The filtering, clear-cornea diathermal keratostomy: a minor Danish multicenter study

DEFF Research Database (Denmark)

Kessing, S.V.; Nissen, O.I.; Thygesen, J.

2008-01-01

PURPOSE: Is the new micropenetrating, clear-cornea procedure, intrastromal diathermal keratostomy (IDK), an alternative to the intricate "modern trabeculectomy"? METHODS: Prospective multicenter study. Four surgeons from 4 Danish eye departments attended an IDK course and subsequently decided whe...

Participation of a coordinating center pharmacy in a multicenter international study.

Science.gov (United States)

Jeon, Jihyun Esther; Mighty, Janet; Lane, Karen; McBee, Nichol; Majkowski, Ryan; Mayo, Steven; Hanley, Daniel

2016-11-15

The activities of a coordinating center pharmacy (CCP) supporting a multicenter, international clinical trial are described. Serving in a research support role comparable to that of a commercial clinical trial supply company, a CCP within the Johns Hopkins Hospital Investigational Drug Service (JHH IDS) uses its management expertise and infrastructure to support multicenter trials, such as the recently completed Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage, Phase III (CLEAR III) trial. The role of the CCP staff in supporting the CLEAR III trial was overall investigational product (IP) management through coordination of IP-related operations to ensure high-quality care for study participants at study sites in the United States and abroad. For the CLEAR III trial, the CCP coordinated IP supply activities; provided education to site pharmacists; developed study-specific documents, including pharmacy manuals; communicated with trial stakeholders, including third-party IP distributors; monitored treatment assignments; and performed quality assurance monitoring to ensure compliance with institutional, state, federal, and international regulations regarding IP procurement and storage. Acting as a CCP for a multicenter international study poses a number of operational challenges while providing opportunities for the CCP to contribute to research of global importance and enrich the skill sets of its personnel. The development and implementation of the CCP at JHH IDS for the CLEAR III trial included several responsibilities, such as IP supply management, communication, and database, regulatory, and finance management. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

An open multicenter study of polyacrylamide hydrogel (Bulkamid®) for female stress and mixed urinary incontinence

DEFF Research Database (Denmark)

Lose, Gunnar; Sørensen, Helle Christina; Axelsen, Susanne Maigaard

2010-01-01

Polyacrylamide hydrogel (PAHG, Bulkamid®) is a promising urethral bulking agent. This multicenter study was carried out to evaluate safety and efficacy of Bulkamid® for female stress and mixed urinary incontinence.......Polyacrylamide hydrogel (PAHG, Bulkamid®) is a promising urethral bulking agent. This multicenter study was carried out to evaluate safety and efficacy of Bulkamid® for female stress and mixed urinary incontinence....

The SPIRIT V study: a clinical evaluation of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo coronary artery lesions.

Science.gov (United States)

Grube, Eberhard; Chevalier, Bernard; Smits, Peter; Džavík, Vladimir; Patel, Tejas M; Mullasari, Ajit S; Wöhrle, Jochen; Stuteville, Marrianne; Dorange, Cécile; Kaul, Upendra

2011-02-01

The SPIRIT V (A Clinical Evaluation of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With De Novo Coronary Artery Lesions) study is a post-market surveillance experience of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) in patients with higher-risk coronary anatomy. Previous pre-approval studies have shown the safety and efficacy of EES in highly selected groups of patients. The SPIRIT V trial is a prospective, open label, single arm, multicenter study. Two thousand seven hundred patients with multiple de novo coronary artery lesions suitable for treatment with a planned maximum of 4 EES were enrolled at 93 centers in Europe, Asia Pacific, Canada, and South Africa. Lesions had a reference vessel diameter between 2.25 and 4.0 mm and a length of ≤ 28 mm by visual estimation. An independent clinical events committee adjudicated all end point-related events. The primary end point was the composite rate of all death, myocardial infarction (MI), and target vessel revascularization at 30 days. Secondary end points included stent thrombosis and acute success (clinical device and procedure success). At 30 days, the primary composite end point of all death, MI, and target vessel revascularization was 2.7%. At 1 year, rates of cardiac death, overall MI, and target lesion revascularization were 1.1%, 3.5%, and 1.8%, respectively. The cumulative rate of definite and probable stent thrombosis was low at 0.66% at 1 year. Use of EES in patients with multiple, complex de novo lesions yielded 1-year major adverse cardiac events, stent thrombosis, and target lesion revascularization rates that are comparable to those of the more controlled SPIRIT II and SPIRIT III trials-which included patients with restricted inclusion/exclusion criteria-and other all-comer population, physician-initiated studies like the X-SEARCH (Xience Stent Evaluated At Rotterdam Cardiology Hospital) and COMPARE (A Randomized

Chest radiographic data acquisition and quality assurance in multicenter studies

International Nuclear Information System (INIS)

Cleveland, R.H.; Schluchter, M.; Easley, K.A.; Wood, B.P.; Berdon, W.E.; Boechat, M.I.; Meziane, M.; Mellins, R.B.; Norton, K.I.; Singleton, E.; Trautwein, L.

1997-01-01

Background. Multicenter studies rely on data derived from different institutions. Forms can be designed to standardize the reporting process allowing reliable comparison of data. Objective. The purpose of the report is to provide a standardized method, developed as a part of a multicenter study of vertically transmitted HIV, for assessing chest radiographic results. Materials and methods. Eight hundred and five infants and children were studied at five centers; 3057 chest radiographs were scored. Data were entered using a forced-choice, graded response for 12 findings. Quality assurance measures and inter-rater agreement statistics are reported. Results. The form used for reporting chest radiographic results is presented. Inter-rater agreement was moderate to high for most findings, with the best correlation reported for the presence of bronchovascular markings and/or reticular densities addressed as a composite question (kappa = 0.71). The presence of nodular densities (kappa 0.56) and parenchymal consolidation (kappa = 0.57) had moderate agreement. Agreement for lung volume was low. Conclusion. The current tool, developed for use in the pediatric population, is applicable to any study involving the assessment of pediatric chest radiographs for a large population, whether at one or many centers. (orig.)

Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients

Directory of Open Access Journals (Sweden)

Alejandro Martin-Gorgojo

2018-03-01

Full Text Available The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

Combined "de novo" and "ex novo" lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis.

Science.gov (United States)

Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Qi, Gao-Xiang; Xiong, Lian; Lin, Xiao-Qing; Wang, Can; Li, Hai-Long; Chen, Xin-De

2017-01-01

Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways (" de novo " lipid fermentation and " ex novo " lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both " de novo " and " ex novo " lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined " de novo " and " ex novo " lipid fermentation by oleaginous yeast Trichosporon dermatis . Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis . Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis . The present study proves the potential and possibility of combined " de novo " and " ex novo " lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter Study.

Science.gov (United States)

Wang, Jeffrey C; Buser, Zorica; Fish, David E; Lord, Elizabeth L; Roe, Allison K; Chatterjee, Dhananjay; Gee, Erica L; Mayer, Erik N; Yanez, Marisa Y; McBride, Owen J; Cha, Peter I; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel

2017-04-01

A retrospective multicenter study. Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence. The purpose of this study was to determine the intraoperative mortality rates and associated risk factors in patients undergoing cervical spine surgery. Twenty-one surgical centers from the AOSpine North America Clinical Research Network participated in the study. Medical records of patients who received cervical spine surgery from January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of intraoperative death. A total of 258 patients across 21 centers met the inclusion criteria. Most of the surgeries were done using the anterior approach (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient age was 57.1 ± 13.2 years, and there were more male patients (54.7% male and 45.3% female). There was no case of intraoperative death. Death during cervical spine surgery is a very rare complication. In our multicenter study, there was a 0% mortality rate. Using an adequate surgical approach for patient diagnosis and comorbidities may be the reason how the occurrence of this catastrophic adverse event was prevented in our patient population.

Genes from scratch--the evolutionary fate of de novo genes.

Science.gov (United States)

Schlötterer, Christian

2015-04-01

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

Energy Technology Data Exchange (ETDEWEB)

Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

2015-03-01

Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

Sucralfate versus cimetidine in reflux esophagitis. A single-blind multicenter study

NARCIS (Netherlands)

Hameeteman, W.; v d Boomgaard, D. M.; Dekker, W.; Schrijver, M.; Wesdorp, I. C.; Tytgat, G. N.

1987-01-01

A single-blind randomized multicenter study was performed in 42 patients with endoscopically documented reflux esophagitis. Patients were randomly given 400 mg cimetidine q.i.d. or a suspension of 1 g sucralfate q.i.d. for a period of 8 weeks. Forty patients were evaluated after 8 weeks. Symptomatic

Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

Science.gov (United States)

Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

2017-01-01

In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Role of multicenter study groups for clinical research in hematology and oncology].

Science.gov (United States)

Gökbuget, N; Hoelzer, D

2009-04-01

During the past 25 years a highly effective infrastructure for clinical trials was developed in hematology. Following initial funding by the BMFT (Ministry for Research and Technology) a number of large multicenter study groups for leukemia and lymphoma were developed. Treatment results from these studies often represent the"gold standard". However, since no standard therapy is defined for these diseases, the study groups aim to treat all patients within treatment optimization trials (TOT) to combine research and care. They contribute considerably to quality control in therapy and diagnostics, e.g., by establishing central reference laboratories. The regulatory requirements for clinical trials were extended considerably after the activation of the 12th drug law and TOTs now have to fulfill requirements similar to registration trials in the pharmaceutical industry. Due to the considerable bureaucratic effort and increased costs, only few large multicenter trials could thereafter be initiated and a substantial disadvantage for independent academic research becomes clearly evident.

NovoPen Echo® insulin delivery device

Directory of Open Access Journals (Sweden)

Hyllested-Winge J

2016-01-01

Full Text Available Jacob Hyllested-Winge,1 Thomas Sparre,2 Line Kynemund Pedersen2 1Novo Nordisk Pharma Ltd, Tokyo, Japan; 2Novo Nordisk A/S, Søborg, Denmark Abstract: The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo® is one of the latest members of the NovoPen® family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders, who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. Keywords: NovoPen Echo®, memory function, half-unit increment dosing, adherence, children, adolescents 

A multicenter, long-term study on arrhythmias in children with Ebstein anomaly.

NARCIS (Netherlands)

Delhaas, T.; Sarvaas, G.J.; Rijlaarsdam, M.E.; Strengers, J.L.; Eveleigh, R.M.; Poulino, S.E.; Korte, C.L. de; Kapusta, L.

2010-01-01

To assess the prevalence, history, and treatment of arrhythmias, in particular preexcitation and Wolff-Parkinson-White (WPW) syndrome, in patients with Ebstein anomaly (EA) during childhood and adolescence, we performed a multicenter retrospective study of all consecutive live-born patients with EA,

A Multicenter, Long-Term Study on Arrhythmias in Children with Ebstein Anomaly

NARCIS (Netherlands)

Delhaas, Tammo; Sarvaas, Gideon J. du Marchie; Rijlaarsdam, Marry E.; Strengers, Jan L.; Eveleigh, Rhona M.; Poulino, Sumayah E.; de Korte, Chris L.; Kapusta, Livia

To assess the prevalence, history, and treatment of arrhythmias, in particular preexcitation and Wolff-Parkinson-White (WPW) syndrome, in patients with Ebstein anomaly (EA) during childhood and adolescence, we performed a multicenter retrospective study of all consecutive live-born patients with EA,

Segmentation of age-related white matter changes in a clinical multi-center study

DEFF Research Database (Denmark)

Dyrby, Tim B.; Rostrup, E.; Baare, W.F.C.

2008-01-01

Age-related white matter changes (WMC) are thought to be a marker of vascular pathology, and have been associated with motor and cognitive deficits. In the present study, an optimized artificial neural network was used as an automatic segmentation method to produce probabilistic maps of WMC...... in a clinical multi-center study. The neural network uses information from T1- and T2-weighted and fluid attenuation inversion recovery (FLAIR) magnetic resonance (MR) scans, neighboring voxels and spatial location. Generalizability of the neural network was optimized by including the Optimal Brain Damage (OBD......) pruning method in the training stage. Six optimized neural networks were produced to investigate the impact of different input information on WMC segmentation. The automatic segmentation method was applied to MR scans of 362 non-demented elderly subjects from 11 centers in the European multi-center study...

Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study.

LENUS (Irish Health Repository)

Unterscheider, Julia

2013-04-01

The objective of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction (IUGR) (PORTO Study), a national prospective observational multicenter study, was to evaluate which sonographic findings were associated with perinatal morbidity and mortality in pregnancies affected by growth restriction, originally defined as estimated fetal weight (EFW) <10th centile.

Particulated articular cartilage: CAIS and DeNovo NT.

