported by immunohistochemical findings.
The benefits and risks of bacille Calmette-Guérin vaccination among infants at high risk for both tuberculosis and severe combined immunodeficiency: assessment by Markov model
Authors: Clark Michael , Cameron D William
Published: March 2006

Background

Bacille Calmette-Guérin (BCG) vaccine is given to Canadian Aboriginal neonates in selected communities. Severe reactions and deaths associated with BCG have been reported among infants born with immunodeficiency syndromes. The main objective of this study was to estimate threshold values for severe combined immunodeficiency (SCID) incidence, above which BCG is associated with greater risk than benefit.

Methods

A Markov model was developed to simulate the natural histories of tuberculosis (TB) and SCID in children from birth to 14 years. The annual risk of tuberculous infection (ARI) and SCID incidence were varied in analyses. The model compared a scenario of no vaccination to intervention with BCG. Appropriate variability and uncertainty analyses were conducted. Outcomes included TB incidence and quality-adjusted life years (QALYs).

Results

In sensitivity analyses, QALYs were lower among vaccinated infants if the ARI was 0.1% and the rate of SCID was higher than 4.2 per 100,000. Assuming an ARI of 1%, this threshold increased to 41 per 100,000. In uncertainty analyses (Monte Carlo simulations) which assumed an ARI of 0.1%, QALYs were not significantly increased by BCG unless SCID incidence is 0. With this ARI, QALYs were significantly decreased among vaccinated children if SCID incidence exceeds 23 per 100,000. BCG is associated with a significant increase in QALYs if the ARI is 1%, and SCID incidence is below 5 per 100,000.

Conclusion

The possibility that Canadian Aboriginal children are at increased risk for SCID has serious implications for continued BCG use in this population. In this context, enhanced TB Control – including early detection and treatment of infection – may be a safer, more effective alternative.
A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicumin 50 irrigated and rain-fed villages in Samar Province, the Philippines
Authors: Tarafder Mushfiqur R , Balolong Ernesto , Carabin Hélène , Bélisle Patrick , Tallo Veronica , Joseph Lawrence , Alday Portia , Gonzales Ryan O'Neil , Riley Steven , Olveda Remigio , McGarvey Stephen T
Published: March 2006

Background

Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines.

Methods

This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis.

Results

A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21).

Discussion

We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants.
A family of E. coliexpression vectors for laboratory scale and high throughput soluble protein production
Authors: Cabrita Lisa D , Dai Weiwen , Bottomley Stephen P
Published: March 2006

Background

In the past few years, both automated and manual high-throughput protein expression and purification has become an accessible means to rapidly screen and produce soluble proteins for structural and functional studies. However, many of the commercial vectors encoding different solubility tags require different cloning and purification steps for each vector, considerably slowing down expression screening. We have developed a set of E. coli expression vectors with different solubility tags that allow for parallel cloning from a single PCR product and can be purified using the same protocol.

Results

The set of E. coli expression vectors, encode for either a hexa-histidine tag or the three most commonly used solubility tags (GST, MBP, NusA) and all with an N-terminal hexa-histidine sequence. The result is two-fold: the His-tag facilitates purification by immobilised metal affinity chromatography, whilst the fusion domains act primarily as solubility aids during expression, in addition to providing an optional purification step. We have also incorporated a TEV recognition sequence following the solubility tag domain, which allows for highly specific cleavage (using TEV protease) of the fusion protein to yield native protein. These vectors are also designed for ligation-independent cloning and they possess a high-level expressing T7 promoter, which is suitable for auto-induction. To validate our vector system, we have cloned four different genes and also one gene into all four vectors and used small-scale expression and purification techniques. We demonstrate that the vectors are capable of high levels of expression and that efficient screening of new proteins can be readily achieved at the laboratory level.

Conclusion

The result is a set of four rationally designed vectors, which can be used for streamlined cloning, expression and purification of target proteins in the laboratory and have the potential for being adaptable to a high-throughput screening.
Fold classification based on secondary structure – how much is gained by including loop topology?
Authors: Jeong Jieun , Berman Piotr , Przytycka Teresa
Published: March 2006

Background

It has been proposed that secondary structure information can be used to classify (to some extend) protein folds. Since this method utilizes very limited information about the protein structure, it is not surprising that it has a higher error rate than the approaches that use full 3D fold description. On the other hand, the comparing of 3D protein structures is computing intensive. This raises the question to what extend the error rate can be decreased with each new source of information, especially if the new information can still be used with simple alignment algorithms.

We consider the question whether the information about closed loops can improve the accuracy of this approach. While the answer appears to be obvious, we had to overcome two challenges. First, how to code and to compare topological information in such a way that local alignment of strings will properly identify similar structures. Second, how to properly measure the effect of new information in a large data sample.

We investigate alternative ways of computing and presenting this information.

