bluuebunny/crossref_metadata_2025 huggingface dataset:
BAMarray™: Java software for Bayesian analysis of variance for microarray data
Authors: Ishwaran Hemant , Rao J Sunil , Kogalur Udaya B
Published: February 2006

Background

DNA microarrays open up a new horizon for studying the genetic determinants of disease. The high throughput nature of these arrays creates an enormous wealth of information, but also poses a challenge to data analysis. Inferential problems become even more pronounced as experimental designs used to collect data become more complex. An important example ismultigroup datacollected over different experimental groups, such as data collected from distinct stages of a disease process. We have developed a method specifically addressing these issues termed Bayesian ANOVA for microarrays (BAM). The BAM approach uses a special inferential regularization known as spike-and-slab shrinkage that provides an optimal balance between total false detections and total false non-detections. This translates into more reproducible differential calls. Spike and slab shrinkage is a form of regularization achieved by using information across all genes and groups simultaneously.

Results

BAMarray™ is a graphically oriented Java-based software package that implements the BAM method for detecting differentially expressing genes in multigroup microarray experiments (up to 256 experimental groups can be analyzed). Drop-down menus allow the user to easily select between different models and to choose various run options. BAMarray™ can also be operated in a fully automated mode with preselected run options. Tuning parameters have been preset at theoretically optimal values freeing the user from such specifications. BAMarray™ provides estimates for gene differential effects and automatically estimates data adaptive, optimal cutoff values for classifying genes into biological patterns of differential activity across experimental groups. A graphical suite is a core feature of the product and includes diagnostic plots for assessing model assumptions and interactive plots that enable tracking of prespecified gene lists to study such things as biological pathway perturbations. The user can zoom in and lasso genes of interest that can then be saved for downstream analyses.

Conclusion

BAMarray™ is user friendly platform independent software that effectively and efficiently implements the BAM methodology. Classifying patterns of differential activity is greatly facilitated by a data adaptive cutoff rule and a graphical suite. BAMarray™ is licensed software freely available to academic institutions. More information can be found athttp://www.bamarray.com.
JLIN: A java based linkage disequilibrium plotter
Authors: Carter Kim W , McCaskie Pamela A , Palmer Lyle J
Published: February 2006

Background

A great deal of effort and expense are being expended internationally in attempts to detect genetic polymorphisms contributing to susceptibility to complex human disease. Techniques such as Linkage Disequilibrium mapping are being increasingly used to examine and compare markers across increasingly large datasets. Visualisation techniques are becoming essential to analyse the ever-growing volume of data and results available with any given analysis.

Results

JLIN (Java LINkage disequilibrium plotter) is a software package designed for customisable, intuitive visualisation of Linkage Disequilibrium (LD) across all common computing platforms. Customisation allows the user to choose particular visualisations, statistical measures and measurement ranges. JLIN also allows the user to export images of the LD visualisation in several common document formats.

Conclusion

JLIN allows the user to visually compare and contrast the results of a range of statistical measures on the input dataset(s). These measures include the commonly used D' and r2 statistics and empirical p-values. JLIN has a number of unique and novel features that improve on existing LD visualisation tools.
Gene prediction in eukaryotes with a generalized hidden Markov model that uses hints from external sources
Authors: Stanke Mario , Schöffmann Oliver , Morgenstern Burkhard , Waack Stephan
Published: February 2006

Background

In order to improve gene prediction, extrinsic evidence on the gene structure can be collected from various sources of information such as genome-genome comparisons and EST and protein alignments. However, such evidence is often incomplete and usually uncertain. The extrinsic evidence is usually not sufficient to recover the complete gene structure of all genes completely and the available evidence is often unreliable. Therefore extrinsic evidence is most valuable when it is balanced with sequence-intrinsic evidence.

Results

We present a fairly general method for integration of external information. Our method is based on the evaluation of hints to potentially protein-coding regions by means of a Generalized Hidden Markov Model (GHMM) that takes both intrinsic and extrinsic information into account. We used this method to extend the ab initio gene prediction program AUGUSTUS to a versatile tool that we call AUGUSTUS+. In this study, we focus on hints derived from matches to an EST or protein database, but our approach can be used to include arbitrary user-defined hints. Our method is only moderately effected by the length of a database match. Further, it exploits the information that can be derived from the absence of such matches. As a special case, AUGUSTUS+ can predict genes under user-defined constraints, e.g. if the positions of certain exons are known. With hints from EST and protein databases, our new approach was able to predict 89% of the exons in human chromosome 22 correctly.