Science.gov (United States)

Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

2012-03-01

Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

Peroral endoscopic myotomy for the treatment of achalasia: an international prospective multicenter study

NARCIS (Netherlands)

von Renteln, Daniel; Fuchs, Karl-Hermann; Fockens, Paul; Bauerfeind, Peter; Vassiliou, Melina C.; Werner, Yuki B.; Fried, Gerald; Breithaupt, Wolfram; Heinrich, Henriette; Bredenoord, Albert J.; Kersten, Jan F.; Verlaan, Tessa; Trevisonno, Michael; Rösch, Thomas

2013-01-01

Pilot studies have indicated that peroral endoscopic myotomy (POEM) might be a safe and effective treatment for achalasia. We performed a prospective, international, multicenter study to determine the outcomes of 70 patients who underwent POEM at 5 centers in Europe and North America. Three months

Quality of life after neck dissection. Multicenter study

International Nuclear Information System (INIS)

Nibu, Ken-ichi; Onitsuka, Tetsuo; Kawabata, Kazuyoshi

2010-01-01

To assess the impact of modifications to radical neck dissection and radiotherapy on the postoperative quality of life, the study group 'Study on Standardization of Treatment for Lymph Node Metastasis of Head and Neck Cancer' performed a multicenter cross-sectional study using our self-administered neck dissection questionnaire and arm abduction test. While sparing levels IV and V improved most postoperative symptoms, such as stiffness and constriction of the neck were avoided as long as the sternocleidmastoid muscle (SCM) and the spinal accessory nerve were preserved. Resection of the SCM and spinal accessory nerve resulted in a drop shoulder and neck pain, respectively. Irradiation with a total dose of 50 Gy or more worsened stiffness of neck and shoulder. (author)

Economic analysis of centralized vs. decentralized electronic data capture in multi-center clinical studies.

Science.gov (United States)

Walden, Anita; Nahm, Meredith; Barnett, M Edwina; Conde, Jose G; Dent, Andrew; Fadiel, Ahmed; Perry, Theresa; Tolk, Chris; Tcheng, James E; Eisenstein, Eric L

2011-01-01

New data management models are emerging in multi-center clinical studies. We evaluated the incremental costs associated with decentralized vs. centralized models. We developed clinical research network economic models to evaluate three data management models: centralized, decentralized with local software, and decentralized with shared database. Descriptive information from three clinical research studies served as inputs for these models. The primary outcome was total data management costs. Secondary outcomes included: data management costs for sites, local data centers, and central coordinating centers. Both decentralized models were more costly than the centralized model for each clinical research study: the decentralized with local software model was the most expensive. Decreasing the number of local data centers and case book pages reduced cost differentials between models. Decentralized vs. centralized data management in multi-center clinical research studies is associated with increases in data management costs.

Clinicopathologic factors associated with de novo metastatic breast cancer.

Science.gov (United States)

Shen, Tiansheng; Siegal, Gene P; Wei, Shi

2016-12-01

While breast cancers with distant metastasis at presentation (de novo metastasis) harbor significantly inferior clinical outcomes, there have been limited studies analyzing the clinicopathologic characteristics in this subset of patients. In this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to identify factors associated with de novo metastatic breast cancer. When compared to patients without metastasis at presentation, race, histologic grade, estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly associated with de novo metastasis in the entire cohort, whereas age, histologic grade, PR and HER2 status were the significant parameters in the subset of patients with locally advanced breast cancer (Stage IIB/III). The patients with de novo metastatic breast cancer had a significant older mean age and a lower proportion of HER2-positive tumors when compared to those with metastatic recurrence. Further, the HER2-rich subtype demonstrated a drastically higher incidence of de novo metastasis when compared to the luminal and triple-negative breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively] and in the patients with locally advanced disease (OR=4.02 and 2.12, respectively), whereas no significant difference was seen between de novo metastatic cancers and those with metastatic recurrence. Moreover, the luminal and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99) characteristics, respectively, for the sites of de novo metastasis, while the latter was not observed in those with metastatic recurrence. Our data suggest that an algorithm incorporating clinicopathologic factors, especially histologic grade and receptor profile, remains of significant benefit during decision making in newly diagnosed breast cancer in the pursuit of precision medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

Science.gov (United States)

Zago, Alexandre C; Matte, Bruno S; Reginato, Luciana; Iturry-Yamamoto, Germán; Krepsky, Ana; Bergoli, Luiz Carlos C; Balvedi, Julise; Raudales, José C; Saadi, Eduardo K; Zago, Alcides J

2012-01-01

Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study

OpenAIRE

Steihaug, Ole Martin; Gjesdal, Clara Gram; Bogen, Bård Erik; Kristoffersen, Målfrid Holen; Lien, Gunhild; Ranhoff, Anette Hylen

2017-01-01

Background: Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. Methods: A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory a...

Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

Lee SH

2015-02-01

Full Text Available Sang Hoon Lee,1 Seung Up Kim,1–3 Jeong Won Jang,4 Si Hyun Bae,4 Sanghun Lee,1,3 Beom Kyung Kim,1–3 Jun Yong Park,1–3 Do Young Kim,1–3 Sang Hoon Ahn,1–3 Kwang–Hyub Han1–31Department of Internal Medicine, 2Institute of Gastroenterology, Yonsei University College of Medicine, 3Liver Cirrhosis Clinical Research Center, 4Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, KoreaBackground/purpose: Liver stiffness (LS measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC. We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA.Methods: This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence.Results: This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months, 47 (42.3% patients experienced HCC de novo recurrence, and 18 (16.2% died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P<0.05. On multivariate analysis, together with previous anti-HCC treatment history, patients with LS values >13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR of 3.115 (95% confidence interval [CI], 1.238–7.842, P<0.05. Moreover, LS values independently predicted the mortality after RFA, with a HR of 9.834 (95% CI, 1.148–84.211, P<0.05, together with total bilirubin.Conclusions: Our

Performance of Ultrasound in the Diagnosis of Gout in a Multi-Center Study

DEFF Research Database (Denmark)

Ogdie, Alexis; Taylor, William J; Neogi, Tuhina

2017-01-01

OBJECTIVES: To examine the performance of ultrasound for the diagnosis of gout using presence of monosodium urate (MSU) crystals as the gold standard. METHODS: We analyzed data from the Study for Updated Gout Classification Criteria (SUGAR), a large, multi-center observational cross-sectional stu...

Foldability of a Natural De Novo Evolved Protein.

Science.gov (United States)

Bungard, Dixie; Copple, Jacob S; Yan, Jing; Chhun, Jimmy J; Kumirov, Vlad K; Foy, Scott G; Masel, Joanna; Wysocki, Vicki H; Cordes, Matthew H J

2017-11-07

The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo. Copyright © 2017 Elsevier Ltd. All rights reserved.

Descriptive epidemiology of the Multicenter ACL Revision Study (MARS) cohort.

Science.gov (United States)

Wright, Rick W; Huston, Laura J; Spindler, Kurt P; Dunn, Warren R; Haas, Amanda K; Allen, Christina R; Cooper, Daniel E; DeBerardino, Thomas M; Lantz, Brett Brick A; Mann, Barton J; Stuart, Michael J

2010-10-01

Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Cross-sectional study; Level of evidence, 2. After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most common mode of failure. Allograft graft choice is more common in the revision setting than autograft. Concomitant knee injury is extremely common in this population.

Precise detection of de novo single nucleotide variants in human genomes.

Science.gov (United States)

Gómez-Romero, Laura; Palacios-Flores, Kim; Reyes, José; García, Delfino; Boege, Margareta; Dávila, Guillermo; Flores, Margarita; Schatz, Michael C; Palacios, Rafael

2018-05-07

The precise determination of de novo genetic variants has enormous implications across different fields of biology and medicine, particularly personalized medicine. Currently, de novo variations are identified by mapping sample reads from a parent-offspring trio to a reference genome, allowing for a certain degree of differences. While widely used, this approach often introduces false-positive (FP) results due to misaligned reads and mischaracterized sequencing errors. In a previous study, we developed an alternative approach to accurately identify single nucleotide variants (SNVs) using only perfect matches. However, this approach could be applied only to haploid regions of the genome and was computationally intensive. In this study, we present a unique approach, coverage-based single nucleotide variant identification (COBASI), which allows the exploration of the entire genome using second-generation short sequence reads without extensive computing requirements. COBASI identifies SNVs using changes in coverage of exactly matching unique substrings, and is particularly suited for pinpointing de novo SNVs. Unlike other approaches that require population frequencies across hundreds of samples to filter out any methodological biases, COBASI can be applied to detect de novo SNVs within isolated families. We demonstrate this capability through extensive simulation studies and by studying a parent-offspring trio we sequenced using short reads. Experimental validation of all 58 candidate de novo SNVs and a selection of non-de novo SNVs found in the trio confirmed zero FP calls. COBASI is available as open source at https://github.com/Laura-Gomez/COBASI for any researcher to use. Copyright © 2018 the Author(s). Published by PNAS.

A Multicenter Study of the Presentation, Treatment, and Outcomes of Cervical Dural Tears.

Science.gov (United States)

O'Neill, Kevin R; Fehlings, Michael G; Mroz, Thomas E; Smith, Zachary A; Hsu, Wellington K; Kanter, Adam S; Steinmetz, Michael P; Arnold, Paul M; Mummaneni, Praveen V; Chou, Dean; Nassr, Ahmad; Qureshi, Sheeraz A; Cho, Samuel K; Baird, Evan O; Smith, Justin S; Shaffrey, Christopher; Tannoury, Chadi A; Tannoury, Tony; Gokaslan, Ziya L; Gum, Jeffrey L; Hart, Robert A; Isaacs, Robert E; Sasso, Rick C; Bumpass, David B; Bydon, Mohamad; Corriveau, Mark; De Giacomo, Anthony F; Derakhshan, Adeeb; Jobse, Bruce C; Lubelski, Daniel; Lee, Sungho; Massicotte, Eric M; Pace, Jonathan R; Smith, Gabriel A; Than, Khoi D; Riew, K Daniel

2017-04-01

Retrospective multicenter case series study. Because cervical dural tears are rare, most surgeons have limited experience with this complication. A multicenter study was performed to better understand the presentation, treatment, and outcomes following cervical dural tears. Multiple surgeons from 23 institutions retrospectively identified 21 rare complications that occurred between 2005 and 2011, including unintentional cervical dural tears. Demographic data and surgical history were obtained. Clinical outcomes following surgery were assessed, and any reoperations were recorded. Neck Disability Index (NDI), modified Japanese Orthopaedic Association (mJOA), Nurick classification (NuC), and Short-Form 36 (SF36) scores were recorded at baseline and final follow-up at certain centers. All data were collected, collated, and analyzed by a private research organization. There were 109 cases of cervical dural tears among 18 463 surgeries performed. In 101 cases (93%) there was no clinical sequelae following successful dural tear repair. There were statistical improvements ( P < .05) in mJOA and NuC scores, but not NDI or SF36 scores. No specific baseline or operative factors were found to be associated with the occurrence of dural tears. In most cases, no further postoperative treatments of the dural tear were required, while there were 13 patients (12%) that required subsequent treatment of cerebrospinal fluid drainage. Analysis of those requiring further treatments did not identify an optimum treatment strategy for cervical dural tears. In this multicenter study, we report our findings on the largest reported series (n = 109) of cervical dural tears. In a vast majority of cases, no subsequent interventions were required and no clinical sequelae were observed.

''de novo'' aneurysms following endovascular procedures

Energy Technology Data Exchange (ETDEWEB)

Briganti, F.; Cirillo, S.; Caranci, F. [Department of Neurological Sciences, Services of Neuroradiology, ' ' Federico II' ' University, Naples (Italy); Esposito, F.; Maiuri, F. [Department of Neurological Sciences, Services of Neurosurgery, ' ' Federico II' ' University, Naples (Italy)

2002-07-01

Two personal cases of ''de novo'' aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of ''de novo'' aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the ''de novo'' aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous ''de novo'' aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of ''de novo'' aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a ''de novo'' aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for ''de novo'' aneurysm formation. (orig.)

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

Science.gov (United States)

Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

2014-01-01

In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

Directory of Open Access Journals (Sweden)

Hui Miao

Full Text Available BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic. RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53 to 0.63 (95% CI, 0.60-0.66. CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

Study on Strategic Planning of Road and Bridge Infrastructure Development in City Planning: Taking Porto-novo City of Benin Republic as Example

Directory of Open Access Journals (Sweden)

Boko-haya Dossa Didier

2018-01-01

Full Text Available Concern about the townlet infrastructure construction in developing country is one of the crucial part of county town planning and development. By taking the overall planning and design in a case study of Porto-novo city at Republic of Benin, this paper analyzes the characteristics and opportunities of Porto-novo city and puts forward corresponding infrastructure construction strategy. In the end, the paper comes up with specific plan of planning and design under the background of Porto-novo's planning of development strategy.

