bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of refractory chronic cluster headache by chronic occipital nerve stimulation
Authors: Fontaine Denys , Christophe Sol Jean , Raoul Sylvie , Fabre Nelly , Geraud Gilles , Magne Christine , Sakarovitch Charlotte , Lanteri-Minet Michel 
Published: July 2011

Background: Greater occipital nerve stimulation (ONS) has been recently proposed to treat severe chronic cluster headache patients (CCH) refractory to medical treatment. We report the results of a French multidisciplinary cohort study. Methods: Thirteen CCH patients were operated and data were collected prospectively. All of them suffered from CCH according to the International Headache Society classification, lasting for more than 2 years, refractory to pharmacological prophylactic treatment with adequate trials, with at least one daily attack. Chronic ONS was delivered through a subcutaneous occipital electrode connected to an implanted generator, in order to induce paraesthesias perceived locally in the lower occipital region. Results: After surgery (mean follow-up 14,6 months), the mean attack frequency and intensity decreased by 68% and 49%, respectively. At last follow-up, 10/13 patients were considered as responders (improvement >50%). Prophylactic treatment could be stopped or reduced in 8/13 cases. Local infection occurred in one patient, leading to hardware removal. Conclusions: Our data confirmed the results of the 36 similar cases reported in the literature, suggesting that ONS may act as a prophylactic treatment in chronic CH. Considering their respective risks, ONS should be proposed before deep brain stimulation in severe refractory CCH patients.
The Clinical Utility and Diagnostic Performance of Magnetic Resonance Imaging for Identification of Early and Advanced Knee Osteoarthritis
Authors: Quatman Carmen E. , Hettrich Carolyn M. , Schmitt Laura C. , Spindler Kurt P. 
Published: July 2011

Background: Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of noninvasive interventions. Purpose: To systematically review the literature relative to the following questions: (1) Is magnetic resonance imaging (MRI) a valid, sensitive, specific, accurate, and reliable instrument to identify knee articular cartilage abnormalities compared with arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design: Systematic review. Methods: A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), SCOPUS (from 1996), and EMBASE (from 1974) databases. Results: Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared with arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26% and 96%. Specificity and accuracy were reported between 50% and 100% and between 49% and 94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0% and 86%, 48% and 95%, and 5% and 94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed, and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusion: There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Because of heterogeneity of MRI sequences, it is not possible to make definitive conclusions regarding its global clinical utility for guiding diagnosis and treatment strategies. Clinical Relevance: Traumatic sports injuries to the knee may be significant precursor events to early onset of posttraumatic osteoarthritis. Magnetic resonance imaging may aid in early identification of structural injuries to articular cartilage as evidenced by articular cartilage degeneration grading.
Real-time modelling of transient operation of turbocharged diesel engines
Authors: Gambarotta A , Lucchetti G , Vaja I 
Published: July 2011

In fact, nowadays the optimization of engines and powertrains towards cleaner, more fuel-efficient, and safer vehicles requires virtual tools for the simulation of the whole system well in advance of the design process. Moreover, management and diagnostic issues have key roles in the exploitation of the used technologies and solutions (e.g. double-stage turbocharging, and high- and low-pressure exhaust gas recirculation). Without forgetting the importance of experimental investigations, mathematical models are very useful tools to improve both the performance and the behaviour of engines and powertrains, with applications ranging from optimization of the system layout to definition and testing of control strategies. Starting from a brief overview of actual mathematical tools for simulation of the transient operation of diesel engines, several considerations are reported on the modelling criteria and approaches with reference to fast zero-dimensional mean-value models of engines and powertrains. An original library that the present authors and co-workers have built up in recent years for the ‘real-time’ simulation of diesel engines is described, and several applications are reported. The presented models were validated and used to simulate the transient behaviour of typical automotive diesel engines.
Redesigning a large school-based clinical trial in response to changes in community practice
Authors: Gerald Lynn B , Gerald Joe K , McClure Leslie A , Harrington Kathy , Erwin Sue , Bailey William C 
Published: July 2011