Conclusion

Sensitive probabilistic modeling of extrinsic evidence such as sequence database matches can increase gene prediction accuracy. When a match of a sequence interval to an EST or protein sequence is used it should be treated as compound information rather than as information about individual positions.
Polyphyly of the hawk genera Leucopternis and Buteogallus (Aves, Accipitridae): multiple habitat shifts during the Neotropical buteonine diversification
Authors: do Amaral Fabio S Raposo , Miller Matthew J , Silveira Luís Fábio , Bermingham Eldredge , Wajntal Anita
Published: February 2006

Background

The family Accipitridae (hawks, eagles and Old World vultures) represents a large radiation of predatory birds with an almost global distribution, although most species of this family occur in the Neotropics. Despite great morphological and ecological diversity, the evolutionary relationships in the family have been poorly explored at all taxonomic levels. Using sequences from four mitochondrial genes (12S, ATP8, ATP6, and ND6), we reconstructed the phylogeny of the Neotropical forest hawk genusLeucopternisand most of the allied genera of Neotropical buteonines. Our goals were to infer the evolutionary relationships among species ofLeucopternis, estimate their relationships to other buteonine genera, evaluate the phylogenetic significance of the white and black plumage patterns common to mostLeucopternisspecies, and assess general patterns of diversification of the group with respect to species' affiliations with Neotropical regions and habitats.

Results

Our molecular phylogeny for the genusLeucopternisand its allies disagrees sharply with traditional taxonomic arrangements for the group, and we present new hypotheses of relationships for a number of species. The mtDNA phylogenetic trees derived from analysis of the combined data posit a polyphyletic relationship among species ofLeucopternis,ButeogallusandButeo. Three highly supported clades containingLeucopternisspecies were recovered in our phylogenetic reconstructions. The first clade consisted of the sister pairsL. lacernulatusandButeogallus meridionalis, andButeogallus urubitingaandHarpyhaliaetus coronatus, in addition toL. schistaceusandL. plumbeus. The second clade included the sister pairLeucopternis albicollisandL. occidentalisas well asL. polionotus. The third lineage comprised the sister pairL. melanopsandL. kuhli, in addition toL. semiplumbeusandButeo buteo. According to our results, the white and black plumage patterns have evolved at least twice in the group. Furthermore, species found to the east and west of the Andes (cis-Andean andtrans-Andean, respectively) are not reciprocally monophyletic, nor are forest and non-forest species.

Conclusion

The polyphyly ofLeucopternis,ButeogallusandButeoestablishes a lack of concordance of current Accipitridae taxonomy with the mtDNA phylogeny for the group, and points to the need for further phylogenetic analysis at all taxonomic levels in the family as also suggested by other recent analyses. Habitat shifts, as well ascis-andtrans-Andean disjunctions, took place more than once during buteonine diversification in the Neotropical region. Overemphasis of the black and white plumage patterns has led to questionable conclusions regarding the relationships ofLeucopternisspecies, and suggests more generally that plumage characters should be used with considerable caution in the taxonomic evaluation of the Accipitridae.
Comparison of marker types and map assumptions using Markov chain Monte Carlo-based linkage analysis of COGA data
Authors: Sieh Weiva , Basu Saonli , Fu Audrey Q , Rothstein Joseph H , Scheet Paul A , Stewart William CL , Sung Yun J , Thompson Elizabeth A , Wijsman Ellen M
Published: February 2006

We performed multipoint linkage analysis of the electrophysiological trait ECB21 on chromosome 4 in the full pedigrees provided by the Collaborative Study on the Genetics of Alcoholism (COGA). Three Markov chain Monte Carlo (MCMC)-based approaches were applied to the provided and re-estimated genetic maps and to five different marker panels consisting of microsatellite (STRP) and/or SNP markers at various densities. We found evidence of linkage near the GABRB1 STRP using all methods, maps, and marker panels. Difficulties encountered with SNP panels included convergence problems and demanding computations.
Using mixture models to characterize disease-related traits
Authors: Duan Tao , Finch Stephen J , Ye Kenny Q , Chase Gary A , Mendell Nancy R
Published: February 2006

We consider 12 event-related potentials and one electroencephalogram measure as disease-related traits to compare alcohol-dependent individuals (cases) to unaffected individuals (controls). We use two approaches: 1) two-way analysis of variance (with sex and alcohol dependency as the factors), and 2) likelihood ratio tests comparing sex adjusted values of cases to controls assuming that within each group the trait has a 2 (or 3) component normal mixture distribution. In the second approach, we test the null hypothesis that the parameters of the mixtures are equal for the cases and controls. Based on the two-way analysis of variance, we find 1) males have significantly (p< 0.05) lower mean response values than females for 7 of these traits. 2) Alcohol-dependent cases have significantly lower mean response than controls for 3 traits. The mixture analysis of sex-adjusted values of 1 of these traits, the event-related potential obtained at the parietal midline channel (ttth4), found the appearance of a 3-component normal mixture in cases and controls. The mixtures differed in that the cases had significantly lower mean values than controls and significantly different mixing proportions in 2 of the 3 components. Implications of this study are: 1) Sex needs to be taken into account when studying risk factors for alcohol dependency to prevent finding a spurious association between alcohol dependency and the risk factor. 2) Mixture analysis indicates that for the event-related potential "ttth4", the difference observed reflects strong evidence of heterogeneity of response in both the cases and controls.
Many genes in fish have species-specific asymmetric rates of molecular evolution
Authors: Steinke Dirk , Salzburger Walter , Braasch Ingo , Meyer Axel
Published: February 2006