Euclidean supergravity and multi-centered solutions

Directory of Open Access Journals (Sweden)

W.A. Sabra

2017-04-01

Full Text Available In ungauged supergravity theories, the no-force condition for BPS states implies the existence of stable static multi-centered solutions. The first solutions to Einstein–Maxwell theory with a positive cosmological constant describing an arbitrary number of charged black holes were found by Kastor and Traschen. Generalisations to five and higher dimensional theories were obtained by London. Multi-centered solutions in gauged supergravity, even with time-dependence allowed, have yet to be constructed. In this letter we construct supersymmetry-preserving multi-centered solutions for the case of D=5, N=2 Euclidean gauged supergravity coupled to an arbitrary number of vector multiplets. Higher dimensional Einstein–Maxwell multi-centered solutions are also presented.

Simplified Therapeutic Intervention Scoring System : The TISS-28 items - Results from a multicenter study

NARCIS (Netherlands)

Miranda, DR; deRijk, A; Schaufeli, W

Objectives: To validate a simplified version of the Therapeutic Intervention Scoring System, the TISS-28, and to determine the association of TISS-28 with the time spent on scored and nonscored nursing activities. Design: Prospective, multicenter study. Setting: Twenty-two adult medical, surgical,

Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study

OpenAIRE

Marie Sylvianne Rabodoarivelo; A Brandao; M C Cergole Novella; A G C. Bombonatte; B Imperiale; N Rakotosamimanana; N Morcillo; V Rasolofo; J C Palomino; A Martin

2018-01-01

Background: In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance. Methods: This was a multicenter study. Molecular detection of ...

Neointimal Healing Evaluated by Optical Coherence Tomography after Drug-Eluting Absorbable Metal Scaffold Implantation in de novo Native Coronary Lesions: Rationale and Design of the Magmaris-OCT Study.

Science.gov (United States)

Karjalainen, Pasi; Paana, Tuomas; Sia, Jussi; Nammas, Wail

We sought to explore neointimal healing assessed by optical coherence tomography (OCT) following implantation of the Magmaris sirolimus-eluting absorbable metal scaffold. The Magmaris-OCT is a prospective, multicenter, single-arm observational clinical study, intended to enrol 60 consecutive patients with up to 2 de novo native coronary lesions, each located in different major epicardial vessels, with a reference vessel diameter of 2.5-3.5 mm, and a maximum lesion length of 20 mm. Patients will undergo Magmaris scaffold implantation in the target lesion, according to the standard practice. Clinical follow-up will take place at 30 days, and at 3, 6, 9, and 12 months. For invasive-imaging follow-up, patients will be classified into 3 groups: cohort A will be scheduled for follow-up at 3 months, cohort B at 6 months, and cohort C at 12 months. Invasive imaging will include quantitative coronary angiography, OCT evaluation, and coronary flow reserve measurement. The primary end point will be the percentage of uncovered scaffold struts assessed by OCT at the prespecified follow-up. This study will provide insight into the short- and mid-term healing properties following Magmaris scaffold implantation, with special emphasis on the neointimal coverage of scaffold struts. © 2017 S. Karger AG, Basel.

Defining the maize transcriptome de novo using deep RNA-Seq

Energy Technology Data Exchange (ETDEWEB)

Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

2011-06-01

De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

Defining the maize transcriptome de novo using deep RNA-Seq

Energy Technology Data Exchange (ETDEWEB)

Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

2011-06-02

De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

Acute necrotizing pancreatitis: a multicenter study.

Science.gov (United States)

Fernández-Cruz, L; Navarro, S; Valderrama, R; Sáenz, A; Guarner, L; Aparisi, L; Espi, A; Jaurietta, E; Marruecos, L; Gener, J

1994-04-01

A multicenter study of acute necrotizing pancreatitis (ANP) classified in accordance with the Balthazar criteria (grades D and E), has been performed in 12 teaching hospitals. A total of 233 patients were reviewed, and the mortality rate was 26.6%. The most common etiology was biliary pancreatitis (45.5%). Among the complications, shock, renal insufficiency, pulmonary insufficiency and hemorrhagic gastritis were associated with a mortality rate of 51-66%. Diffuse fluid collections were associated with a higher mortality rate (26.8%) than localized fluid collections (14.5%). In 106 patients with gallstone pancreatitis, early surgery was performed in 17, and 5 patients (29.4%) died. No mortality was observed in 32 patients with delayed surgery. Sphincterotomy was performed in 13 patients, and 4 (30.7%) died. Early surgery (necrosectomy and closed peritoneal lavage) was undertaken in 75 patients, with a mortality rate of 39%. In conclusion, the morbidity and mortality rates of ANP can be improved with proper monitoring, adequate supportive care and the judicious use of surgery based on clinical and morphological findings.

Conducting multicenter research in healthcare simulation: Lessons learned from the INSPIRE network.

Science.gov (United States)

Cheng, Adam; Kessler, David; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay M; Hunt, Elizabeth A; Duval-Arnould, Jordan; Lin, Yiqun; Pusic, Martin; Auerbach, Marc

2017-01-01

Simulation-based research has grown substantially over the past two decades; however, relatively few published simulation studies are multicenter in nature. Multicenter research confers many distinct advantages over single-center studies, including larger sample sizes for more generalizable findings, sharing resources amongst collaborative sites, and promoting networking. Well-executed multicenter studies are more likely to improve provider performance and/or have a positive impact on patient outcomes. In this manuscript, we offer a step-by-step guide to conducting multicenter, simulation-based research based upon our collective experience with the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE). Like multicenter clinical research, simulation-based multicenter research can be divided into four distinct phases. Each phase has specific differences when applied to simulation research: (1) Planning phase , to define the research question, systematically review the literature, identify outcome measures, and conduct pilot studies to ensure feasibility and estimate power; (2) Project Development phase , when the primary investigator identifies collaborators, develops the protocol and research operations manual, prepares grant applications, obtains ethical approval and executes subsite contracts, registers the study in a clinical trial registry, forms a manuscript oversight committee, and conducts feasibility testing and data validation at each site; (3) Study Execution phase , involving recruitment and enrollment of subjects, clear communication and decision-making, quality assurance measures and data abstraction, validation, and analysis; and (4) Dissemination phase , where the research team shares results via conference presentations, publications, traditional media, social media, and implements strategies for translating results to practice. With this manuscript, we provide a guide to conducting quantitative multicenter

Response monitoring in de novo patients with Parkinson's disease.

Directory of Open Access Journals (Sweden)

Rita Willemssen

Full Text Available BACKGROUND: Parkinson's disease (PD is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD". METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

Recurrent Laryngeal Nerve Palsy After Cervical Spine Surgery: A Multicenter AOSpine Clinical Research Network Study.

Science.gov (United States)

Gokaslan, Ziya L; Bydon, Mohamad; De la Garza-Ramos, Rafael; Smith, Zachary A; Hsu, Wellington K; Qureshi, Sheeraz A; Cho, Samuel K; Baird, Evan O; Mroz, Thomas E; Fehlings, Michael; Arnold, Paul M; Riew, K Daniel

2017-04-01

Multicenter retrospective study. To investigate the risk of symptomatic recurrent laryngeal nerve palsy (RLNP) following cervical spine surgery, to examine risk factors for its development, and to report its treatment and outcomes. A multicenter study from 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was performed. Each center screened for rare complications following cervical spine surgery, including RLNP. Patients were included if they underwent cervical spine surgery (levels from C2 to C7) between January 1, 2005 and December 31, 2011. Data were analyzed with regard to complication treatment and outcome. Cases were compared to a control group from the AOSpine CSM and CSM-I studies. Three centers reported 19 cases of RLNP from a cohort of 1345 patients. The reported incidence of RLNP ranged from 0.6% to 2.9% between these 3 centers. Fifteen patients (79%) in the RLNP group were approached from the left side. Ten patients (52.6%) required treatment for RLNP-6 required medical therapy (steroids), 1 interventional treatment (injection laryngoplasty), and 3 conservative therapy (speech therapy). When examining outcomes, 73.7% (14/19) of cases resolved completely, 15.8% (3/19) resolved with residual effects, and in 10.5% (2/19) of cases this could not be determined. In this multicenter study examining rare complications following cervical spine surgery, the risk of RLNP after cervical spine surgery ranged from 0.6% to 2.9% between centers. Though rare, it was found that 16% of patients may experience partial resolution with residual effects, and 74% resolve completely.

Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.

Science.gov (United States)

Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Nohr-Westphal, Constanze; Brockmann, Jens; Andrassy, Joachim; Reinke, Petra; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Pascher, Andreas; Illner, Wolf-Dieter; Banas, Bernhard; Jauch, Karl-Walter

2010-07-27

De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation.

Science.gov (United States)

Tedesco-Silva, Helio; Pescovitz, Mark D; Cibrik, Diane; Rees, Michael A; Mulgaonkar, Shamkant; Kahan, Barry D; Gugliuzza, Kristene K; Rajagopalan, P R; Esmeraldo, Ronaldo de M; Lord, Hélène; Salvadori, Maurizio; Slade, Jennifer M

2006-12-27

Phase II trials of FTY720, a novel immunomodulator, have shown promise in preventing rejection with both standard and reduced cyclosporine exposure. This study was designed to confirm those findings. This one-year, multicenter, randomized, phase III study in 696 de novo renal transplant patients compared FTY720 5 mg plus reduced-dose cyclosporine (RDC) or FTY720 2.5 mg plus full-dose cyclosporine (FDC) with mycophenolate mofetil (MMF) plus FDC. All patients received concomitant corticosteroid therapy without antibody induction. The primary efficacy composite endpoint was the incidence of first treated biopsy-proven acute rejection (treated BPAR), graft loss, death or premature study discontinuation at month 12. FTY720 2.5 mg plus FDC was demonstrated to be non-inferior to MMF plus FDC as the primary efficacy endpoint (30.8% and 30.6%) was comparable. The FTY720 5 mg plus RDC treatment regimen was discontinued due to an increased incidence of acute rejection episodes (primary endpoint 43.3%). FTY720 was associated with significantly lower creatinine clearance with a mean difference at 12 months between FTY720 2.5 mg plus FDC and MMF plus FDC of 8 ml/min. While FTY720 2.5 mg plus FDC yielded similar efficacy to MMF plus FDC, the FTY720 5 mg plus RDC did not allow a 50% reduction in cyclosporine exposure. The associated lower creatinine clearance indicated that FTY720 combined with cyclosporine provided no benefit over standard care.

Studies of kinematic elements in two multicenter sunspot groups

International Nuclear Information System (INIS)

Korobova, Z.B.

1983-01-01

Some features of kinematic elements (KE) in two multicenter sunspot groups were studied using Tashkent full-disc white light heliograms. KE and morphological elements do not reveal any relationship. A KE coincides with a unipolar or multipolar spot or with part of a spot. It may also contain an extended stream including several spots. Relation of KE to large-scale photospheric magnetic fields is less clear. The line of polarity reversal is, in most cases, the deviding line between two adjacent KE. At the same time, a KE can contain spots of both polarities. Sunspot trajectories in the leading polarity regions show the best similarity. Interactions of KE are greatly influenced by the meridional drift. (author)

Glucagon infusion increases rate of purine synthesis de novo in rat liver

International Nuclear Information System (INIS)

Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

1987-01-01

Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

de novo computational enzyme design.

Science.gov (United States)

Zanghellini, Alexandre

2014-10-01

Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

Science.gov (United States)

Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin

2016-08-01

To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group

NARCIS (Netherlands)

Ruzicka, T.; Bieber, T.; Schöpf, E.; Rubins, A.; Dobozy, A.; Bos, J. D.; Jablonska, S.; Ahmed, I.; Thestrup-Pedersen, K.; Daniel, F.; Finzi, A.; Reitamo, S.

1997-01-01

Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. We conducted a randomized, doubleblind, multicenter study

Direct Visualization of De novo Lipogenesis in Single Living Cells

Science.gov (United States)

Li, Junjie; Cheng, Ji-Xin

2014-10-01

Increased de novo lipogenesis is being increasingly recognized as a hallmark of cancer. Despite recent advances in fluorescence microscopy, autoradiography and mass spectrometry, direct observation of de novo lipogenesis in living systems remains to be challenging. Here, by coupling stimulated Raman scattering (SRS) microscopy with isotope labeled glucose, we were able to trace the dynamic metabolism of glucose in single living cells with high spatial-temporal resolution. As the first direct visualization, we observed that glucose was largely utilized for lipid synthesis in pancreatic cancer cells, which occurs at a much lower rate in immortalized normal pancreatic epithelial cells. By inhibition of glycolysis and fatty acid synthase (FAS), the key enzyme for fatty acid synthesis, we confirmed the deuterium labeled lipids in cancer cells were from de novo lipid synthesis. Interestingly, we also found that prostate cancer cells exhibit relatively lower level of de novo lipogenesis, but higher fatty acid uptake compared to pancreatic cancer cells. Together, our results demonstrate a valuable tool to study dynamic lipid metabolism in cancer and other disorders.

De novo origin of human protein-coding genes.

