bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical Studies in Action Selection with Reinforcement Learning
Authors: Whiteson Shimon , Taylor Matthew E. , Stone Peter 
Published: February 2007

To excel in challenging tasks, intelligent agents need sophisticated mechanisms for action selection: they need policies that dictate what action to take in each situation. Reinforcement learning (RL) algorithms are designed to learn such policies given only positive and negative rewards. Two contrasting approaches to RL that are currently in popular use are temporal difference (TD) methods, which learn value functions, and evolutionary methods, which optimize populations of candidate policies. Both approaches have had practical successes but few studies have directly compared them. Hence, there are no general guidelines describing their relative strengths and weaknesses. In addition, there has been little cross-collaboration, with few attempts to make them work together or to apply ideas from one to the other. In this article we aim to address these shortcomings via three empirical studies that compare these methods and investigate new ways of making them work together. First, we compare the two approaches in a benchmark task and identify variations of the task that isolate factors critical to the performance of each method. Second, we investigate ways to make evolutionary algorithms excel at on-line tasks by borrowing exploratory mechanisms traditionally used by TD methods. We present empirical results demonstrating a dramatic performance improvement. Third, we explore a novel way of making evolutionary and TD methods work together by using evolution to automatically discover good representations for TD function approximators. We present results demonstrating that this novel approach can outperform both TD and evolutionary methods alone.
Where is the pilot? The changing shapes of governance in the European hospital sector
Authors: Eeckloo Kristof , Delesie Luc , Vleugels Arthur 
Published: February 2007

Hospital governance refers to the complex of checks and balances that determine how decisions are made within the top structures of hospitals. This article explores the essentials of the concept by analysing the root notion of governance and comparing it with applications in other sectors. Recent developments that put pressure on the decision-making system within hospitals are outlined. Examples from the UK, France and the Netherlands are presented. Based on an evaluation of the current state of affairs, a research framework is developed, focusing on the determinants of governance configurations within the national healthcare systems and the wider legal and socio-economic context, as well as on the impact of governance configurations on the efficiency of the governing bodies and overall hospital performance. The article concludes with a preview of the European Hospital Governance Project, which follows the outlines of the described research framework. New techniques of data mining that are used in this project are explained by means of a real data example.
Non-surgical management of stress urinary incontinence: ambulatory treatments for leakage associated with stress (ATLAS) trial
Authors: Richter Holly E , Burgio Kathryn L , Goode Patricia S , Borello-France Diane , Bradley Catherine S , Brubaker Linda , Handa Victoria L , Fine Paul M , Visco Anthony G , Zyczynski Halina M , Wei John T , Weber Anne M ,   for the Pelvic Floor Disorders Network
Published: February 2007

Background Non-surgical treatment for stress urinary incontinence (SUI) is recommended as first-line therapy, yet few prospective studies and no randomized trials compare the most common non-surgical treatments for SUI. Purpose To present the design and methodology of the ambulatory treatments for leakage associated with stress (ATLAS) trial, a randomized clinical trial comparing three interventions for predominant SUI in women: intravaginal continence pessary; behavioral therapy (including pelvic floor muscle training and exercise and bladder control strategies); and a combination of the two treatments. Methods Treatment outcome measures, collected at 12 weeks and six and 12 months post randomization, include the Patient Global Impression of Improvement (PGI-I), the Stress Incontinence Scale of the Pelvic Floor Distress Inventory (PFDI), seven-day bladder diaries, Pelvic Floor Impact Questionnaire (PFIQ), Pelvic Organ Prolapse-Urinary Incontinence Sexual Function Questionnaire (PISQ-12), Patient Satisfaction Questionnaire (PSQ) and the Medical Outcomes Study Short Form Health Survey (SF-36). Limitations The study design reduces most common biases, but some degree of selection bias may remain. Conclusion This trial will provide useful information to help counsel women with stress and mixed incontinence about the relative efficacy and satisfaction with pessary, behavioral therapy and both treatments combined.
The impact of helminths on the response to immunization and on the incidence of infection and disease in childhood in Uganda: design of a randomized, double-blind, placebo-controlled, factorial trial of deworming interventions delivered in pregnancy and early childhood [ISRCTN32849447]
Authors: Elliott Alison M , Kizza Moses , Quigley Maria A , Ndibazza Juliet , Nampijja Margaret , Muhangi Lawrence , Morison Linda , Namujju Proscovia B , Muwanga Moses , Kabatereine Narcis , Whitwortha James AG 
Published: February 2007