Background

Gene and genome duplication events increase the amount of genetic material that might then contribute to an increase in the genomic and phenotypic complexity of organisms during evolution. Thus, it has been argued that there is a relationship between gene copy number and morphological complexity and/or species diversity. This hypothesis implies that duplicated genes have subdivided or evolved novel functions compared to their pre-duplication proto-orthologs. Such a functional divergence might be caused by an increase in evolutionary rates in one ortholog, by changes in expression, regulatory evolution, insertion of repetitive elements, or due to positive Darwinian selection in one copy. We studied a set of 2466 genes that were present in Danio rerio, Takifugu rubripes, Tetraodon nigroviridis and Oryzias latipes to test (i) for forces of positive Darwinian selection; (ii) how frequently duplicated genes are retained, and (iii) whether novel gene functions might have evolved.

Results

25% (610) of all investigated genes show significantly smaller or higher genetic distances in the genomes of particular fish species compared to their human ortholog than their orthologs in other fish according to relative rate tests. We identified 49 new paralogous pairs of duplicated genes in fish, in which one of the paralogs is under positive Darwinian selection and shows a significantly higher rate of molecular evolution in one of the four fish species, whereas the other copy apparently did not undergo adaptive changes since it retained the original rate of evolution. Among the genes under positive Darwinian selection, we found a surprisingly high number of ATP binding proteins and transcription factors.

Conclusion

The significant rate difference suggests that the function of these rate-changed genes might be essential for the respective fish species. We demonstrate that the measurement of positive selection is a powerful tool to identify divergence rates of duplicated genes and that this method has the capacity to identify potentially interesting candidates for adaptive gene evolution.
Acceleration of epithelial cell syndecan-1 shedding by anthrax hemolytic virulence factors
Authors: Popova Taissia G , Millis Bryan , Bradburne Chris , Nazarenko Svetlana , Bailey Charles , Chandhoke Vikas , Popov Serguei G
Published: February 2006

Background

It has been recently reported that major pathogensStaphylococcus aureusandPseudomonas aeruginosaaccelerate a normal process of cell surface syndecan-1 (Synd1) ectodomain shedding as a mechanism of host damage due to the production of shedding-inducing virulence factors. We tested if acceleration of Synd1 shedding takes placein vitroupon treatment of epithelial cells withB. anthracishemolysins, as well asin vivoduring anthrax infection in mice.

Results

The isolated anthrax hemolytic proteins AnlB (sphingomyelinase) and AnlO (cholesterol-binding pore-forming factor), as well as ClnA (B. cereushomolog ofB. anthracisphosphatidyl choline-preferring phospholipase C) cause accelerated shedding of Synd1 and E-cadherin from epithelial cells and compromise epithelial barrier integrity within a few hours. In comparison with hemolysins in a similar range of concentrations, anthrax lethal toxin (LT) also accelerates shedding albeit at slower rate. Individual components of LT, lethal factor and protective antigen are inactive with regard to shedding. Inhibition experiments favor a hypothesis that activities of tested bacterial shedding inducers converge on the stimulation of cytoplasmic tyrosine kinases of the Syk family, ultimately leading to activation of cellular sheddase. Both LT and AnlO modulate ERK1/2 and p38 MAPK signaling pathways, while JNK pathway seems to be irrelevant to accelerated shedding. Accelerated shedding of Synd1 also takes place in DBA/2 mice challenged withBacillus anthracis(Sterne) spores. Elevated levels of shed ectodomain are readily detectable in circulation after 24 h.

Conclusion

The concerted acceleration of shedding by several virulence factors could represent a new pathogenic mechanism contributing to disruption of epithelial or endothelial integrity, hemorrhage, edema and abnormal cell signaling during anthrax infection.
An extremely rich repertoire of bursting patterns during the development of cortical cultures
Authors: Wagenaar Daniel A , Pine Jerome , Potter Steve M
Published: February 2006

Background

We have collected a comprehensive set of multi-unit data on dissociated cortical cultures. Previous studies of the development of the electrical activity of dissociated cultures of cortical neurons each focused on limited aspects of its dynamics, and were often based on small numbers of observed cultures. We followed 58 cultures of different densities – 3000 to 50,000 neurons on areas of 30 to 75 mm2 – growing on multi-electrode arrays (MEAs) during the first five weeks of their development.