Directory of Open Access Journals (Sweden)

Dong-Dong Wu

2011-11-01

Full Text Available The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

De Novo Origin of Human Protein-Coding Genes

Science.gov (United States)

Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

2011-01-01

The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

DEFF Research Database (Denmark)

2014-01-01

in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p...... = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have...... analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1...

Bolting multicenter solutions

Energy Technology Data Exchange (ETDEWEB)

Bena, Iosif [Institut de Physique Théorique, Université Paris Saclay, CEA, CNRS, 91191 Gif-sur-Yvette Cedex (France); Bossard, Guillaume [Centre de Physique Théorique, Ecole Polytechnique, CNRS, Université Paris-Saclay, 91128 Palaiseau Cedex (France); Katmadas, Stefanos; Turton, David [Institut de Physique Théorique, Université Paris Saclay, CEA, CNRS, 91191 Gif-sur-Yvette Cedex (France)

2017-01-30

We introduce a solvable system of equations that describes non-extremal multicenter solutions to six-dimensional ungauged supergravity coupled to tensor multiplets. The system involves a set of functions on a three-dimensional base metric. We obtain a family of non-extremal axisymmetric solutions that generalize the known multicenter extremal solutions, using a particular base metric that introduces a bolt. We analyze the conditions for regularity, and in doing so we show that this family does not include solutions that contain an extremal black hole and a smooth bolt. We determine the constraints that are necessary to obtain smooth horizonless solutions involving a bolt and an arbitrary number of Gibbons-Hawking centers.

Carotid Artery Injury in Anterior Cervical Spine Surgery: Multicenter Cohort Study and Literature Review

OpenAIRE

H?rtl, Roger; Alimi, Marjan; Abdelatif Boukebir, Mohamed; Berlin, Connor D.; Navarro-Ramirez, Rodrigo; Arnold, Paul M.; Fehlings, Michael G.; Mroz, Thomas E.; Riew, K. Daniel

2017-01-01

Study Design: Retrospective study and literature review. Objective: To provide more comprehensive data about carotid artery injury (CAI) or cerebrovascular accident (CVA) related to anterior cervical spine surgery. Methods: We conducted a retrospective, multicenter, case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records of 17?625 patients who went through cervical spine surgery (levels from C2 to C7) between Januar...

[Information management in multicenter studies: the Brazilian longitudinal study for adult health].

Science.gov (United States)

Duncan, Bruce Bartholow; Vigo, Álvaro; Hernandez, Émerson; Luft, Vivian Cristine; Ahlert, Hubert; Bergmann, Kaiser; Mota, Eduardo

2013-06-01

Information management in large multicenter studies requires a specialized approach. The Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil - Brazilian Longitudinal Study for Adult Health) has created a Datacenter to enter and manage its data system. The aim of this paper is to describe the steps involved, including the information entry, transmission and management methods. A web system was developed in order to allow, in a safe and confidential way, online data entry, checking and editing, as well as the incorporation of data collected on paper. Additionally, a Picture Archiving and Communication System was implemented and customized for echocardiography and retinography. It stores the images received from the Investigation Centers and makes them available at the Reading Centers. Finally, data extraction and cleaning processes were developed to create databases in formats that enable analyses in multiple statistical packages.

Treatment of traumatic thoracolumbar spine fractures : A multicenter prospective randomized study of operative versus nonsurgical treatment

NARCIS (Netherlands)

Siebenga, Jan; Leferink, Vincent J. M.; Segers, Michiel J. M.; Elzinga, Matthijs J.; Bakker, Fred C.; Haarman, Henk J. Th. M.; Rommens, Pol M.; ten Duis, Henk-Jan; Patka, Peter

2006-01-01

Study Design. Multicenter prospective randomized trial. Objective. To test the hypotheses that thoracolumbar AO Type A spine fractures without neurologic deficit, managed with short-segment posterior stabilization will show an improved radiographic outcome and at least the same functional outcome as

A multi-method approach toward de novo glycan characterization: a Man-5 case study.

Science.gov (United States)

Prien, Justin M; Prater, Bradley D; Cockrill, Steven L

2010-05-01

Regulatory agencies' expectations for biotherapeutic approval are becoming more stringent with regard to product characterization, where minor species as low as 0.1% of a given profile are typically identified. The mission of this manuscript is to demonstrate a multi-method approach toward de novo glycan characterization and quantitation, including minor species at or approaching the 0.1% benchmark. Recently, unexpected isomers of the Man(5)GlcNAc(2) (M(5)) were reported (Prien JM, Ashline DJ, Lapadula AJ, Zhang H, Reinhold VN. 2009. The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap mass spectrometry (MS). J Am Soc Mass Spectrom. 20:539-556). In the current study, quantitative analysis of these isomers found in commercial M(5) standard demonstrated that they are in low abundance (2-aminobenzoic acid to detect and chromatographically resolve multiple M(5) isomers in bovine ribonuclease B. With this multi-method approach, we have the capabilities to comprehensively characterize a biotherapeutic's glycan array in a de novo manner, including structural isomers at >/=0.1% of the total chromatographic peak area.

A prospective, randomized multicenter study comparing APD and CAPD treatment

DEFF Research Database (Denmark)

Bro, S; Bjorner, J B; Tofte-Jensen, P

2000-01-01

, dialysis-related complications, dialysis-related expenses. RESULTS: The quality-of-life studies showed that significantly more time for work, family, and social activities was available to patients on APD compared to those on CAPD (p ...) treatment with respect to quality of life and clinical outcomes in relation to therapy costs. DESIGN: A prospective, randomized multicenter study. SETTING: Three Danish CAPD units. PATIENTS: Thirty-four adequately dialyzed patients with high or high-average peritoneal transport characteristics were included...... were assessed at baseline and after 6 months by the self-administered short-form SF-36 generic health survey questionnaire supplemented with disease- and treatment-specific questions. Therapy costs were compared by evaluating dialysis-related expenses. MAIN OUTCOME MEASURES: Quality-of-life parameters...

Test-retest and between-site reliability in a multicenter fMRI study.

Science.gov (United States)

Friedman, Lee; Stern, Hal; Brown, Gregory G; Mathalon, Daniel H; Turner, Jessica; Glover, Gary H; Gollub, Randy L; Lauriello, John; Lim, Kelvin O; Cannon, Tyrone; Greve, Douglas N; Bockholt, Henry Jeremy; Belger, Aysenil; Mueller, Bryon; Doty, Michael J; He, Jianchun; Wells, William; Smyth, Padhraic; Pieper, Steve; Kim, Seyoung; Kubicki, Marek; Vangel, Mark; Potkin, Steven G

2008-08-01

In the present report, estimates of test-retest and between-site reliability of fMRI assessments were produced in the context of a multicenter fMRI reliability study (FBIRN Phase 1, www.nbirn.net). Five subjects were scanned on 10 MRI scanners on two occasions. The fMRI task was a simple block design sensorimotor task. The impulse response functions to the stimulation block were derived using an FIR-deconvolution analysis with FMRISTAT. Six functionally-derived ROIs covering the visual, auditory and motor cortices, created from a prior analysis, were used. Two dependent variables were compared: percent signal change and contrast-to-noise-ratio. Reliability was assessed with intraclass correlation coefficients derived from a variance components analysis. Test-retest reliability was high, but initially, between-site reliability was low, indicating a strong contribution from site and site-by-subject variance. However, a number of factors that can markedly improve between-site reliability were uncovered, including increasing the size of the ROIs, adjusting for smoothness differences, and inclusion of additional runs. By employing multiple steps, between-site reliability for 3T scanners was increased by 123%. Dropping one site at a time and assessing reliability can be a useful method of assessing the sensitivity of the results to particular sites. These findings should provide guidance toothers on the best practices for future multicenter studies.

A Terra em Transe: o cosmopolitismo às avessas do cinema novo

Directory of Open Access Journals (Sweden)

Angela Prysthon

2008-11-01

Full Text Available Usando como referencial teórico os estudos culturais, este artigo analisa o cinema novo brasileiro como parte de uma estratégia terceiro mundista de conceber a cultura. A partir da emergência do conceito de terceiro mundo e das lutas de descolonização nos anos 1950 e 1960, a ideologia cosmopolita foi sendo vista pelos intelectuais de esquerda como a versão cultural da aliança com as forças hegemônicas da Europa e dos Estados Unidos. O projeto do cinema novo chama a atenção por suas afinidades ideológicas com o terceiro mundismo, mas, paradoxalmente, trazendo à tona uma polí­tica cosmopolita da periferia. Palavras-chave cinema novo, identidade, cultura brasileira, terceiro mundismo, estudos culturais. Abstract Using the cultural studies theoretical framework, this paper analyzes the cinema novo movement in Brazil as a part of the Third World conception of culture. Following the creation of the term "Third World" and the international politics of colonial independence of the 1950s and 1960s, a cosmopolitan attitude was seen by the intellectuals of the left as a cultural version of the alliance with the hegemonic forces of Europe and North America. Even though the cinema novo project can be associated with the ideology of an united Third World ,it brings about, paradoxically, a very cosmopolitan politics of the periphery. Key words cinema novo, identity, Brazilian culture, third world, cultural studies.

A randomized, controlled, multicenter trial to evaluate the safety and efficacy of Zotarolimus- vs. Paclitaxel-eluting stents in de novo occlusive lesions in coronary arteries

DEFF Research Database (Denmark)

Chevalier, Bernard; Dimario, Carlo; Neumann, Franz-Josef

2013-01-01

The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the pr...

A simple method suitable to study de novo root organogenesis

Directory of Open Access Journals (Sweden)

Xiaodong eChen

2014-05-01

Full Text Available De novo root organogenesis is the process in which adventitious roots regenerate from detached or wounded plant tissues or organs. In tissue culture, appropriate types and concentrations of plant hormones in the medium are critical for inducing adventitious roots. However, in natural conditions, regeneration from detached organs is likely to rely on endogenous hormones. To investigate the actions of endogenous hormones and the molecular mechanisms guiding de novo root organogenesis, we developed a simple method to imitate natural conditions for adventitious root formation by culturing Arabidopsis thaliana leaf explants on B5 medium without additive hormones. Here we show that the ability of the leaf explants to regenerate roots depends on the age of the leaf and on certain nutrients in the medium. Based on these observations, we provide examples of how this method can be used in different situations, and how it can be optimized. This simple method could be used to investigate the effects of various physiological and molecular changes on the regeneration of adventitious roots. It is also useful for tracing cell lineage during the regeneration process by differential interference contrast observation of -glucuronidase staining, and by live imaging of proteins labeled with fluorescent tags.

Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study

International Nuclear Information System (INIS)

Pokrajac, Boris; Poetter, Richard; Wolfram, Roswitha M.; Budinsky, Alexandra C.; Kirisits, Christian; Lileg, Brigitte; Mendel, Helmuth; Sabeti, Schila; Schmid, Rainer; Minar, Erich

2005-01-01

Background and purpose: The aim of the trial was to investigate the effect of Iridium-192 gamma endovascular brachytherapy on reduction of restenosis after femoropopliteal angioplasty. Patients and methods: Between Oct, 1998 and Jul, 2001 a total of 134 patients have been randomized after successful angioplasty to brachytherapy or sham irradiation in a prospective, randomized, multicenter, double blind controlled trial. Patients with de novo lesion of at least 5 cm or recurrent lesion of any length after prior angioplasty have been enrolled. Brachytherapy was performed with 7 F centering catheter. Mean lesion length was 9.1 cm (1.5-25 cm) and mean intervention length 13.6 cm (4-27.5 cm) in brachytherapy cohort. Results: In placebo cohort mean lesion length was 10.3 cm (2-25 cm) and mean intervention length 14.1 cm (2-29 cm). A dose of 18 Gy was prescribed 2 mm from the surface of centering balloons. Analyzed (based on angiography) on intention to treat basis the binary restenosis rate at 12 months was 41.7% (28/67) in brachytherapy cohort and 67.1% (45/67) in placebo cohort (χ 2 test, P 30% residual stenosis after angioplasty) have been 23.4% in the brachytherapy and 53.3% in the placebo group (P<0.05), respectively. The cumulative patency rates after 24 months on intention to treat analysis were 54% in the brachytherapy and 27% in the placebo group (P<0.005). Corresponding data for as treated analysis were 77% in the brachytherapy and 39% in the placebo group (P<0.001). Late thrombosis was not seen. Conclusions: Significant reduction of restenosis rate was obtained with endovascular gamma brachytherapy after femoropopliteal angioplasty

A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

Science.gov (United States)

Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

2016-08-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

Science.gov (United States)

Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

2015-01-01

Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

Science.gov (United States)

Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

2018-05-01

Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

A national multicenter registration study. Omalizumb in children in Denmark

DEFF Research Database (Denmark)

Spangberg, Katrien; Jørgensen, Inger Merete; Agertoft, Lone

Background: In Denmark, Omalizumab is approved to treat children with severe persistent allergic asthma older than 6 years of age. No systematic registration of the efficacy in the Danish child population according to asthma symptoms or of the efficacy on co-morbid allergic symptoms exists. Results...... from a pilot study show that a broad panel of outcome measures is necessary to evaluate the efficacy of Omalizumab treatment as no change in lung function could be demonstrated Aim: To provide a standardized systematic registration in order to create a database enrolling children with severe allergic...... asthma treated with Omalizumab. Method and study design: A national multicenter registration and follow-up study based on children with clinical persistent severe allergic asthma including both retrospective and prospective registration. Inclusion criteria: • 6-18 years of age. • Severe persistent...

Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study

DEFF Research Database (Denmark)

Gordh, Torsten E; Stubhaug, Audun; Jensen, Troels S

2008-01-01

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400mg/day. The study comprised a run...

Comparative Study for Efficacy and Safety of Adenoidectomy according to the Surgical Method: A Prospective Multicenter Study.

Directory of Open Access Journals (Sweden)

Jeong-Whun Kim

Full Text Available There have been several operative techniques for adenoidectomy and their efficacy and morbidity are different according to the technique. This prospective multicenter study was aimed to compare the efficacy and morbidity of coblation adenoidectomy (CA with those of power-assisted adenoidectomy.Prospective multi-institutional study.Children who underwent CA, power-assisted adenoidectomy with cauterization (PAA+C or without cauterization (PAA-C due to adenoid hypertrophy were enrolled from 13 hospitals between July 2013 and June 2014. Mean operation time, degree of intraoperative bleeding and postoperative bleeding rate were evaluated.A total of 388 children (mean age ± standard deviation = 6.6 ± 2.5 years; 245 males and 143 females were included. According to the adenoidectomy technique, the children were classified into 3 groups: (1 CA (n = 116; (2 PAA+C (n = 153; and (3 PAA-C (n = 119. Significant differences were not found in age and sex among three groups. In the CA group, mean operation time was significantly shorter (P < 0.001 and degree of intraoperative bleeding was significantly less (P < 0.001 compared to PAA+C or PAA-C group. Delayed postoperative bleeding rate of PAA-C group was significantly higher than that of CA or PAA+C group (P = 0.016.This prospective multicenter study showed that CA was superior to PAA in terms of mean operation time and degree of intraoperative bleeding.

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study.

Science.gov (United States)

Leal Reyna, Mariela; Gómez, Reynaldo M; Lupi, Susana N; Belli, Susana H; Fenili, Cecilia A; Martínez, Marcela S; Ruibal, Gabriela F; Rossi, María A; Chervin, Raúl A; Cornaló, Dora; Contreras, Liliana N; Costa, Liliana; Nofal, María T; Damilano, Sergio A; Pardes, Ester M

2015-10-01

Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study. We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined. According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively. This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Who Donates Their Body to Science? An International, Multicenter, Prospective Study

Science.gov (United States)

Cornwall, Jon; Perry, Gary F.; Louw, Graham; Stringer, Mark D.

2012-01-01

The altruistic act of body donation provides a precious resource for both teaching and researching human anatomy. However, relatively little is known about individuals who donate their bodies to science (donors), and in particular whether donors in different geographical locations share similar characteristics. A multicenter prospective survey of…

Airline Maintenance Manpower Optimization from the De Novo Perspective

Science.gov (United States)

Liou, James J. H.; Tzeng, Gwo-Hshiung

Human resource management (HRM) is an important issue for today’s competitive airline marketing. In this paper, we discuss a multi-objective model designed from the De Novo perspective to help airlines optimize their maintenance manpower portfolio. The effectiveness of the model and solution algorithm is demonstrated in an empirical study of the optimization of the human resources needed for airline line maintenance. Both De Novo and traditional multiple objective programming (MOP) methods are analyzed. A comparison of the results with those of traditional MOP indicates that the proposed model and solution algorithm does provide better performance and an improved human resource portfolio.

Elliptic genera from multi-centers

Energy Technology Data Exchange (ETDEWEB)

Gaddam, Nava [Institute for Theoretical Physics and Center for Extreme Matter and Emergent Phenomena,Utrecht University, 3508 TD Utrecht (Netherlands)

2016-05-13

I show how elliptic genera for various Calabi-Yau threefolds may be understood from supergravity localization using the quantization of the phase space of certain multi-center configurations. I present a simple procedure that allows for the enumeration of all multi-center configurations contributing to the polar sector of the elliptic genera — explicitly verifying this in the cases of the quintic in ℙ{sup 4}, the sextic in Wℙ{sub (2,1,1,1,1)}, the octic in Wℙ{sub (4,1,1,1,1)} and the dectic in Wℙ{sub (5,2,1,1,1)}. With an input of the corresponding ‘single-center’ indices (Donaldson-Thomas invariants), the polar terms have been known to determine the elliptic genera completely. I argue that this multi-center approach to the low-lying spectrum of the elliptic genera is a stepping stone towards an understanding of the exact microscopic states that contribute to supersymmetric single center black hole entropy in N=2 supergravity.

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study.

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Richard Hansen

Full Text Available Children presenting for the first time with inflammatory bowel disease (IBD offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates. Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae. No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312.This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.This study is publically registered on the United Kingdom Clinical Research Network Portfolio (9633.

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study

DEFF Research Database (Denmark)

Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

2010-01-01

Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated...... and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing...

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study

DEFF Research Database (Denmark)

Petersen, Esben; Mouridsen, Kim; Golay, Xavier

2009-01-01

Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated...... and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing...

The impact of employee satisfaction on productivity in Tiskarna Novo mesto, Ltd.

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Simona Cimperman

2016-06-01

Full Text Available Research Question: Does employee satisfaction, impact on productivity? How are these two variables associated? What is the job satisfaction in Tiskarna Novo mesto, Ltd. What needs to be done to make employees more satisfied at work and, consequently, more productive? Purpose: The purpose of the study is to determine what are the factors that influence employee satisfaction Tiskarna Novo mesto, Ltd. and check the connection between work satisfaction and employee productivity. The aim of the research is to examine what is the level of job satisfaction of employees in Tiskarna Novo mesto, Ltd. And find our reasons and factors that prevent employees were satisfied in the workplace. Method: In this study we used a descriptive method and the method of combining the study of domestic and foreign literature. Pending the results we have come to interview employees in the Tiskarna Novo mesto, Ltd. Results: We conducted a survey among employees in Tiskarna Novo mesto, Ltd and we came to the conclusion that the employees are medium satisfied – the average grade point job satisfaction of employees was 3.1 (evaluated on a 5-point Likert scale. The worst assessed was factor in job satisfaction opportunity for advancement and educational opportunities. We have found out that factors like receiving praise and awards as well as good interpersonal relations are those that affect good on job satisfaction, on the other hand conflict is the one that reduces job satisfaction. The existence of links between work satisfaction and productivity were not found (r = -0.061. Organization: The organization and managers, it is important to know which are the factors by which employees are satisfied or dissatisfied. Results of the research will give managers a clear picture of the factors of satisfaction / dissatisfaction and opinion on productivity. Society: The employees it means a lot to have your job satisfaction and consequently they are more productive. Originality: The

Report of a Brazilian multicenter study on nephropathic cystinosis.

Science.gov (United States)

Vaisbich, Maria Helena; Koch, Vera H

2010-01-01

The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança--HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment. To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications. Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams. We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal - HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors' offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10

Novos paradigmas literários

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Denise Azevedo Duarte Guimarães

2005-12-01

Full Text Available O artigo estuda a emergência de novos paradigmas literários, procurando refletir acerca das textualidades contemporâneas. Focaliza os hipertextos informatizados e a poesia multimídia, com o intuito de desvendar como estão sendo criados novos procedimentos expressivos e em que medida eles podem ser identificados com reflexões teóricas anteriores acerca do texto literário impresso. Remete a questões ligadas à leitura dos diferentes tipos de signos e aos modos como eles se integram para a constituição dessas novíssimas linguagens híbridas em novos suportes.El artículo estudia la emergencia de nuevos paradigmas literarios, procurando reflejar acerca de las textualidades contemporáneas. Enfoca los hipertextos informatizados y la poesía multimedia, intentando desvendar cómo están siendo creados nuevos procedimientos expresivos y en qué medida ellos pueden ser identificados a reflexiones teóricas anteriores acerca del texto literario impreso. Remite a cuestiones ligadas a la lectura de los diferentes tipos de signos y a los modos cómo ellos se interaccionan para la constitución de los novísimos lenguajes híbridos en nuevos supuestos.This article investigates the emergence of new literary paradigms as it tries to understand new contemporary textualities. It analyses some hypertexts and multimedia poetry trying to trace how new expressive procedures are being created. How can these new languages be identified and what are their relations to previous theories which dealt with the literary printed text? This study approaches questions linked to the reading of different types of signs and the modes they function towards the fabrication of these new hybrid languages.

Genome-wide patterns and properties of de novo mutations in humans

NARCIS (Netherlands)

Francioli, Laurent C.; Polak, Paz P.; Koren, Amnon; Menelaou, Androniki; Chun, Sung; Renkens, Ivo; van Duijn, Cornelia M.; Swertz, Morris; Wijmenga, Cisca; van Ommen, Gertjan; Slagboom, P. Eline; Boomsma, Dorret I.; Ye, Kai; Guryev, Victor; Arndt, Peter F.; Kloosterman, Wigard P.; de Bakker, Paul I. W.; Sunyaev, Shamil R.

Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect(1-10). Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring

Genome-wide patterns and properties of de novo mutations in humans

NARCIS (Netherlands)

Francioli, L.C.; Polak, P.P.; Koren, A.; Menelaou, A.; Chun, S.; Renkens, I.; van Duijn, C.M.; Swertz, M.A.; Wijmenga, C.; van Ommen, G.J.; Slagboom, P.E.; Boomsma, D.I.; Ye, K.; Guryev, V.; Arndt, P.F.; Kloosterman, W.P.; Bakker, P.I.W.; Sunyaev, S.R.; Dijk, F.; Neerincx, P.B.T.; Pulit, S.L.; Deelen, P.; Elbers, C.C.; Palamara, P.F.; Pe'er, I.; Abdellaoui, A.; van Oven, M.; Vermaat, M.; Li, M.; Laros, J.F.J.; Stoneking, M.; de Knijff, P.; Kayser, M.; Veldink, J.H.; Van den Berg, L.H.; Byelas, H.; den Dunnen, J.T.; Dijkstra, M.; Amin, N.; van der Velde, K.J.; Hottenga, J.J.; van Setten, J.; van Leeuwen, E.M.; Kanterakis, A.; Kattenberg, V.M.; Karssen, L.C.; van Schaik, B.D.C.; Bot, J.; Nijman, I.J.; van Enckevort, D.; Mei, H.; Koval, V.; Estrada, K.; Medina-Gomez, C.; Lameijer, E.W.; Moed, M.H.; Hehir-Kwa, J.Y.; Handsaker, R.E.; McCarroll, S.A.; Vuzman, D.; Sohail, M.; Hormozdiari, F.; Marschall, T.; Schönhuth, A.; Beekman, M.; de Craen, A.J.; Suchiman, H.E.D.; Hofman, A.; Oostra, B.; Isaacs, A.; Rivadeneira, F.; Uitterlinden, A.G.; Willemsen, G.; Platteel, M.; Pitts, S.J.; Potluri, S.; Sundar, P.; Cox, D.R.; Li, Q.; Li, Y.; Du, Y.; Chen, R.; Cao, H.; Li, N.; Cao, S.; Wang, J.; Bovenberg, J.A.; Brandsma, M.

2015-01-01

Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of

Role of de novo biosynthesis in ecosystem scale monoterpene emissions from a boreal Scots pine forest

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R. Taipale

2011-08-01

Full Text Available Monoterpene emissions from Scots pine have traditionally been assumed to originate as evaporation from specialized storage pools. More recently, the significance of de novo emissions, originating directly from monoterpene biosynthesis, has been recognized. To study the role of biosynthesis at the ecosystem scale, we measured monoterpene emissions from a Scots pine dominated forest in southern Finland using the disjunct eddy covariance method combined with proton transfer reaction mass spectrometry. The interpretation of the measurements was based on a correlation analysis and a hybrid emission algorithm describing both de novo and pool emissions. During the measurement period May–August 2007, the monthly medians of daytime emissions were 200, 290, 180, and 200 μg m⁻² h⁻¹. The emissions were partly light dependent, probably due to de novo biosynthesis. The emission potential for both de novo and pool emissions exhibited a decreasing summertime trend. The ratio of the de novo emission potential to the total emission potential varied between 30 % and 46 %. Although the monthly changes were not significant, the ratio always differed statistically from zero, suggesting that the role of de novo biosynthesis was observable. Given the uncertainties in this study, we conclude that more accurate estimates of the contribution of de novo emissions are required for improving monoterpene emission algorithms for Scots pine dominated forests.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - A multicenter prospective comparative study

DEFF Research Database (Denmark)

Antonsen, Sofie Leisby; Jensen, Lisa Neerup; Loft, Annika

2012-01-01

OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when...