Background Asthma exacerbations are seasonal with the greatest risk in elementary-age students occurring shortly after returning to school following summer break. Recent research suggests that this seasonality in children is primarily related to viral respiratory tract infections. Regular hand washing is the most effective method to prevent the spread of viral respiratory infections; unfortunately, achieving hand washing recommendations in schools is difficult. Therefore, we designed a study to evaluate the effect of hand sanitizer use in elementary schools on exacerbations among children with asthma. Purpose To describe the process of redesigning the trial in response to changes in the safety profile of the hand sanitizer as well as changes in hand hygiene practice in the schools. Methods The original trial was a randomized, longitudinal, subject-blinded, placebo-controlled, community-based crossover trial. The primary aim was to evaluate the incremental effectiveness of hand sanitizer use in addition to usual hand hygiene practices to decrease asthma exacerbations in elementary-age children. Three events occurred that required major modifications to the original study protocol: (1) safety concerns arose regarding the hand sanitizer’s active ingredient; (2) no substitute placebo hand sanitizer was available; and (3) community preferences changed regarding hand hygiene practices in the schools. Results The revised protocol is a randomized, longitudinal, community-based crossover trial. The primary aim is to evaluate the incremental effectiveness of a two-step hand hygiene process (hand hygiene education plus institutionally provided alcohol-based hand sanitizer) versus usual care to decrease asthma exacerbations. Enrollment was completed in May 2009 with 527 students from 30 schools. The intervention began in August 2009 and will continue through May 2011. Study results should be available at the end of 2011. Limitations The changed design does not allow us to directly measure the effectiveness of hand sanitizer use as a supplement to traditional hand washing practices. Conclusions The need to balance a rigorous study design with one that is acceptable to the community requires investigators to be actively involved with community collaborators and able to adapt study protocols to fit changing community practices.
Providing the results of research to participants: a mixed-method study of the benefits and challenges of a consultative approach
Authors: Dixon-Woods Mary , Tarrant Carolyn , Jackson Clare J , Jones David R , Kenyon Sara 
Published: July 2011

Background How best to provide the findings of research to study participants remains poorly understood. Purpose We aimed to develop, deliver, and evaluate a consultative approach to inform provision of feedback about research findings to participants in the Oracle Children Study (OCS). The OCS had identified adverse outcomes for some children whose mothers had been prescribed antibiotics as part of a trial in pregnancy. Methods An iterative process, including focus groups with OCS participants and consultation with other OCS stakeholders, was used to inform the development of a feedback package, including a results leaflet, for OCS participants. A questionnaire survey of participants’ reactions to receiving the results leaflet was conducted. The Kolmogorov–Smirnov two-sample test was used to compare responses between different groups of respondents. Analysis of open-ended comments on the questionnaire was based on the constant comparative method. Results Three focus groups with study participants provided insight into the potential emotional impact of receiving the results and into how the results might most clearly be explained. Negotiations with other stakeholders identified other priorities, including the need for scientific credibility. These multiple needs had to be balanced. The results leaflet was posted to all 4676 UK OCS participants. Survey responses were received from 1124 (25%) of participants. They indicated that the feedback was mostly well received by participants. Those whose children were affected by conditions associated with increased risk from trial participation were more likely to experience emotional distress on receiving the trial results, but there was also evidence of some other unanticipated impacts. Limitations This study is limited by the low response rate to the survey. Conclusions Important lessons can be learned from using a consultative approach to developing feedback about research results for study participants. Especially where the findings are unwelcome, feedback development may involve methodological, ethical, emotional, and practical challenges, be resource-intensive, and need early planning.
Beyond the 3+3 method: expanded algorithms for dose- escalation in Phase I oncology trials of two agents
Authors: Braun Thomas M , Alonzo Todd A 
Published: July 2011

Background The number of published Phase I trials for determining a maximum tolerated combination of two agents is increasing, with a majority of those trials suffering from poor study design. A recent editorial proposed a 3+3+3 design, which takes the traditional 3+3 design used for one-agent dose-finding and adds an additional possible cohort of three patients. Purpose To investigate the utility and performance of the 3+3+3, and more generally, A+B+C algorithmic designs, in Phase I trials of two-agent combinations and to discuss the issues related to such designs. Methods Operating characteristics for an A+B+C design can be computed exactly in the statistical software package R using publicly available functions created by the authors. Using those functions, six different A+B+C designs are compared in six different settings with respect to the dose-limiting toxicity rate of combinations that each design selects as the maximum tolerated combination, as well as the average total number of patients required by each design and the average number of patients assigned to each combination. Results Allowing for simultaneous escalation of doses of both agents does not increase patients' exposure to overly toxic combinations, yet increases the probability of identifying the maximum tolerated combination when it occurs at higher doses of either agent, than a design that forbids simultaneous escalation. Designs in which A ≤ 3 tend to target combinations with dose-limiting toxicity rates higher than designs in which A ≥ 4. Limitations The implicitly targeted dose-limiting toxicity rate of any given algorithmic design is not transparent, requiring computation of results under a variety of settings to help understand the operating characteristics of that design. Thus, the appropriate A+B+C design will vary from trial to trial. A+B+C designs also have ‘short memory’, as escalation decisions are based primarily on the most recent cohort of patients. Conclusions Algorithmic A+B+C designs are potentially useful in the design of Phase I trials of combinations of two agents. However, a head-to-head comparison to model-based designs is needed to warrant their general use.
The 6-MP versus placebo clinical trial in acute leukemia
Authors: Gehan Edmund A , Freireich Emil J 
Published: July 2011