Results

Plating density had a profound effect on development. While the aggregate spike detection rate scaled linearly with density, as expected from the number of cells in proximity to electrodes, dense cultures started to exhibit bursting behavior earlier in development than sparser cultures. Analysis of responses to electrical stimulation suggests that axonal outgrowth likewise occurred faster in dense cultures. After two weeks, the network activity was dominated by population bursts in most cultures. In contrast to previous reports, development continued with changing burst patterns throughout the observation period. Burst patterns were extremely varied, with inter-burst intervals between 1 and 300 s, different amounts of temporal clustering of bursts, and different firing rate profiles during bursts. During certain stages of development bursts were organized into tight clusters with highly conserved internal structure.

Conclusion

Dissociated cultures of cortical cells exhibited a much richer repertoire of activity patterns than previously reported. Except for the very sparsest cultures, all cultures exhibited globally synchronized bursts, but bursting patterns changed over the course of development, and varied considerably between preparations. This emphasizes the importance of using multiple preparations – not just multiple cultures from one preparation – in any study involving neuronal cultures.

These results are based on 963 half-hour-long recordings. To encourage further investigation of the rich range of behaviors exhibited by cortical cells in vitro, we are making the data available to other researchers, together with Matlab code to facilitate access.
The initial Mayo Clinic experience using high-frequency oscillatory ventilation for adult patients: a retrospective study
Authors: Finkielman Javier D , Gajic Ognjen , Farmer J Christopher , Afessa Bekele , Hubmayr Rolf D
Published: February 2006

Background

High-frequency oscillatory ventilation (HFOV) was introduced in our institution in June 2003. Since then, there has been no protocol to guide the use of HFOV, and all decisions regarding ventilation strategies and settings of HFOV were made by the treating intensivist. The aim of this study is to report our first year of experience using HFOV.

Methods

In this retrospective study, we reviewed all 14 adult patients, who were consecutively ventilated with HFOV in the intensive care units of a tertiary medical center, from June 2003 to July 2004.

Results

The mean age of the patients was 56 years, 10 were males, and all were whites. The first day median APACHE II score and its predicted hospital mortality were 35 and 83%, respectively, and the median SOFA score was 11.5. Eleven patients had ARDS, two unilateral pneumonia with septic shock, and one pulmonary edema. Patients received conventional ventilation for a median of 1.8 days before HFOV. HFOV was used 16 times for a median of 3.2 days. Improvements in oxygenation parameters were observed after 24 hours of HFOV (mean PaO2/FIO2increased from 82 to 107,P< 0.05; and the mean oxygenation index decreased from 42 to 29;P< 0.05). In two patients HFOV was discontinued, in one because of equipment failure and in another because of severe hypotension that was unresponsive to fluids. No change in mean arterial pressure, or vasopressor requirements was noted after the initiation of HFOV. Eight patients died (57 %, 95% CI: 33–79); life support was withdrawn in six and two suffered cardiac arrest.

Conclusion

During our first year of experience, HFOV was used as a rescue therapy in very sick patients with refractory hypoxemia, and improvement in oxygenation was observed after 24 hours of this technique. HFOV is a reasonable alternative when a protective lung strategy could not be achieved on conventional ventilation.
Cross-sectional relationship between physical fitness components and functional performance in older persons living in long-term care facilities
Authors: Singh Amika S , Chin A Paw Marijke JM , Bosscher Ruud J , van Mechelen Willem
Published: February 2006

Background

The age-related deterioration of physiological capacities such as muscle strength and balance is associated with increased dependence. Understanding the contribution of physical fitness components to functional performance facilitates the development of adequate exercise interventions aiming at preservation of function and independence of older people. The aim of the study was to investigate the relationship between physical fitness components and functional performance in older people living in long-term care facilities.

Methods

Designcross-sectional study

Subjects226 persons living in long-term care facilities (mean age: 81.6 ± 5.6).

Outcome measuresPhysical fitness and functional performance were measured by performance-based tests.

Results

Knee and elbow extension strength were significantly higher in men (difference = 44.5 and 50.0 N, respectively), whereas women were more flexible (difference sit & reach test = 7.2 cm). Functional performance was not significantly different between the genders. In men, motor coordination (eye-hand coordination) and measures of strength were the main contributors to functional performance, whereas in women flexibility (sit and reach test) and motor coordination (tandem stance and eye-hand coordination) played a major role.

Conclusion

The results of this study show that besides muscle strength, fitness components such as coordination and flexibility are associated with functional performance of older people living in long-term care facilities.

This suggests that men and women living in long-term care facilities, differ considerably concerning the fitness factors contributing to functional performance. Women and men may, therefore, need exercise programs emphasizing different fitness aspects in order to improve functional performance.
Increasing illness severity in very low birth weight infants over a 9-year period
Authors: Paul David A , Leef Kathleen H , Locke Robert G , Bartoshesky Louis , Walrath Judy , Stefano John L
Published: February 2006

Background

Recent reports have documented a leveling-off of survival rates in preterm infants through the 1990's. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH.

Methods

Cohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993–2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1stday of life, and total thyroxine (T4), measured on the 5thday of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis.