Background Helminths have profound effects on the immune response, allowing long-term survival of parasites with minimal damage to the host. Some of these effects “spill-over”, altering responses to non-helminth antigens or allergens. It is suggested that this may lead to impaired responses to immunizations and infections, while conferring benefits against inflammatory responses in allergic and autoimmune disease. These effects might develop in utero, through exposure to maternal helminth infections, or through direct exposure in later life. Purpose To determine the effects of helminths and their treatment in pregnancy and in young children on immunological and disease outcomes in childhood. Methods The trial has three randomized, double-blind, placebo-controlled interventions at two times, in two people: a pregnant woman and her child. Pregnant women are randomized to albendazole or placebo and praziquantel or placebo. At age 15 months their children are randomized to three-monthly albendazole or placebo, to continue to age five years. The proposed designation for this sequence of interventions is a 2 × 2(×2) factorial design. Children are immunized with BCG and against polio, Diphtheria, tetanus, Pertussis, Haemophilus, hepatitis B and measles. Primary immunological outcomes are responses to BCG antigens and tetanus toxoid in whole blood cytokine assays and antibody assays at one, three and five years of age. Primary disease outcomes are incidence of malaria, pneumonia, diarrhoea, tuberculosis, measles, vertical HIV transmission, and atopic disease episodes, measured at clinic visits and twice-monthly home visits. Effects on anaemia, growth and intellectual development are also assessed. Conclusion This trial, with a novel design comprising related interventions in pregnant women and their offspring, is the first to examine effects of helminths and their treatment in pregnancy and early childhood on immunological, infectious disease and allergic disease outcomes. The results will enhance understanding of both detrimental and beneficial effects of helminth infection and inform policy.
Sample-size calculations for trials that inform individual treatment decisions: a ‘true-choice’ approach
Authors: Girling Alan J , Lilford Richard J , Braunholtz David A , Gillett Wayne R 
Published: February 2007

Background Sample size decisions for clinical trials should be taken in such a way as to maximize informed choice by reducing scientific uncertainty about the consequences of an intervention. Purpose Recent approaches to trial design have focused on the potential decision impact of the trial when deciding whether the trial should be undertaken, and how large it ought to be. For the most part these approaches are concerned with the impact of trials either on clinical opinion or on collective reimbursement recommendations. Our purpose is to model the contribution of clinical trials to patient-level decision-making and to propose a way of assessing this contribution at the design stage. Methods The model is developed within the framework of Bayesian decision theory. It is presumed that some patients make choices that they would not have made in the presence of perfect information about the likely consequences. These ‘false’ choices would be reversed in response to a fully informative (ie, very large) trial of the competing interventions. By contrast, choices that would not change in response to a fully informative trial are termed ‘true’ choices since they accurately reflect patient preferences. Results An impact plot is proposed which maps how the expected numbers of ‘true’ and ‘false’ choices change in response to a trial of any given size. The approach is illustrated with reference to the choice of delivery mode for term breech presentation, using data obtained before the recent term breech trial. Applications in other contexts are indicated. Limitations No account is taken of the magnitude of expressed patient preferences for one treatment over another. The upside is that the need for detailed utility-elicitation is obviated. Conclusions The approach is a pragmatic aid to trial design in settings where patient preference drives the choice between alternative treatments.
A Practical Church Unity within Secular Hospitals
Authors: Balboni Michael 
Published: February 2007