Recurrence risk in de novo structural chromosomal rearrangements.

Science.gov (United States)

Röthlisberger, Benno; Kotzot, Dieter

2007-08-01

According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

Endovascular gamma-irradiation for prevention of restenosis after angioplasty of femoropopliteal de-novo-stenoses. Long-term results of a feasibility study

International Nuclear Information System (INIS)

Krueger, K.; Zaehringer, M.; Schulte, O.; Lackner, K.; Bendel, M.; Bongartz, R.; Nolte, M.

2002-01-01

Objectives: To evaluate the performance and efficacy of endovascular irradiation after percutaneous transluminal angioplasty (PTA) of de-novo femoropopliteal stenoses in a pilot study. Methods: 6 patients received non-centered endovascular irradiation (12 Gray at surface of the vessel wall) immediately after angioplasty of de-novo femoropopliteal stenosis, 1 patient was given centered endovascular irradiation using 192-iridium (12 Gray at surface of the vessel wall) Centered irradiation was considered for two other patients. Duplex sonographies and interviews were performed the day before and after PTA and after 1, 3, 6, 9, 12, 18, 24 months up to 4 years. Intraarterial angiography was performed in symptomatic patients. Results: Non-centered endovascular irradiation was possible in all patiens without problems or complications. Centered irradiation was not possible in two patients with the cross-over approach. One thromboembolic complication occurred during centered irradiation. Both restenosis and new stenosis at the edge of irradiated distance occurred in 1/7 patiens. No other side effects were observed during follow-up. Conclusions: In our pilot study endovascular irradiation after angioplasty of de-novo femoropopliteal stenosis was possible with low rates of complications and restenosis and taking vessel anatomy into account. (orig.) [de

Research priorities for a multi-center child abuse pediatrics network - CAPNET.

Science.gov (United States)

Lindberg, Daniel M; Wood, Joanne N; Campbell, Kristine A; Scribano, Philip V; Laskey, Antoinette; Leventhal, John M; Pierce, Mary Clyde; Runyan, Desmond K

2017-03-01

Although child maltreatment medical research has benefited from several multi-center studies, the new specialty of child abuse pediatrics has not had a sustainable network capable of pursuing multiple, prospective, clinically-oriented studies. The Child Abuse Pediatrics Network (CAPNET) is a new multi-center research network dedicated to child maltreatment medical research. In order to establish a relevant, practical research agenda, we conducted a modified Delphi process to determine the topic areas with highest priority for such a network. Research questions were solicited from members of the Ray E. Helfer Society and study authors and were sorted into topic areas. These topic areas were rated for priority using iterative rounds of ratings and in-person meetings. The topics rated with the highest priority were missed diagnosis and selected/indicated prevention. This agenda can be used to target future multi-center child maltreatment medical research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Melhoramento do cafeeiro: IV - Café Mundo Novo

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A. Carvalho

1952-06-01

plants from progenies grown in Campinas and the murta variety (ttNana grave indication that these plants are of the bourbon type (ttNaNa and not of the typica type (TTNaNa, as it is the case of the ordinary Sumatra coffee. It has been assumed, therefore, that the Mundo Novo coffee probably originated from a primitive natural cross between the imported Sumatra coffee and the bourbon variety, already existent in the State of São Paulo when the Sumatra coffee was introduced. The progenies of Mundo Novo coffee here studied present a majority of vigorous and productive plants and a few weak individuals with very low productivity. Total yield per plant and per progeny were analized and discussed, for the period from 1946 to 1951. It is apparent that some progenies behave equally well in all locations and that high yield variability between plants is found in all Experiment Stations. The Mundo Novo coffee does not differ from other varieties in the percentages of the commercial seed types, namely, the normal flat beans, the peaberry type, and those resulting from the simultaneous development of two or more ovules in the same fruit locule. It was found, however, that a large percentage of Mundo Novo plants regularly produce an abnormal quantity of fruits with one or two empty locules. This constitutes a defect of the Mundo Novo coffee, which probably can be overcome by selection. It seems that this defect, which is not correlated with yield, is detenruned by genetic factors. Progenies are found where the number of plants showing unusual amounts of empty fruit locules is very low, other plants being normal is this respect. The most promising Mundo Novo plants from several progenies have already been artificially self-pollinated, and the seeds thus obtained were used to plant foundation seed plots. Within a few years seeds of selected Mundo Novo coffee plants will be available to farmers in the State of São Paulo.

Diagnostic performance of computed tomography coronary angiography (from the Prospective National Multicenter Multivendor EVASCAN Study).

Science.gov (United States)

Gueret, Pascal; Deux, Jean-François; Bonello, Laurent; Sarran, Anthony; Tron, Christophe; Christiaens, Luc; Dacher, Jean-Nicolas; Bertrand, David; Leborgne, Laurent; Renard, Cedric; Caussin, Christophe; Cluzel, Philippe; Helft, Gerard; Crochet, Dominique; Vernhet-Kovacsik, Hélène; Chabbert, Valérie; Ferrari, Emile; Gilard, Martine; Willoteaux, Serge; Furber, Alain; Barone-Rochette, Gilles; Jankowski, Adrien; Douek, Philippe; Mousseaux, Elie; Sirol, Marc; Niarra, Ralph; Chatellier, Gilles; Laissy, Jean-Pierre

2013-02-15

Computed tomographic coronary angiography (CTCA) has been proposed as a noninvasive test for significant coronary artery disease (CAD), but only limited data are available from prospective multicenter trials. The goal of this study was to establish the diagnostic accuracy of CTCA compared to coronary angiography (CA) in a large population of symptomatic patients with clinical indications for coronary imaging. This national, multicenter study was designed to prospectively evaluate stable patients able to undergo CTCA followed by conventional CA. Data from CTCA and CA were analyzed in a blinded fashion at central core laboratories. The main outcome was the evaluation of patient-, vessel-, and segment-based diagnostic performance of CTCA to detect or rule out significant CAD (≥50% luminal diameter reduction). Of 757 patients enrolled, 746 (mean age 61 ± 12 years, 71% men) were analyzed. They underwent CTCA followed by CA 1.7 ± 0.8 days later using a 64-detector scanner. The prevalence of significant CAD in native coronary vessels by CA was 54%. The rate of nonassessable segments by CTCA was 6%. In a patient-based analysis, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of CTCA were 91%, 50%, 68%, 83%, 1.82, and 0.18, respectively. The strongest predictors of false-negative results on CTCA were high estimated pretest probability of CAD (odds ratio [OR] 1.97, p <0.001), male gender (OR 1.5, p <0.002), diabetes (OR 1.5, p <0.0001), and age (OR 1.2, p <0.0001). In conclusion, in this large multicenter study, CTCA identified significant CAD with high sensitivity. However, in routine clinical practice, each patient should be individually evaluated, and the pretest probability of obstructive CAD should be taken into account when deciding which method, CTCA or CA, to use to diagnose its presence and severity. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease

DEFF Research Database (Denmark)

Paludan-Müller, Christian; Ahlberg, Gustav; Ghouse, Jonas

2017-01-01

BACKGROUND: De novo variants in the exome occur at a rate of 1 per individual per generation, and because of the low reproductive fitness for de novo variants causing severe disease, the likelihood of finding these as standing variations in the general population is low. Therefore, this study...... sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database. METHODS AND RESULTS: We performed a literature search for previous publications on de novo variants associated with severe arrhythmias...... trio studies (>1000 subjects). Of the monogenic variants, 11% (23/211) were present in ExAC, whereas 26% (802/3050) variants believed to increase susceptibility of disease were identified in ExAC. Monogenic de novo variants in ExAC had a total allele count of 109 and with ≈844 expected cases in Ex...

De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

Science.gov (United States)

Lenihan, Colin R; Liu, Sai; Deswal, Anita; Montez-Rath, Maria E; Winkelmayer, Wolfgang C

2018-03-29

Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. Retrospective observational cohort study. Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality. Copyright © 2018

Coordination of international multicenter studies: governance and administrative structure Coordinación de estudios multicéntricos internacionales: estructura administrativa y reglamentación

Directory of Open Access Journals (Sweden)

Shrikant I. Bangdiwala

2003-01-01

Full Text Available A well-conducted multicenter study needs to assure standardization, uniformity of procedures, high data quality, and collaboration across sites. This manuscript describes the organization and dynamics of multicenter studies, focusing on governance and administrative structures among countries of diverse cultures. The organizational structure of a multicenter study is described, and a system for oversight and coordination, along with roles and responsibilities of participants in the multicenter study, are presented. The elements of a governance document are also reviewed, along with guidelines and policies for effective collaboration. The experience of an ongoing multi-country collaboration, the World Studies of Abuse in the Family Environment (WorldSAFE, illustrates the implementation of these guidelines. It is essential that multicenter studies have an objective coordinating center and that the investigators jointly develop a written governance document to enable collaboration and preserve collegiality among participating investigators.La ejecución de estudios multicéntricos requiere el establecimiento de procedimientos uniformes, control de calidad, asegurar estandarización, y la colaboración entre las instituciones participantes. Este trabajo describe la estructura y la dinámica de los estudios multicéntricos internacionales, enfocando los aspectos de administración y reglamentación. Se describe la estructura organizativa de un estudio multicéntrico, así como los roles de los integrantes de un sistema de supervisión y coordinación. Se presentan los elementos de un documento de reglamentación y se describen algunas guías y políticas para una colaboración eficaz. La experiencia del estudio internacional colaborativo World Studies of Abuse in the Family Environment (WorldSAFE se utiliza como ejemplo de la aplicación de estas normas. Un centro de coordinación estadística, así como un documento de auto-reglamentación son

Study on de novo collagen biosynthesis and degradation markers of bone

International Nuclear Information System (INIS)

Hanna, L.S.; Matta, T.F.; Ibrahim, I.; Meky, N.H.

2003-01-01

This investigation was carried out to study the performance of de novo biochemical markers of serum pro collagen type-1 amino terminal extension (PINP), as a marker of collagen biosynthesis, and urinary collagen crosslink free deoxypyridinoline (DPD) as a marker of collagen degradation. Moreover, urinary calcium C Ca) and inorganic phosphorus (P), as markers of bone demineralization, in addition to urinary creatinine (Cr), to reflect status of renal function, were also studied in order to assess the activity of bone turnover in osteoporotic (OST), postmenopausal (POST), peri menopausal(PERI), premenopausal (PRE) women and also in young adult (YON) ones. The obtained results showed that urinary creatinine levels were within the normal ranges in all women even in the elderly osteoporotic and postmenopausal women. Serum PINP did not reflect osteoblastic activity. Urinary DPD proved to be a good marker in monitoring the postmenopausal bone resorption and urinary Ca was a reliable marker for bone loss in osteoporosis and bone turnover in the postmenopausal status

Surgical site infections in Italian Hospitals: a prospective multicenter study

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Ippolito Giuseppe

2008-03-01

Full Text Available Abstract Background Surgical site infections (SSI remain a major clinical problem in terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis occur in the postdischarge period. However, literature provides little information on risk factors associated to in-hospital and postdischarge SSI occurrence. A national prospective multicenter study was conducted with the aim of assessing the incidence of both in-hospital and postdisharge SSI, and the associated risk factors. Methods In 2002, a one-month, prospective national multicenter surveillance study was conducted in General and Gynecological units of 48 Italian hospitals. Case ascertainment of SSI was carried out using standardized surveillance methodology. To assess potential risk factors for SSI we used a conditional logistic regression model. We also reported the odds ratios of in-hospital and postdischarge SSI. Results SSI occurred in 241 (5.2% of 4,665 patients, of which 148 (61.4% during in-hospital, and 93 (38.6% during postdischarge period. Of 93 postdischarge SSI, sixty-two (66.7% and 31 (33.3% were detected through telephone interview and questionnaire survey, respectively. Higher SSI incidence rates were observed in colon surgery (18.9%, gastric surgery (13.6%, and appendectomy (8.6%. If considering risk factors for SSI, at multivariate analysis we found that emergency interventions, NNIS risk score, pre-operative hospital stay, and use of drains were significantly associated with SSI occurrence. Moreover, risk factors for total SSI were also associated to in-hospital SSI. Additionally, only NNIS, pre-operative hospital stay, use of drains, and antibiotic prophylaxis were associated with postdischarge SSI. Conclusion Our study provided information on risk factors for SSI in a large population in general surgery setting in Italy. Standardized postdischarge surveillance detected 38.6% of all SSI. We also compared risk factors for in-hospital and postdischarge SSI

Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study

NARCIS (Netherlands)

Blanken, M.O.; Koffijberg, H.; Nibbelke, E.E.; Rovers, M.M.; Bont, L.; Liem, K.D.; et al.,

2013-01-01

OBJECTIVES: This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33-35 weeks gestational age (WGA). STUDY DESIGN: The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were

Language and national identity in Novo Cinema Galego

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Brais ROMERO SUÁREZ

2015-12-01

Full Text Available The talk of town since its inception in 2010, the Cinema Novo Galego has been successful in all competitions and festivals that has been present. From the FIPRESCI prize in Cannes to the Best Emerging Director at Locarno, this new wave of cinema places Galicia in the world film stage. But does Novo Cinema Galego an accurate representation of Galicia? What's the role of Galicia in this movement?