Results

Illness severity, as measured by SNAP and T4,increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57–116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993–1996) to 5.3/1000 (1999–2002, p = .01) over the course of the study.

Conclusion

These data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit.
Indicators of breast cancer severity and appropriateness of surgery based on hospital administrative data in the Lazio Region, Italy
Authors: Schifano Patrizia , Papini Paolo , Agabiti Nera , Scarinci Marina , Borgia Piero , Perucci Carlo A
Published: February 2006

Background

Administrative data can serve as an easily available source for epidemiological and evaluation studies. The aim of this study is to evaluate the use of hospital administrative data to determine breast cancer severity and the appropriateness of surgical treatment.

Methods

the study population consisted of 398 patients randomly selected from a cohort of women hospitalized for first-time breast cancer surgery in the Lazio Region, Italy. Tumor severity was defined in three different ways: 1) tumor size; 2) clinical stage (TNM); 3) severity indicator based on HIS data (SI). Sensitivity, specificity, and positive predictive value (PPV) of the severity indicator in evaluating appropriateness of surgery were calculated. The accuracy of HIS data was measured using Kappa statistic.

Results

Most of 387 cases were classified as T1 and T2 (tumor size), more than 70% were in stage I or II and the SI classified 60% of cases in medium-low category. Variation from guidelines indications identified under and over treatments. The accuracy of the SI to predict under-treatment was relatively good (58% of all procedures classified as under-treatment using pT where also classified as such using SI), and even greater predicting over-treatment (88.2% of all procedures classified as over treatment using pT where also classified as such using SI). Agreement between clinical chart and hospital discharge reports was K = 0.35.

Conclusion

Our findings suggest that administrative data need to be used with caution when evaluating surgical appropriateness, mainly because of the limited ability of SI to predict tumor size and the questionable quality of HIS data as observed in other studies.
The 18 Household Food Security Survey items provide valid food security classifications for adults and children in the Caribbean
Authors: Gulliford Martin C , Nunes Cheryl , Rocke Brian
Published: February 2006

Background

We tested the properties of the 18 Household Food Security Survey (HFSS) items, and the validity of the resulting food security classifications, in an English-speaking middle-income country.

Methods

Survey of primary school children in Trinidad and Tobago. Parents completed the HFSS. Responses were analysed for the 10 adult-referenced items and the eight child-referenced items. Item response theory models were fitted. Item calibrations and subject scores from a one-parameter logistic (1PL) model were compared with those from either two-parameter logistic model (2PL) or a model for differential item functioning (DIF) by ethnicity.

Results

There were 5219 eligible with 3858 (74%) completing at least one food security item. Adult item calibrations (standard error) in the 1PL model ranged from -4.082 (0.019) for the 'worried food would run out' item to 3.023 (0.042) for 'adults often do not eat for a whole day'. Child item calibrations ranged from -3.715 (0.025) for 'relied on a few kinds of low cost food' to 3.088 (0.039) for 'child didn't eat for a whole day'. Fitting either a 2PL model, which allowed discrimination parameters to vary between items, or a differential item functioning model, which allowed item calibrations to vary between ethnic groups, had little influence on interpretation. The classification based on the adult-referenced items showed that there were 19% of respondents who were food insecure without hunger, 10% food insecure with moderate hunger and 6% food insecure with severe hunger. The classification based on the child-referenced items showed that there were 23% of children who were food insecure without hunger and 9% food insecure with hunger. In both children and adults food insecurity showed a strong, graded association with lower monthly household income (P < 0.001).

Conclusion

These results support the use of 18 HFSS items to classify food security status of adults or children in an English-speaking country where food insecurity and hunger are more frequent overall than in the US.
Barriers and incentives to orphan care in a time of AIDS and economic crisis: a cross-sectional survey of caregivers in rural Zimbabwe
Authors: Howard Brian H , Phillips Carl V , Matinhure Nelia , Goodman Karen J , McCurdy Sheryl A , Johnson Cary A
Published: February 2006

Background

Africa is in an orphan-care crisis. In Zimbabwe, where one-fourth of adults are HIV-positive and one-fifth of children are orphans, AIDS and economic decline are straining society's ability to care for orphans within their extended families. Lack of stable care is putting thousands of children at heightened risk of malnourishment, emotional underdevelopment, illiteracy, poverty, sexual exploitation, and HIV infection, endangering the future health of the society they are expected to sustain.

Methods

To explore barriers and possible incentives to orphan care, a quantitative cross-sectional survey in rural eastern Zimbabwe asked 371 adults caring for children, including 212 caring for double orphans, about their well-being, needs, resources, and perceptions and experiences of orphan care.

Results

Survey responses indicate that: 1) foster caregivers are disproportionately female, older, poor, and without a spouse; 2) 98% of non-foster caregivers are willing to foster orphans, many from outside their kinship network; 3) poverty is the primary barrier to fostering; 4) financial, physical, and emotional stress levels are high among current and potential fosterers; 5) financial need may be greatest in single-orphan AIDS-impoverished households; and 6) struggling families lack external support.