Results

We used the set of beta proteins with at most 30% pairwise identity to test the approach; local alignment scores were used to build a tree of clusters which was evaluated using a new log-odd cluster scoring function. In particular, we derive a closed formula for the probability of obtaining a given score by chance.Parameters of local alignment function were optimized using a genetic algorithm.

Of 81 folds that had more than one representative in our data set, log-odds scores registered significantly better clustering in 27 cases and significantly worse in 6 cases, and small differences in the remaining cases. Various notions of the significant change or average change were considered and tried, and the results were all pointing in the same direction.

Conclusion

We found that, on average, properly presented information about the loop topology improves noticeably the accuracy of the method but the benefits vary between fold families as measured by log-odds cluster score.
A thyroid tumor extending to the parapharyngeal space
Authors: Cetik Fikret , Yazici Demet , Uguz Aysun
Published: March 2006

Background

The metastasis of papillary thyroid carcinoma to the parapharyngeal space is rare and discussed in the English literature before. Encountering a parapharyngeal mass with cystic appearance on imaging, one should rule out thyroid malignancy as differential diagnosis.

Case presentation

The case presented here is a 22-year-old woman who was referred to our clinic with complaints of painless neck mass, dysphagia and hoarseness for two years. After radiologic and pathological examination, the mass thought to be relevant with the thyroid gland. Peroperatively, the tumor was found to originate from the superior pole of the right thyroid gland, with a narrow stalk, and extended following the neurovascular bundle to the lower part of the parapharyngeal space. The bulk was removed via transservical approach with total thyroidectomy.

Conclusion

The occurrence of the follicular variant of papillary thyroid carcinoma in the parapharyngeal space is extremely rare. The management of this rare case was discussed with the review of literature.
Is general inpatient obstetrics and gynaecology evidence-based? A survey of practice with critical review of methodological issues
Authors: Khan Aamir T , Mehr M Nauman , Gaynor Anne-Marie , Bowcock Malcolm , Khan Khalid S
Published: March 2006

Background

To examine the rates of evidence-supported care provided in an obstetrics-gynaecology unit.

Methods

The main diagnosis-intervention set was established for a sample of 325 consecutive inpatient admissions in 1998–99 in a prospective study in a UK tertiary care centre. A comprehensive literature search was conducted to obtain the evidence supporting the intervention categorised according to the following hierarchy: Grade A, care supported by evidence from randomised controlled trials; Grade B, care supported by evidence from controlled observational studies and convincing non-randomised evidence; and Grade C, care without substantial research evidence.

Results

Of the 325 admissions, in 135 (42%) the quality of care was based on Grade A evidence, in 157 (48%) it was based on Grade B evidence, and in 33 (10%) it was based on Grade C evidence. The patterns of care were not different amongst patients sampled in 1998 and 1999.

Conclusion

A significant majority (90%) of obstetric and gynaecological care was found to be supported by substantial research evidence.
Knowledge, attitudes and practices on cervical cancer screening among the medical workers of Mulago Hospital, Uganda
Authors: Mutyaba Twaha , Mmiro Francis A , Weiderpass Elisabete
Published: March 2006

Background

Cervical cancer is the commonest cancer of women in Uganda. Over 80% of women diagnosed in Mulago national referral and teaching hospital, the biggest hospital in Uganda, have advanced disease. Pap smear screening, on opportunistic rather than systematic basis, is offered free in the gynaecological outpatients clinic and the postnatal/family planning clinics. Medical students in the third and final clerkships are expected to learn the techniques of screening. Objectives of this study were to describe knowledge on cervical cancer, attitudes and practices towards cervical cancer screening among the medical workers of Mulago hospital.

Methods

In a descriptive cross-sectional study, a weighted sample of 310 medical workers including nurses, doctors and final year medical students were interviewed using a self-administered questionnaire. We measured knowledge about cervical cancer: (risk factors, eligibility for screening and screening techniques), attitudes towards cervical cancer screening and practices regarding screening.

Results

Response rate was 92% (285). Of these, 93% considered cancer of the cervix a public health problem and knowledge about Pap smear was 83% among respondents. Less than 40% knew risk factors for cervical cancer, eligibility for and screening interval. Of the female respondents, 65% didn't feel susceptible to cervical cancer and 81% had never been screened. Of the male respondents, only 26% had partners who had ever been screened. Only 14% of the final year medical students felt skilled enough to use a vaginal speculum and 87% had never performed a pap smear.

Conclusion

Despite knowledge of the gravity of cervical cancer and prevention by screening using a Pap smear, attitudes and practices towards screening were negative. The medical workers who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. There is need to explain/understand the cause of these attitudes and practices and identify possible interventions to change them. Medical students leave medical school without adequate skills to be able to effectively screen women for cervical cancer wherever they go to practice. Medical students and nurses training curricula needs review to incorporate practical skills on cervical cancer screening.
A critical evaluation of the electronic surgical logbook
Authors: Achuthan R , Grover K , MacFie J
Published: March 2006

Background

The Association of Surgeons of Great Britain and Ireland (ASGBI) devised the electronic surgical logbook (version 2.4) for higher trainees in General Surgery enabling trainees to compile a uniform data set of their operative and training experience. This is in use by higher surgical trainees (HST) in the United Kingdom. This logbook permits trainees to submit data centrally into a Regional Analysis Database (RAD). With the implementation of the European Working Time Directive (EWTD) there is need for reliable data to assess the effects of the directive on training. In order to draw meaningful conclusions from the database the quality of data needs to be validated. We critically analysed the RAD in the Yorkshire region for a one-year period.