De novo synthesis of adenine nucleotides in different skeletal muscle fiber types

International Nuclear Information System (INIS)

Tullson, P.C.; John-Alder, H.B.; Hood, D.A.; Terjung, R.L.

1988-01-01

Management of adenine nucleotide catabolism differs among skeletal muscle fiber types. This study evaluated whether there are corresponding differences in the rates of de novo synthesis of adenine nucleotide among fiber type sections of skeletal muscle using an isolated perfused rat hindquarter preparation. Label incorporation into adenine nucleotides from the [1-14C]glycine precursor was determined and used to calculate synthesis rates based on the intracellular glycine specific radioactivity. Results show that intracellular glycine is closely related to the direct precursor pool. Rates of de novo synthesis were highest in fast-twitch red muscle (57.0 +/- 4.0, 58.2 +/- 4.4 nmol.h-1.g-1; deep red gastrocnemius and vastus lateralis), relatively high in slow-twitch red muscle (47.0 +/- 3.1; soleus), and low in fast-twitch white muscle (26.1 +/- 2.0 and 21.6 +/- 2.3; superficial white gastrocnemius and vastus lateralis). Rates for four mixed muscles were intermediate, ranging between 32.3 and 37.3. Specific de novo synthesis rates exhibited a strong correlation (r = 0.986) with muscle section citrate synthase activity. Turnover rates (de novo synthesis rate/adenine nucleotide pool size) were highest in high oxidative muscle (0.82-1.06%/h), lowest in low oxidative muscle (0.30-0.35%/h), and intermediate in mixed muscle (0.44-0.55%/h). Our results demonstrate that differences in adenine nucleotide management among fiber types extends to the process of de novo adenine nucleotide synthesis

On the Origin of De Novo Genes in Arabidopsis thaliana Populations.

Science.gov (United States)

Li, Zi-Wen; Chen, Xi; Wu, Qiong; Hagmann, Jörg; Han, Ting-Shen; Zou, Yu-Pan; Ge, Song; Guo, Ya-Long

2016-08-03

De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

De Novo Discovery of Structured ncRNA Motifs in Genomic Sequences

DEFF Research Database (Denmark)

Ruzzo, Walter L; Gorodkin, Jan

2014-01-01

De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphas...... on an approach based on the CMfinder CMfinder program as a case study. Applications to genomic screens for novel de novo structured ncRNA ncRNA s, including structured RNA elements in untranslated portions of protein-coding genes, are presented.......De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphasis...

Extreme-Scale De Novo Genome Assembly

Energy Technology Data Exchange (ETDEWEB)

Georganas, Evangelos [Intel Corporation, Santa Clara, CA (United States); Hofmeyr, Steven [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Egan, Rob [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Buluc, Aydin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Rokhsar, Daniel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Yelick, Katherine [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.

2017-09-26

De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and the large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.

Effectiveness and predictors of success of noninvasive ventilation during H1N1 pandemics: a multicenter study.

Science.gov (United States)

Nicolini, A; Tonveronachi, E; Navalesi, P; Antonelli, M; Valentini, I; Melotti, R M; Pigna, A; Carrassi, A; Righini, P; Ferrari Bravo, M; Pelosi, P; Nicoli, F; Cosentini, R; Vaschetto, R; Faenza, S; Nava, S

2012-12-01

The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure. In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO229 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI. The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Statistics of the Iomazenil-multicenter study

International Nuclear Information System (INIS)

Hasler, P.H.; Beer-Wohlfahrt, H.; Schubiger, P.A.

1990-01-01

The 123 I-Ro 16-0154 (= Iomazenil) has been shown as a very potent benzodiazepine antagonist by Beer et al. (1990). In this study the in vitro and in vivo characteristics have been described. The preliminary clinical results revealed clearly images of the benzodiazepine receptor density in the brain. Also storage defects due to pathological CBF and changed receptor density were detected. The Iomazenil showed potential usefulness and therefore extended clinical tests in a multicenter study have been performed. The goals were twofold, first to define the normal benzodiazepine receptor distribution in a healthy human brain and second to investigate the possible diagnostic usefulness of Iomazenil in the case of partial epilepsy. Furthermore, on a few normal volunteers the pharmacokinetics should be determined and some patients with other dieseases (e.g. Alzheimer) would be screened. Some preliminary clinical results have already been published. Hoell et al. (1989) compared the biodistribution of Iomazenil in normal humans with the animal data published (Beer et al., 1990). They concluded that the distribution was similar. The radioactivity concentration in the plasma was virtually cleared after 15 min., cerebral uptake reached a maximum of 10-15 min p.i. and remained stable for about 20 min. Bangerl et al. (1990) found a reduction of benzodiazepine receptors in patients with Lennox-Gaustaut-syndrome. Bartenstein et al. (1989) compared early (30 min.) and late (2h) SPECT-images. They found that early images showed flow-phenomena and receptor binding, whereas late one corresponded clearly to receptor binding. Their findings confirm the results published by Beer et al. (1990). In this work the patient data of all participating clinical centers are evaluated and discussed. (author) 3 figs., 7 tabs., 5 refs

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

Science.gov (United States)

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

High frequencies of de novo CNVs in bipolar disorder and schizophrenia.

LENUS (Irish Health Repository)

Malhotra, Dheeraj

2011-12-22

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

Accuracy evaluation of five blood glucose monitoring systems obtained from the pharmacy: a European multicenter study with 453 subjects

NARCIS (Netherlands)

Tack, C.J.; Pohlmeier, H.; Behnke, T.; Schmid, V.; Grenningloh, M.; Forst, T.; Pfutzner, A.

2012-01-01

BACKGROUND: This multicenter study was conducted to evaluate the performance of five recently introduced blood glucose (BG) monitoring (BGM) devices under daily routine conditions in comparison with the YSI (Yellow Springs, OH) 2300 Stat Plus glucose analyzer. METHODS: Five hundred one diabetes

Identification of a novel Plasmopara halstedii elicitor protein combining de novo peptide sequencing algorithms and RACE-PCR

Directory of Open Access Journals (Sweden)

Madlung Johannes

2010-05-01

Full Text Available Abstract Background Often high-quality MS/MS spectra of tryptic peptides do not match to any database entry because of only partially sequenced genomes and therefore, protein identification requires de novo peptide sequencing. To achieve protein identification of the economically important but still unsequenced plant pathogenic oomycete Plasmopara halstedii, we first evaluated the performance of three different de novo peptide sequencing algorithms applied to a protein digests of standard proteins using a quadrupole TOF (QStar Pulsar i. Results The performance order of the algorithms was PEAKS online > PepNovo > CompNovo. In summary, PEAKS online correctly predicted 45% of measured peptides for a protein test data set. All three de novo peptide sequencing algorithms were used to identify MS/MS spectra of tryptic peptides of an unknown 57 kDa protein of P. halstedii. We found ten de novo sequenced peptides that showed homology to a Phytophthora infestans protein, a closely related organism of P. halstedii. Employing a second complementary approach, verification of peptide prediction and protein identification was performed by creation of degenerate primers for RACE-PCR and led to an ORF of 1,589 bp for a hypothetical phosphoenolpyruvate carboxykinase. Conclusions Our study demonstrated that identification of proteins within minute amounts of sample material improved significantly by combining sensitive LC-MS methods with different de novo peptide sequencing algorithms. In addition, this is the first study that verified protein prediction from MS data by also employing a second complementary approach, in which RACE-PCR led to identification of a novel elicitor protein in P. halstedii.

Illumina-based de novo transcriptome sequencing and analysis

Indian Academy of Sciences (India)

In the present study, we used Illumina HiSeq technology to perform de novo assembly of heart and musk gland transcriptomes from the Chinese forest musk deer. A total of 239,383 transcripts and 176,450 unigenes were obtained, of which 37,329 unigenes were matched to known sequences in the NCBI nonredundant ...

A multicenter prospective study of patients undergoing open ventral hernia repair with intraperitoneal positioning using the monofilament polyester composite ventral patch

DEFF Research Database (Denmark)

Berrevoet, Frederik; Doerhoff, Carl; Muysoms, Filip

2017-01-01

PURPOSE: This study assessed the recurrence rate and other safety and efficacy parameters following ventral hernia repair with a polyester composite prosthesis (Parietex™ Composite Ventral Patch [PCO-VP]). PATIENTS AND METHODS: A single-arm, multicenter prospective study of 126 patients undergoing...

De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

Directory of Open Access Journals (Sweden)

Veronique Hamel

2017-01-01

Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

Science.gov (United States)

Kloimstein, Herwig; Likar, Rudolf; Kern, Michael; Neuhold, Josef; Cada, Miroslav; Loinig, Nadja; Ilias, Wilfried; Freundl, Brigitta; Binder, Heinrich; Wolf, Andreas; Dorn, Christian; Mozes-Balla, Eva Maria; Stein, Rolf; Lappe, Ivo; Sator-Katzenschlager, Sabine

2014-02-01

The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal. © 2013 International Neuromodulation Society.

Automated de novo phasing and model building of coiled-coil proteins.

Science.gov (United States)

Rämisch, Sebastian; Lizatović, Robert; André, Ingemar

2015-03-01

Models generated by de novo structure prediction can be very useful starting points for molecular replacement for systems where suitable structural homologues cannot be readily identified. Protein-protein complexes and de novo-designed proteins are examples of systems that can be challenging to phase. In this study, the potential of de novo models of protein complexes for use as starting points for molecular replacement is investigated. The approach is demonstrated using homomeric coiled-coil proteins, which are excellent model systems for oligomeric systems. Despite the stereotypical fold of coiled coils, initial phase estimation can be difficult and many structures have to be solved with experimental phasing. A method was developed for automatic structure determination of homomeric coiled coils from X-ray diffraction data. In a benchmark set of 24 coiled coils, ranging from dimers to pentamers with resolutions down to 2.5 Å, 22 systems were automatically solved, 11 of which had previously been solved by experimental phasing. The generated models contained 71-103% of the residues present in the deposited structures, had the correct sequence and had free R values that deviated on average by 0.01 from those of the respective reference structures. The electron-density maps were of sufficient quality that only minor manual editing was necessary to produce final structures. The method, named CCsolve, combines methods for de novo structure prediction, initial phase estimation and automated model building into one pipeline. CCsolve is robust against errors in the initial models and can readily be modified to make use of alternative crystallographic software. The results demonstrate the feasibility of de novo phasing of protein-protein complexes, an approach that could also be employed for other small systems beyond coiled coils.

De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

Science.gov (United States)

Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

2017-09-15

The thyroid gland secretes primarily tetraiodothyronine (T 4 ), and some triiodothyronine (T 3 ). Under normal physiological circumstances, only one-fifth of circulating T 3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T 3 toxicosis. Thyroidal T 4 production results from iodination of thyroglobulin (TG) at residues Tyr 5 and Tyr 130 , whereas thyroidal T 3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T 3 is formed de novo independently of deiodination from T 4 We found that upon iodination in vitro , de novo T 3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T 3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T 3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T 3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T 3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T 3 formation, contributing to the relative T 3 toxicosis of Graves' disease.

De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

Directory of Open Access Journals (Sweden)

Kanodia K

2008-01-01

Full Text Available Collapsing glomerulopathy (CG, characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.

Engineering and introduction of de novo disulphide bridges in ...

Indian Academy of Sciences (India)

The engineeringof de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rationalmethod of protein engineering. In this study, Disulphide by Design software, homology modelling and moleculardynamics simulations were used to select appropriate amino acid pairs for ...

Purine biosynthesis de novo by lymphocytes in gout

International Nuclear Information System (INIS)

Kamoun, P.; Chanard, J.; Brami, M.; Funck-Brentano, J.L.

1978-01-01

A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [ 14 C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. Synthesis of 14 C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values contained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [ 14 C]glycine incorporation into urinary uric acid. (author)

Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: The RESOLVE study

NARCIS (Netherlands)

Jeremias, Allen; Maehara, Akiko; Généreux, Philippe; Asrress, Kaleab N.; Berry, Colin; Bruyne, de B. (Bernard); Davies, Justin E.; Escaned, Javier; Fearon, W.F. (William); Gould, K. Lance; Johnson, Nils P.; Kirtane, Ajay J.; Koo, Bon Kwon; Marques, Koen M.; Nijjer, Sukhjinder; Oldroyd, K.G. (Keith); Petraco, Ricardo; Piek, Jan J.; Pijls, Nico H.; Redwood, Simon; Siebes, M.; Spaan, J.A.E.; van 't Veer, Marcel; Mintz, Gary S.; Stone, Gregg W.