Conclusion

Incentives for sustainable orphan care should focus on financial assistance, starting with free schooling, and development of community mechanisms to identify and support children in need, to evaluate and strengthen families' capacity to provide orphan care, and to initiate and support placement outside the family when necessary.
Can inhaled fluticasone alone or in combination with salmeterol reduce systemic inflammation in chronic obstructive pulmonary disease? – study protocol for a randomized controlled trial [NCT00120978]
Authors: Sin Don D , Man SF Paul , Marciniuk Darcy D , Ford Gordon , FitzGerald Mark , Wong Eric , York Ernest , Mainra Rajesh R , Ramesh Warren , Melenka Lyle S , Wilde Eric , Cowie Robert L , Williams Dave , Rousseau Roxanne ,   the ABC (Advair, Biomarkers in COPD) Investigators
Published: February 2006

Background

Systemic inflammation is associated with various complications in chronic obstructive pulmonary disease including weight loss, cachexia, osteoporosis, cancer and cardiovascular diseases. Inhaled corticosteroids attenuate airway inflammation, reduce exacerbations, and improve mortality in chronic obstructive pulmonary disease. Whether inhaled corticosteroids by themselves or in combination with a long-acting β2-adrenoceptor agonist repress systemic inflammation in chronic obstructive pulmonary disease is unknown. The Advair Biomarkers in COPD (ABC) study will determine whether the effects of inhaled corticosteroids alone or in combination with a long-acting β2-adrenoceptor agonist reduce systemic inflammation and improve health status in patients with chronic obstructive pulmonary disease.

Methods/Design

After a 4-week run-in phase during which patients with stable chronic obstructive pulmonary disease will receive inhaled fluticasone (500 micrograms twice daily), followed by a 4-week withdrawal phase during which all inhaled corticosteroids and long acting β2-adrenoceptor agonists will be discontinued, patients will be randomized to receive fluticasone (500 micrograms twice daily), fluticasone/salmeterol combination (500/50 micrograms twice daily), or placebo for four weeks. The study will recruit 250 patients across 11 centers in western Canada. Patients must be 40 years of age or older with at least 10 pack-year smoking history and have chronic obstructive pulmonary disease defined as forced expiratory volume in one second to vital capacity ratio of 0.70 or less and forced expiratory volume in one second that is 80% of predicted or less. Patients will be excluded if they have any known chronic systemic infections, inflammatory conditions, history of previous solid organ transplantation, myocardial infarction, or cerebrovascular accident within the past 3 months prior to study enrolment. The primary end-point is serum C-reactive protein level. Secondary end-points include circulating inflammatory cytokines such as interleukin-6 and interleukin-8 as well as health-related quality of life and lung function.

Discussion

If inhaled corticosteroids by themselves or in combination with a long-acting β2-adrenoceptor agonist could repress systemic inflammation, they might greatly improve clinical prognosis by reducing various complications in chronic obstructive pulmonary disease.
Preliminary report of a gas conditioner to improve operational reliability of cryotherapy in developing countries
Authors: Seamans Yancy , Sellors John , Broekhuizen Fredrik , Howard Michelle
Published: February 2006

Background

Cryotherapy is a safe, affordable, and effective method of treatment for cervical intraepithelial neoplasia. In some low-resource settings, environmental conditions or qualities of the refrigerant gas can lead to blockage of cryotherapy equipment, terminating treatment. A prototype of a gas conditioner to prevent operational failure was designed, built, and field tested.

Methods

The prototype conditioner device consists of an expansion chamber that filters and dries the refrigerant gas. Users in Peru and Kenya reported on their experience with the prototype conditioner. In Ghana, simulated cryotherapy procedures were used to test the effects of the prototype conditioner, as well as the commonly used "cough technique."

Results

Anecdotal reports from field use of the device were favorable. During simulated cryotherapy, the prevalence of blockage during freezing were 0% (0/25) with the device alone, 23.3% (7/30) with the cough technique alone, 5.9% (1/17) with both, and 55.2% (16/29) with neither (Pearson's Chi square = 26.6, df = 3, p < 0.001 (comparison amongst all groups)).

Conclusion

This prototype design of a cryotherapy gas conditioner is a potential solution for low-resource settings that are experiencing cryotherapy device malfunction.
Effectiveness of skills-based training using the Drink-less package to increase family practitioner confidence in intervening for alcohol use disorders
Authors: Proude Elizabeth M , Conigrave Katherine M , Haber Paul S
Published: February 2006

Background

Misuse of alcohol is second only to tobacco as a leading cause of preventable death in Australia. There is an opportunity in family practice to detect problems and intervene with people at risk of alcohol-related harm before complications occur. However, family practitioners (FPs) report low levels of confidence in managing patients with drinking problems. The aim of this study was to determine whether the interactive training session using the 'Drink-less' package led to improvement in FPs' self-reported level of confidence in detecting and providing interventions for risky alcohol consumption.