AbstractEcclesial unity among Christian physicians is jeopardized by the culture of secular medicine. The medical context, rather than being a neutral sphere, has increasingly become a context that cuts loose and reshapes church members into a secular ecclesia. This thesis is demonstrated through focus groups composed of Christian physician-residents within Harvard Medical School residency programs. The interviews describe how many Christian physicians are psychologically isolated and spiritually endangered because of compliance to secular expectations within academic teaching hospitals. In contrast, the key to undoing secular atomization stems from the nature of the church as a people gathered in the presence of Christ. Thus, the essay develops an ecclesiology that focuses on the manifestation of unity in its local relationships and embodied practices. Despite severe time constraints, Christian physicians have the opportunity to reconstitute a unified church within the secular by pursuing one another in love and offering tangible signs of solidarity.
A complex splicing defect associated with homozygous ankyrin-deficient hereditary spherocytosis
Authors: Edelman E. Jennifer , Maksimova Yelena , Duru Feride , Altay Cigdem , Gallagher Patrick G. 
Published: February 2007

Abstract
Defects in erythrocyte ankyrin are the most common cause of typical, dominant hereditary spherocytosis (HS). Detection of ankyrin gene mutations has been complicated by allelic heterogeneity, large gene size, frequent de novo mutations, and associated mRNA instability. Using denaturing high-performance liquid chromatography (DHPLC)–based mutation detection, a mutation in the splice acceptor of exon 17 was discovered in a Turkish family. Reticulocyte RNA and functional minigene splicing assays in heterologous cells revealed that this mutation was associated with a complex pattern of aberrant splicing, suggesting that removal of intron 16 is important for ordered ankyrin mRNA splicing. As predicted by clinical, laboratory, and biochemical studies, the parents were heterozygous and the proband was homozygous for this mutation. These data indicate that DHPLC offers a highly sensitive, economic, and rapid method for mutation detection and, unlike previously suggested, homozygosity for a mutation associated with dominant ankyrin-linked HS may be compatible with life.
Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
Authors: Venneri Mary Anna , Palma Michele De , Ponzoni Maurilio , Pucci Ferdinando , Scielzo Cristina , Zonari Erika , Mazzieri Roberta , Doglioni Claudio , Naldini Luigi 
Published: February 2007

Abstract
Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), have been implicated in tumor progression. We recently described a lineage of mouse monocytes characterized by expression of the Tie2 angiopoietin receptor and required for the vascularization and growth of several tumor models. Here, we report that TIE2 expression in human blood identifies a subset of monocytes distinct from classical inflammatory monocytes and comprised within the less abundant “resident” population. These TIE2-expressing monocytes (TEMs) accounted for 2% to 7% of blood mononuclear cells in healthy donors and were distinct from rare circulating endothelial cells and progenitors. In human cancer patients, TEMs were observed in the blood and, intriguingly, within the tumors, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in nonneoplastic tissues. In vitro, TEMs migrated toward angiopoietin-2, a TIE2 ligand released by activated endothelial cells and angiogenic vessels, suggesting a homing mechanism for TEMs to tumors. Purified human TEMs, but not TEM-depleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumors, suggesting a potentially critical role of TEMs in human cancer progression. Human TEMs may provide a novel, biologically relevant marker of angiogenesis and represent a previously unrecognized target of cancer therapy.
Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia
Authors: Fulci Valerio , Chiaretti Sabina , Goldoni Marina , Azzalin Gianluca , Carucci Nicoletta , Tavolaro Simona , Castellano Leandro , Magrelli Armando , Citarella Franca , Messina Monica , Maggio Roberta , Peragine Nadia , Santangelo Simona , Mauro Francesca Romana , Landgraf Pablo , Tuschl Thomas , Weir David B. , Chien Minchen , Russo James J. , Ju Jingyue , Sheridan Robert , Sander Chris , Zavolan Mihaela , Guarini Anna , Foà Robin , Macino Giuseppe 
Published: February 2007