Methods

The RAD from the ASGBI for the Yorkshire region was analysed. Data for the period 01/10/2002–30/09/2003 was identified and interrogated using Microsoft Excel (2000 version). The RAD was compared with information obtained from the Regional Surgical Advisor for Yorkshire with respect to hospitals, surgical consultants and HST's in the region during the study period.

Results

There were 13,755 operations entered for the study period. 579 corrections to the data had to be made (4.2%) and a further 1140 entries were deleted (8.2%). Following corrections and deletions 12,615 operative entries were available for analysis. Overall 12.5% of the data required either correction or exclusion from the database prior to analysis.

Conclusion

The RAD has a large dataset useful to monitor and assess training. However, the quality of the data needs to be verified prior to use. Recommendations have been made to develop the ASGBI logbook, which would eventually translate to improved data reliability of the RAD.
Parameter selection for and implementation of a web-based decision-support tool to predict extubation outcome in premature infants
Authors: Mueller Martina , Wagner Carol L , Annibale David J , Knapp Rebecca G , Hulsey Thomas C , Almeida Jonas S
Published: March 2006

Background

Approximately 30% of intubated preterm infants with respiratory distress syndrome (RDS) will fail attempted extubation, requiring reintubation and mechanical ventilation. Although ventilator technology and monitoring of premature infants have improved over time, optimal extubation remains challenging. Furthermore, extubation decisions for premature infants require complex informational processing, techniques implicitly learned through clinical practice. Computer-aided decision-support tools would benefit inexperienced clinicians, especially during peak neonatal intensive care unit (NICU) census.

Methods

A five-step procedure was developed to identify predictive variables. Clinical expert (CE) thought processes comprised one model. Variables from that model were used to develop two mathematical models for the decision-support tool: an artificial neural network (ANN) and a multivariate logistic regression model (MLR). The ranking of the variables in the three models was compared using the Wilcoxon Signed Rank Test. The best performing model was used in a web-based decision-support tool with a user interface implemented in Hypertext Markup Language (HTML) and the mathematical model employing the ANN.

Results

CEs identified 51 potentially predictive variables for extubation decisions for an infant on mechanical ventilation. Comparisons of the three models showed a significant difference between the ANN and the CE (p = 0.0006). Of the original 51 potentially predictive variables, the 13 most predictive variables were used to develop an ANN as a web-based decision-tool. The ANN processes user-provided data and returns the prediction 0–1 score and a novelty index. The user then selects the most appropriate threshold for categorizing the prediction as a success or failure. Furthermore, the novelty index, indicating the similarity of the test case to the training case, allows the user to assess the confidence level of the prediction with regard to how much the new data differ from the data originally used for the development of the prediction tool.

Conclusion

State-of-the-art, machine-learning methods can be employed for the development of sophisticated tools to aid clinicians' decisions. We identified numerous variables considered relevant for extubation decisions for mechanically ventilated premature infants with RDS. We then developed a web-based decision-support tool for clinicians which can be made widely available and potentially improve patient care world wide.
Seasonality of service provision in hip and knee surgery: A possible contributor to waiting times? A time series analysis
Authors: Upshur Ross EG , Moineddin Rahim , Crighton Eric J , Mamdani Muhammad
Published: March 2006

Background

The question of how best to reduce waiting times for health care, particularly surgical procedures such as hip and knee replacements is among the most pressing concern of the Canadian health care system. The objective of this study was to test the hypothesis that significant seasonal variation exists in the performance of hip and knee replacement surgery in the province of Ontario.

Methods

We performed a retrospective, cross-sectional time series analysis examining all hip and knee replacement surgeries in people over the age of 65 in the province of Ontario, Canada between 1992 and 2002. The main outcome measure was monthly hospitalization rates per 100 000 population for all hip and knee replacements.

Results

There was a marked increase in the rate of hip and knee replacement surgery over the 10-year period as well as an increasing seasonal variation in surgeries. Highly significant (Fisher Kappa = 16.05, p < 0.01; Bartlett-Kolmogorov-Smirnov Test = 0.31, p < 0.01) and strong (R2
Autoreg = 0.85) seasonality was identified in the data.

Conclusion

Holidays and utilization caps appear to exert a significant influence on the rate of service provision. It is expected that waiting times for hip and knee replacement could be reduced by reducing seasonal fluctuations in service provision and benchmarking services to peak delivery. The results highlight the importance of system behaviour in seasonal fluctuation of service delivery.