Method

FPs in urban and rural New South Wales were invited to training sessions in their local area. An introductory overview preceded a practical skills- based session, using the Drink-less package. Participants completed before and after evaluation forms.

Results

While 49% (CI 43 – 55) of the attending FPs indicated at baseline that they felt confident in identifying at-risk drinkers, this proportion rose to 90% (95% CI: 87 – 93) post-session, and they also reported increases in confidence from 36% (95% CI: 31 – 41) to 90% in their ability to advise patients. Urban FPs reported lower levels of confidence than rural FPs, both pre- and post-session.

Conclusion

Training sessions in the Drink-less intervention resulted in increased self-reported confidence in detection and brief intervention for alcohol problems. Further research is needed to determine the duration of this effect and its influence on practice behaviour.
A MEDLINE categorization algorithm
Authors: Darmoni Stefan J , Névéol Aurelie , Renard Jean-Marie , Gehanno Jean-Francois , Soualmia Lina F , Dahamna Badisse , Thirion Benoit
Published: February 2006

Background

Categorization is designed to enhance resource description by organizing content description so as to enable the reader to grasp quickly and easily what are the main topics discussed in it. The objective of this work is to propose a categorization algorithm to classify a set of scientific articles indexed with the MeSH thesaurus, and in particular those of the MEDLINE bibliographic database. In a large bibliographic database such as MEDLINE, finding materials of particular interest to a specialty group, or relevant to a particular audience, can be difficult. The categorization refines the retrieval of indexed material. In the CISMeF terminology, metaterms can be considered as super-concepts. They were primarily conceived to improve recall in the CISMeF quality-controlled health gateway.

Methods

The MEDLINE categorization algorithm (MCA) is based on semantic links existing between MeSH terms and metaterms on the one hand and between MeSH subheadings and metaterms on the other hand. These links are used to automatically infer a list of metaterms from any MeSH term/subheading indexing. Medical librarians manually select the semantic links.

Results

The MEDLINE categorization algorithm lists the medical specialties relevant to a MEDLINE file by decreasing order of their importance. The MEDLINE categorization algorithm is available on a Web site. It can run on any MEDLINE file in a batch mode. As an example, the top 3 medical specialties for the set of 60 articles published in BioMed Central Medical Informatics & Decision Making, which are currently indexed in MEDLINE are: information science, organization and administration and medical informatics.

Conclusion

We have presented a MEDLINE categorization algorithm in order to classify the medical specialties addressed in any MEDLINE file in the form of a ranked list of relevant specialties. The categorization method introduced in this paper is based on the manual indexing of resources with MeSH (terms/subheadings) pairs by NLM indexers. This algorithm may be used as a new bibliometric tool.
Direct interaction between the catalytic subunit of Protein Phosphatase 1 and pRb
Authors: Vietri Michele , Bianchi Mariarita , Ludlow John W , Mittnacht Sibylle , Villa-Moruzzi Emma
Published: February 2006

Background

The product of the retinoblastoma-susceptibility gene (pRb) is a substrate for Protein Phosphatase 1 (PP1). At mitotic exit, all three PP1 isoforms, α, γ1 and δ, bind to pRb and dephosphorylate its Ser/Thr sites in a sequential and site-specific way. The pRb-C terminal has been reported to be necessary and sufficient for PP1α binding. The present study investigated whether the three PP1 isoforms from mitotic or asynchronous HeLa cells associate differentially with wild-type and pRb mutants, as well as the holoenzyme composition of the pRb-directed PP1.

Results

The requirement for the entire pRb molecule to achieve optimal PP1-binding was indicated by the fact that full-length pRb displayed the highest affinity for all three PP1 isoforms. Ser/Thr-to-Ala substitution for up to 14 pRb sites did not affect the ability of pRb to bind the PP1 isoforms derived from mitotic or asynchronous HeLa cells, thus suggesting that the phosphate-accepting residues on pRb do not regulate the interaction with PP1. To probe for the presence of PP1 targeting subunits in the pRb-directed PP1 complex, PP1 from mitotic or asynchronous HeLa cells was isolated by affinity chromatography on GST-Rb (either full-length or its deletion mutants Rb-big pocket or Rb-C-terminal). The PP1 was always obtained as free catalytic subunit, displaying all three isoforms, thus suggesting direct interaction between pRb and PP1. The direct association was confirmed by the ability of pRb to pull-down purified PP1 catalytic subunits and by in vitro reconstitution of a complex between PP1 catalytic subunit and the pRb-C-terminal.