Abstract
MicroRNAs (miRNAs) are a novel class of small noncoding RNAs that modulate the expression of genes at the posttranscriptional level. These small molecules have been shown to be involved in cancer, apoptosis, and cell metabolism. In the present study we provide an informative profile of the expression of miRNAs in primary chronic lymphocytic leukemia (CLL) cells using 2 independent and quantitative methods: miRNA cloning and quantitative real-time–polymerase chain reaction (qRT-PCR) of mature miRNAs. Both approaches show that miR-21 and miR-155 are dramatically overexpressed in patients with CLL, although the corresponding genomic loci are not amplified. miR-150 and miR-92 are also significantly deregulated in patients with CLL. In addition, we detected a marked miR-15a and miR-16 decrease in about 11% of cases. Finally, we identified a set of miRNAs whose expression correlates with biologic parameters of prognostic relevance, particularly with the mutational status of the IgVH genes. In summary, the results of this study offer for the first time a comprehensive and quantitative profile of miRNA expression in CLL and their healthy counterpart, suggesting that miRNAs could play a primary role in the disease itself.
AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides
Authors: Conchillo-Solé Oscar , de Groot Natalia S , Avilés Francesc X , Vendrell Josep , Daura Xavier , Ventura Salvador 
Published: February 2007

Abstract

Background
Protein aggregation correlates with the development of several debilitating human disorders of growing incidence, such as Alzheimer's and Parkinson's diseases. On the biotechnological side, protein production is often hampered by the accumulation of recombinant proteins into aggregates. Thus, the development of methods to anticipate the aggregation properties of polypeptides is receiving increasing attention. AGGRESCAN is a web-based software for the prediction of aggregation-prone segments in protein sequences, the analysis of the effect of mutations on protein aggregation propensities and the comparison of the aggregation properties of different proteins or protein sets.

Results
AGGRESCAN is based on an aggregation-propensity scale for natural amino acids derived from in vivo experiments and on the assumption that short and specific sequence stretches modulate protein aggregation. The algorithm is shown to identify a series of protein fragments involved in the aggregation of disease-related proteins and to predict the effect of genetic mutations on their deposition propensities. It also provides new insights into the differential aggregation properties displayed by globular proteins, natively unfolded polypeptides, amyloidogenic proteins and proteins found in bacterial inclusion bodies.

Conclusion
By identifying aggregation-prone segments in proteins, AGGRESCAN http://bioinf.uab.es/aggrescan/ shall facilitate (i) the identification of possible therapeutic targets for anti-depositional strategies in conformational diseases and (ii) the anticipation of aggregation phenomena during storage or recombinant production of bioactive polypeptides or polypeptide sets.
Tissue and subcellular distribution of CLIC1
Authors: Ulmasov Barbara , Bruno Jonathan , Woost Philip G , Edwards John C 
Published: February 2007

Abstract

Background
CLIC1 is a chloride channel whose cellular role remains uncertain. The distribution of CLIC1 in normal tissues is largely unknown and conflicting data have been reported regarding the cellular membrane fraction in which CLIC1 resides.