Background This article gives the status of clinical cancer research in the 1950's–1960's and tells the story of the development and conduct of the 6-mercaptopurine (6-MP) versus placebo clinical trial in acute leukemia through the initiation, design, conduct and analysis stages, with emphasis on the ethical aspects of randomizing patients to 6-MP or placebo when in remission. Purpose The specific objective was to compare the lengths of remission for patients receiving 6-MP or placebo after achieving complete or partial remission from steroid treatment. Methods A randomized, double-blind, placebo controlled sequential study was conducted in which patients were paired by remission status at each of the eleven institutions participating in the study, and randomized to 6-MP or placebo within each pair of patients. A preference for 6-MP or placebo was recorded depending on which patient in the pair had the longer remission. The preferences were plotted according to a restricted sequential procedure devised by Peter Armitage and, depending on which boundary of the design was crossed, a statistically significant difference could be declared favoring 6-MP, placebo or no preference. Conclusions The trial established the efficacy of 6-MP for maintaining longer remissions in acute leukemia and led to the concept of 'adjuvant chemotherapy', namely that patients with minimal disease have a substantially better response to chemotherapy than patients with advanced disease, a concept that has been followed in many other forms of cancer. Statistically, the fact that many patients were still in remission when the study was stopped (i.e. the length of remission data for these patients was 'right censored') led to the development of a generalized Wilcoxon test and was an important influence on Cox's development of the proportional hazards model. The trial had an innovative design in the early 1960's and has been an important influence on subsequent clinical research in cancer and statistical research in survival analysis.
Macrophage development from HSCs requires PU.1-coordinated microRNA expression
Authors: Ghani Saeed , Riemke Pia , Schönheit Jörg , Lenze Dido , Stumm Jürgen , Hoogenkamp Maarten , Lagendijk Anne , Heinz Sven , Bonifer Constanze , Bakkers Jeroen , Abdelilah-Seyfried Salim , Hummel Michael , Rosenbauer Frank 
Published: July 2011

AbstractThe differentiation of HSCs into myeloid lineages requires the transcription factor PU.1. Whereas PU.1-dependent induction of myeloid-specific target genes has been intensively studied, negative regulation of stem cell or alternate lineage programs remains incompletely characterized. To test for such negative regulatory events, we searched for PU.1-controlled microRNAs (miRs) by expression profiling using a PU.1-inducible myeloid progenitor cell line model. We provide evidence that PU.1 directly controls expression of at least 4 of these miRs (miR-146a, miR-342, miR-338, and miR-155) through temporally dynamic occupation of binding sites within regulatory chromatin regions adjacent to their genomic coding loci. Ectopic expression of the most robustly induced PU.1 target miR, miR-146a, directed the selective differentiation of HSCs into functional peritoneal macrophages in mouse transplantation assays. In agreement with this observation, disruption of Dicer expression or specific antagonization of miR-146a function inhibited the formation of macrophages during early zebrafish (Danio rerio) development. In the present study, we describe a PU.1-orchestrated miR program that mediates key functions of PU.1 during myeloid differentiation.
Genome-wide SNP discovery in tetraploid alfalfa using 454 sequencing and high resolution melting analysis
Authors: Han Yuanhong , Kang Yun , Torres-Jerez Ivone , Cheung Foo , Town Christopher D , Zhao Patrick X , Udvardi Michael K , Monteros Maria J 
Published: July 2011

Abstract

Background
Single nucleotide polymorphisms (SNPs) are the most common type of sequence variation among plants and are often functionally important. We describe the use of 454 technology and high resolution melting analysis (HRM) for high throughput SNP discovery in tetraploid alfalfa (Medicago sativa L.), a species with high economic value but limited genomic resources.

Results
The alfalfa genotypes selected from M. sativa subsp. sativa var. 'Chilean' and M. sativa subsp. falcata var. 'Wisfal', which differ in water stress sensitivity, were used to prepare cDNA from tissue of clonally-propagated plants grown under either well-watered or water-stressed conditions, and then pooled for 454 sequencing. Based on 125.2 Mb of raw sequence, a total of 54,216 unique sequences were obtained including 24,144 tentative consensus (TCs) sequences and 30,072 singletons, ranging from 100 bp to 6,662 bp in length, with an average length of 541 bp. We identified 40,661 candidate SNPs distributed throughout the genome. A sample of candidate SNPs were evaluated and validated using high resolution melting (HRM) analysis. A total of 3,491 TCs harboring 20,270 candidate SNPs were located on the M. truncatula (MT 3.5.1) chromosomes. Gene Ontology assignments indicate that sequences obtained cover a broad range of GO categories.