Conclusion

The work indicated that the full length of the pRb molecule is required for optimal interaction with the PP1 isoforms and that the association between pRb and PP1 isoforms is direct.
Laboratory-based surveillance of current antimicrobial resistance patterns and trends among Staphylococcus aureus: 2005 status in the United States
Authors: Styers David , Sheehan Daniel J , Hogan Patricia , Sahm Daniel F
Published: February 2006

Background

The virulence, antimicrobial resistance, and prevalence of S. aureus underscores the need for up-to-date and extensive insights regarding antimicrobial susceptibility trends. One approach to meet this need is analysis of clinical laboratory – based surveillance data.

Methods

Data from The Surveillance Network-USA (TSN), an electronic surveillance network that collects microbiology data from 300 clinical microbiology laboratories across the United States, were used as the source for analysis that included prevalence of S. aureus in clinical specimens, MRSA and multi-drug resistance phenotype rates and trends according to patient location, geographic distributions, and specimen source.

Results

S. aureus was the most prevalent species isolated from inpatient specimens (18.7% of all bacterial isolates) and the second most prevalent (14.7%) from outpatient specimens. In March 2005 MRSA rates were 59.2%, 55%, and 47.9% for strains from non-ICU inpatients, ICU, and outpatients, respectively. This trend was noted in all nine US Bureau of Census regions and multi-drug resistance phenotypes (resistance to ≥ 3 non-beta-lactams) was common among both inpatient MRSA (59.9%) and outpatient MRSA (40.8%). Greater than 90% of multi-drug resistant MRSA were susceptible to trimethoprim-sulfamethoxazole, linezolid, and vancomycin.

Conclusion

Prevalence of MRSA among both inpatient and outpatient specimens continues to increase with multi-drug resistance as a common phenotype. Continued emergence of outpatient MRSA that exhibit multi-drug resistant phenotypes has important implications for developing and evolving outpatient treatment guidelines.
The match between motivation and performance management of health sector workers in Mali
Authors: Dieleman Marjolein , Toonen Jurrien , Touré Hamadassalia , Martineau Tim
Published: February 2006

Human resources for health (HRH) play a central role in improving accessibility to services and quality of care. Their motivation influences this. In Mali, operational research was conducted to identify the match between motivation and the range and use of performance management activities.

Objectives

To describe the factors motivating and demotivating health workers in Mali and match the motivators with the implementation of performance management.

Methods

First an exploratory qualitative study was conducted: 28 interviews and eight group discussions were held. This was followed by a cross-sectional survey, during which 370 health workers were interviewed. The study population consisted of health workers of eight professional groups. The following issues were investigated:

• motivating and demotivating factors;

• experiences with performance management, including: job descriptions, continuous education, supervision, performance appraisal and career development.

Findings

The study showed that the main motivators of health workers were related to responsibility, training and recognition, next to salary. These can be influenced by performance management (job descriptions, supervisions, continuous education and performance appraisal). Performance management is not optimally implemented in Mali, as job descriptions were not present or were inappropriate; only 13% of interviewees received 4× per year supervision, and training needs were not analysed. Some 48% of the interviewees knew their performance had been appraised in the last two years; the appraisals were perceived as subjective. No other methods were in place to show recognition. The results enabled the research team to propose adaptations or improvements upon existing performance management.

Conclusion

The results showed the importance of adapting or improving upon performance management strategies to influence staff motivation. This can be done by matching performance management activities to motivators identified by operational research.
An inquiry into good hospital governance: A New Zealand-Czech comparison
Authors: Ditzel Elizabeth , Štrach Pavel , Pirozek Petr
Published: February 2006

Background

This paper contributes to research in health systems literature by examining the role of health boards in hospital governance. Health care ranks among the largest public sectors in OECD countries. Efficient governance of hospitals requires the responsible and effective use of funds, professional management and competent governing structures. In this study hospital governance practice in two health care systems – Czech Republic and New Zealand – is compared and contrasted. These countries were chosen as both, even though they are geographically distant, have a universal right to 'free' health care provided by the state and each has experienced periods of political change and ensuing economic restructuring. Ongoing change has provided the impetus for policy reform in their public hospital governance systems.

Methods

Two comparative case studies are presented. They define key similarities and differences between the two countries' health care systems. Each public hospital governance system is critically analysed and discussed in light of D W Taylor's nine principles of 'good governance'.

Results

While some similarities were found to exist, the key difference between the two countries is that while many forms of 'ad hoc' hospital governance exist in Czech hospitals, public hospitals in New Zealand are governed in a 'collegiate' way by elected District Health Boards. These findings are discussed in relation to each of the suggested nine principles utilized by Taylor.

Conclusion

This comparative case analysis demonstrates that although the New Zealand and Czech Republic health systems appear to show a large degree of convergence, their approaches to public hospital governance differ on several counts. Some of the principles of 'good governance' existed in the Czech hospitals and many were practiced in New Zealand. It would appear that the governance styles have evolved from particular historical circumstances to meet each country's specific requirements. Whether or not current practice could be improved by paying closer attention to theoretical models of 'good governance' is debatable.