Results
New antisera to CLIC1 were generated and were found to be sensitive and specific for detecting this protein. These antisera were used to investigate the distribution of CLIC1 in mouse tissue sections and three cultured cell lines. We find CLIC1 is expressed in the apical domains of several simple columnar epithelia including glandular stomach, small intestine, colon, bile ducts, pancreatic ducts, airway, and the tail of the epididymis, in addition to the previously reported renal proximal tubule. CLIC1 is expressed in a non-polarized distribution in the basal epithelial cell layer of the stratified squamous epithelium of the upper gastrointesitinal tract and the basal cells of the epididymis, and is present diffusely in skeletal muscle. Distribution of CLIC1 was examined in Panc1 cells, a relatively undifferentiated, non-polarized human cell line derived from pancreatic cancer, and T84 cells, a human colon cancer cell line which can form a polarized epithelium that is capable of regulated chloride transport. Digitonin extraction was used to distinguish membrane-inserted CLIC1 from the soluble cytoplasmic form of the protein. We find that digitonin-resistant CLIC1 is primarily present in the plasma membrane of Panc1 cells. In T84 cells, we find digitonin-resistant CLIC1 is present in an intracellular compartment which is concentrated immediately below the apical plasma membrane and the extent of apical polarization is enhanced with forskolin, which activates transepithelial chloride transport and apical membrane traffic in these cells. The sub-apical CLIC1 compartment was further characterized in a well-differentiated mouse renal proximal tubule cell line. The distribution of CLIC1 was found to overlap that of megalin and the sodium-phosphate cotransporter, NaPi-II, which are markers of the apical endocytic/recycling compartment in proximal tubule.

Conclusion
The cell and tissue specific patterns of CLIC1 expression suggest it may play distinct roles in different cell types. In certain polarized columnar epithelia, it may play a role in apical membrane recycling.
Temporal dynamics of gene expression in the lung in a baboon model of E. coli sepsis
Authors: Zhu Hua , Tang Yuhong , Ivanciu Lacramioara , Centola Michael , Lupu Cristina , Taylor Fletcher B , Lupu Florea 
Published: February 2007

Abstract

Background
Bacterial invasion during sepsis induces disregulated systemic responses that could lead to fatal lung failure. The purpose of this study was to relate the temporal dynamics of gene expression to the pathophysiological changes in the lung during the first and second stages of E. coli sepsis in baboons.

Results
Using human oligonucleotide microarrays, we have explored the temporal changes of gene expression in the lung of baboons challenged with sublethal doses of E. coli. Temporal expression pattern and biological significance of the differentially expressed genes were explored using clustering and pathway analysis software. Expression of selected genes was validated by real-time PCR. Cytokine levels in tissue and plasma were assayed by multiplex ELISA. Changes in lung ultrastructure were visualized by electron microscopy. We found that genes involved in primary inflammation, innate immune response, and apoptosis peaked at 2 hrs. Inflammatory and immune response genes that function in the stimulation of monocytes, natural killer and T-cells, and in the modulation of cell adhesion peaked at 8 hrs, while genes involved in wound healing and functional recovery were upregulated at 24 hrs.

Conclusion
The analysis of gene expression modulation in response to sepsis provides the baseline information that is crucial for the understanding of the pathophysiology of systemic inflammation and may facilitate the development of future approaches for sepsis therapy.
Effective quantitative real-time polymerase chain reaction analysis of the parkin gene (PARK2) exon 1–12 dosage
Authors: Shadrina Maria I , Semenova Elena V , Slominsky Petr A , Bagyeva Gulbahar H , Illarioshkin Sergei N , Ivanova-Smolenskaia Irina I , Limborska Svetlana A 
Published: February 2007

Abstract

Background
One of the causes of Parkinson's disease is mutations in the PARK2 gene. Deletions and duplications of single exons or exon groups account for a large proportion of the gene mutations. Direct detection of these mutations can be used for the diagnosis of Parkinson's disease.

Methods
To detect these mutations, we developed an effective technique based on the real-time TaqMan PCR system, which allows us to evaluate the copynumbers of the PARK2 gene exons by comparing the intensity of the amplification signals from some exon of this gene with that of the β-globin gene (the internal control).

Results
We analyzed rearrangements in exons 1–12 of the PARK2 gene in 64 patients from Russia with early-onset Parkinson's disease. The frequency of these mutations in our patients was 14%.

Conclusion
We have developed a simple, accurate, and reproducible method applicable to the rapid detection of exon rearrangements in the PARK2 gene. It is suitable for the analysis of large patient groups, and it may become the basis for a diagnostic test.