Conclusions
We describe an efficient method to identify thousands of SNPs distributed throughout the alfalfa genome covering a broad range of GO categories. Validated SNPs represent valuable molecular marker resources that can be used to enhance marker density in linkage maps, identify potential factors involved in heterosis and genetic variation, and as tools for association mapping and genomic selection in alfalfa.
Identification of two linear B-cell epitopes from West Nile virus NS1 by screening a phage-displayed random peptide library
Authors: Sun En-Cheng , Ma Jian-Nan , Liu Ni-Hong , Yang Tao , Zhao Jing , Geng Hong-Wei , Wang Ling-Feng , Qin Yong-Li , Bu Zhi-Gao , Yang Yin-Hui , Lunt Ross A , Wang Lin-Fa , Wu Dong-Lai 
Published: July 2011

Abstract

Background
The West Nile virus (WNV) nonstructural protein 1 (NS1) is an important antigenic protein that elicits protective antibody responses in animals and can be used for the serological diagnosis of WNV infection. Although previous work has demonstrated the vital role of WNV NS1-specific antibody responses, the specific epitopes in the NS1 have not been identified.

Results
The present study describes the identification of two linear B-cell epitopes in WNV NS1 through screening a phage-displayed random 12-mer peptide library with two monoclonal antibodies (mAbs) 3C7 and 4D1 that directed against the NS1. The mAbs 3C7 and 4D1 recognized phages displaying peptides with the consensus motifs LTATTEK and VVDGPETKEC, respectively. Exact sequences of both motifs were found in the NS1 (895LTATTEK901 and 925VVDGPETKEC934). Further identification of the displayed B cell epitopes were conducted using a set of truncated peptides expressed as MBP fusion proteins. The data indicated that 896TATTEK901 and925VVDGPETKEC934 are minimal determinants of the linear B cell epitopes recognized by the mAbs 3C7 and 4D1, respectively. Antibodies present in the serum of WNV-positive horses recognized the minimal linear epitopes in Western blot analysis, indicating that the two peptides are antigenic in horses during infection. Furthermore, we found that the epitope recognized by 3C7 is conserved only among WNV strains, whereas the epitope recognized by 4D1 is a common motif shared among WNV and other members of Japanese encephalitis virus (JEV) serocomplex.

Conclusions
We identified TATTEK and VVDGPETKEC as NS1-specific linear B-cell epitopes recognized by the mAbs 3C7 and 4D1, respectively. The knowledge and reagents generated in this study may have potential applications in differential diagnosis and the development of epitope-based marker vaccines against WNV and other viruses of JEV serocomplex.
Parent satisfaction with a pediatric practice in Germany: A questionnaire-based study
Authors: Weissenstein Anne , Straeter Alexandra , Villalon Gloria , Luchter Elisabeth , Bittmann Stefan 
Published: July 2011

AbstractBackgroundParental satisfaction with a pediatric day center is essential for the medical treatment of children, since it is closely related to compliance. In order to ascertain factors which predict parental satisfaction as well as to discover possible weak points, we developed a questionnaire.Methods127 parents visiting the pediatric day center from October to November 2010 were asked to respond to a questionnaire. The survey was given to them directly by the doctor after their visit and it provided the opportunity to determine subjective and soft factors in quality management, which is essential for a pediatric practice. The questionnaire consisted of 27 items divided into three scales. The scales were as follows: satisfaction concerning the infrastructure and organization, satisfaction concerning the communicative and empathic competence of the doctor as well as the other staff, and finally the results and the overall impression. Moreover, the survey asked the respondents for their comments on the pediatric day center and sociodemographic data were queried.ResultsA total of 67 parents (52,7%) responded to the survey. The mean parental satisfaction concerning infrastructure and organization achieved 3,61 (scale 1-very unsatisfied-through 4-very satisfied). The mean satisfaction with the expertise of the doctor and the staff was 3,56 and the overall satisfaction was 3,65. Ninety-one percent of the parents would visit the pediatric practice again and 84,2% would definitely recommend the practice to others.ConclusionSurveys on parental satisfaction are essential for the success of a pediatric day center. Apart from the doctors abilities to interact with the parents, other factors, such as a short waiting period, a friendly and helpful staff, as well as appealing premises are essential for a high overall level of satisfaction.