2014-01-01

Objectives This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study.

De novo giant A2 aneurysm following anterior communicating artery occlusion.

Science.gov (United States)

Ibrahim, Tarik F; Hafez, Ahmad; Andrade-Barazarte, Hugo; Raj, Rahul; Niemela, Mika; Lehto, Hanna; Numminen, Jussi; Jarvelainen, Juha; Hernesniemi, Juha

2015-01-01

De novo intracranial aneurysms are reported to occur with varying incidence after intracranial aneurysm treatment. They are purported to be observed, however, with increased incidence after Hunterian ligation; particularly in cases of carotid artery occlusion for giant or complex aneurysms deemed unclippable. We report a case of right-sided de novo giant A2 aneurysm 6 years after an anterior communicating artery (ACoA) aneurysm clipping. We believe this de novo aneurysm developed in part due to patient-specific risk factors but also a significant change in cerebral hemodynamics. The ACoA became occluded after surgery that likely altered the cerebral hemodynamics and contributed to the de novo aneurysm. We believe this to be the first reported case of a giant de novo aneurysm in this location. Following parent vessel occlusion (mostly of the carotid artery), there are no reports of any de novo aneurysms in the pericallosal arteries let alone a giant one. The patient had a dominant right A1 and the sudden increase in A2 blood flow likely resulted in increased wall shear stress, particularly in the medial wall of the A2 where the aneurysm occurred 2 mm distal to the A1-2 junction. ACoA preservation is a key element of aneurysm surgery in this location. Suspected occlusion of this vessel may warrant closer radiographic follow-up in patients with other risk factors for aneurysm development.

The Effectiveness of Silodosin for Nocturnal Polyuria in Elderly Men With Benign Prostatic Hyperplasia: A Multicenter Study

OpenAIRE

Kim, Young Won; Park, Jinsung; Chung, Hong; Kim, Hong-Wook; Kim, Hyung Joon; Jung, Jae Hung; Kim, Won Tae

2015-01-01

Purpose: To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. Methods: This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to...

Photoreactivation of conversion and de novo suppressor mutation in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Bockrath, R C; Plamer, J E [Indiana Univ., Indianapolis (USA). Dept. of Microbiology

1977-04-01

Studies of mutagenesis and photoreactivation in various E.coli strains have shown that conversion mutation of a mutant containing an amber suppressor to one containing an ochre suppressor is sensitive to photoreactivation. Direct photoreactivation by photoreactivating light (PRL) after uv mutagenesis reduced mutation frequencies by a factor of about 2 for each minute of exposure during the first 5 to 8 min of exposure for cells with normal repair capacity. Conversion and potential de novo suppressor mutations were about equally sensitive. For conversion, the sensitivities to PRL were identical in the repair-normal and excisions-repair-deficient strains. For de novo suppressor mutation, the rate of mutation frequency reduction by PRL in the repair-deficient strain was about one-half that in the other strains. The results suggest that ultraviolet radiation produces both de novo suppressor mutation and conversion at the sup(E,B) locus by photoreversible pyrimidine dimers in the DNA. The causative dimers could be Thy()Cyt dimers in the transcribed strand or the non-transcribed strand, respectively.

[Motivations for a consultation before adoption: A multicenter study].

Science.gov (United States)

Thieblemont, M; Francois, P; Poirier, V; Bosdure, E; Munck, M-R; Borsa-Dorion, A; Hazart, I; Moukagni-Pelzer, M; Brunel, D; Peyron, F; de Monleon, J-V

2016-01-01

While the number of international adoptions in France is decreasing, adopted children are older and in poorer health than they used to be. This phenomenon has resulted in an increase in the demand for preadoption consultations over the past several years. This study analyses the reasons for these consultations. Prospective multicenter study conducted from 1 January to 31 December 2013. Ten centers contributed to the study, i.e., 196 preadoption consultations. Seeking medical advice was the reason for 88% of the consultations, whether the advice was based on the study of an identified child's medical file (32%) or a country's healthcare characteristics, whether the country was identified (34%) or not (23%). In 6% of cases, the motive for preadoption consultations was social and familial, and in the last 5% it was to obtain general information about adoption and its procedures. In more than 40% of the cases, whether the child or the country identified, Russia is the subject of the consultation because of the complexity of the files and because of the dreaded but rarely mentioned fetal alcohol syndrome. The deterioration of adopted children's health is an additional worry for future adoption applicants. To provide them with the best information possible without making choices for them, specialists should have substantial experience in adoption before going into these preadoption consultations. Copyright © 2015. Published by Elsevier SAS.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

DEFF Research Database (Denmark)

Connolly, S. J.; Wallentin, L.; Ezekowitz, M. D.

2013-01-01

. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY...

Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly.

Science.gov (United States)

Fritz-Laylin, Lillian K; Levy, Yaron Y; Levitan, Edward; Chen, Sean; Cande, W Zacheus; Lai, Elaine Y; Fulton, Chandler

2016-03-01

Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. © 2016 Wiley Periodicals, Inc.

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

DEFF Research Database (Denmark)

Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

2010-01-01

This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

Toward Developing a Specific Outcome Instrument for Spine Trauma : An Empirical Cross-sectional Multicenter ICF-Based Study by AOSpine Knowledge Forum Trauma

NARCIS (Netherlands)

Oner, F. Cumhur; Sadiqi, Said; Lehr, A. Mechteld; Aarabi, Bizhan; Dunn, Robert N.; Dvorak, Marcel F.; Fehlings, Michael G.; Kandziora, Frank; Post, Marcel W.; Rajasekaran, S.; Vialle, Luiz; Vaccaro, Alexander R.

2015-01-01

Study Design. Empirical cross-sectional multicenter study. Objective. To identify the most commonly experienced problems by patients with traumatic spinal column injuries, excluding patients with complete paralysis. Summary of Background Data. There is no disease or condition-specific outcome

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan

International Nuclear Information System (INIS)

Nakajima, Kenichi; Tamaki, Nagara; Kuwabara, Yoichi; Kawano, Masaya; Matsunari, Ichiro; Taki, Junichi; Nishimura, Shigeyuki; Yamashina, Akira; Ishida, Yoshio; Tomoike, Hitonobu

2008-01-01

Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using 99m Tc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 ± 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 ± 17% and 55 ± 18%, p 99m Tc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study. (orig.)

De Novo Glutamine Synthesis

Science.gov (United States)

He, Qiao; Shi, Xinchong; Zhang, Linqi; Yi, Chang; Zhang, Xuezhen

2016-01-01

Purpose: The aim of this study was to investigate the role of de novo glutamine (Gln) synthesis in the proliferation of C6 glioma cells and its detection with 13N-ammonia. Methods: Chronic Gln-deprived C6 glioma (0.06C6) cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS) inhibitor. 13N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0.06C6 xenografts by micro–positron emission tomography (PET) scanning. The expression of GS in C6 cells and xenografts was assessed by Western blotting and immunohistochemistry, respectively. Results: The Gln-deprived C6 cells showed decreased proliferation ability but had a significant increase in GS expression. Furthermore, we found that low concentration of ammonia was sufficient to maintain the proliferation of Gln-deprived C6 cells, and 13N-ammonia uptake in C6 cells showed Gln-dependent decrease, whereas inhibition of GS markedly reduced the proliferation of C6 cells as well as the uptake of 13N-ammoina. Additionally, microPET/computed tomography exhibited that subcutaneous 0.06C6 xenografts had higher 13N-ammonia uptake and GS expression in contrast to C6 xenografts. Conclusion: De novo Gln synthesis through ammonia–glutamate reaction plays an important role in the proliferation of C6 cells. 13N-ammonia can be a potential metabolic PET tracer for Gln-dependent tumors. PMID:27118759

Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study

NARCIS (Netherlands)

Jeremias, Allen; Maehara, Akiko; Généreux, Philippe; Asrress, Kaleab N.; Berry, Colin; de Bruyne, Bernard; Davies, Justin E.; Escaned, Javier; Fearon, William F.; Gould, K. Lance; Johnson, Nils P.; Kirtane, Ajay J.; Koo, Bon-Kwon; Marques, Koen M.; Nijjer, Sukhjinder; Oldroyd, Keith G.; Petraco, Ricardo; Piek, Jan J.; Pijls, Nico H.; Redwood, Simon; Siebes, Maria; Spaan, Jos A. E.; van 't Veer, Marcel; Mintz, Gary S.; Stone, Gregg W.

2014-01-01

This study sought to examine the diagnostic accuracy of the instantaneous wave-free ratio (iFR) and resting distal coronary artery pressure/aortic pressure (Pd/Pa) with respect to hyperemic fractional flow reserve (FFR) in a core laboratory-based multicenter collaborative study. FFR is an index of

De novo assembly of plant body plan: a step ahead of Deadpool.

Science.gov (United States)

Kareem, Abdul; Radhakrishnan, Dhanya; Sondhi, Yash; Aiyaz, Mohammed; Roy, Merin V; Sugimoto, Kaoru; Prasad, Kalika

2016-08-01

While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom.

Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study.

Science.gov (United States)

Li, An; Li, Wenxiong; Hao, Fengtong; Wang, Haishi

2016-01-01

To evaluate the efficacy of conservative treatment vs. hemoperfusion (HP) vs. HP + continuous veno-venous hemofiltration (CVVH) for acute Paraquat (PQ) poisoning. This was a multicenter retrospective study of patients with PQ poisoning between January 2013 and June 2014. Clinical data and PQ serum levels were collected at baseline and after 24, 48, and 72 h of treatment. Seventy-five, 65, and 43 underwent conservative treatment only (conservative treatment group), conservative treatment + HP (HP group), and conservative treatment + HP + CVVH (HP + CVVH group), respectively. PQ serum levels decreased in all groups after 72 h of treatment (p treatment group. More importantly, PQ blood levels were significantly lower in the HP + CVVH group compared with the HP group at 24 h (p treatment group (p poisoning could decrease PQ blood levels, alleviate organ damage, and increase survival. © 2016 S. Karger AG, Basel.

Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

Science.gov (United States)

Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

2017-03-22

The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Accuracy of cotinine serum test to detect the smoking habit and its association with periodontal disease in a multicenter study.

Science.gov (United States)

Duque, A; Martínez, P-J; Giraldo, A; Gualtero, D-F; Ardila, C-M; Contreras, A; Duarte, S; Lafaurie, G-I

2017-07-01

The validity of the surveys on self-reported smoking status is often questioned because smokers underestimate cigarette use and deny the habit. It has been suggested that self-report should be accompanied by cotinine test. This report evaluates the usefulness of serum cotinine test to assess the association between smoking and periodontal status in a study with a large sample population to be used in studies with other serum markers in epidemiologic and periodontal medicine researches. 578 patients who were part of a multicenter study on blood biomarkers were evaluated about smoking and its relation to periodontal disease. Severity of periodontal disease was determinate using clinical attachment loss (CAL). Smoking was assessed by a questionnaire and a blood sample drawn for serum cotinine determination. The optimal cut-off point for serum cotinine was 10 ng/ml. Serum cotinine showed greater association with severity of CAL than self-report for mild-moderate CAL [OR 2.03 (CI95% 1.16-3.53) vs. OR 1.08 (CI95% 0.62-1.87) ] advanced periodontitis [OR 2.36 (CI95% 1.30- 4.31) vs. OR 2.06 (CI95% 0.97-4.38) ] and extension of CAL > 3 mm [ OR 1.78 (CI95% 1.16-1.71) vs. 1.37 (CI95% 0.89-2.11)]. When the two tests were evaluated together were not shown to be better than serum cotinine test. Self-reported smoking and serum cotinine test ≥ 10ng/ml are accurate ,complementary and more reliable methods to assess the patient's smoking status and could be used in studies evaluating serum samples in large population and multicenter studies. The serum cotinine level is more reliable to make associations with the patient's periodontal status than self-report questionnaire and could be used in multicenter and periodontal medicine studies.

Effect of Metoprolol Versus Carvedilol on Outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy)

DEFF Research Database (Denmark)

Ruwald, Martin H; Ruwald, Anne-Christine H; Jøns, Christian

2013-01-01

This study sought to compare the effects of metoprolol and carvedilol in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study.......This study sought to compare the effects of metoprolol and carvedilol in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study....

One-year results of a prospective randomized, evaluator-blinded, multicenter study comparing TVT and TVT Secur.

OpenAIRE

Andrada Hamer, Maria; Larsson, Per-Göran; Teleman, Pia; Bergqvist, Christina Eten; Persson, Jan

2012-01-01

INTRODUCTION AND HYPOTHESIS: The aim of this prospective randomized multicenter study was to compare retropubic tension-free vaginal tape (TVT) with TVT Secur in terms of efficacy and safety. METHODS: We set out to enrol 280 stress urinary incontinent (SUI) women with a half-time interim analysis of short-term cure and adverse events. The short-term results have previously been published. Of the133 randomized women, 125 underwent surgery, and 121 (TVT n = 61, TVT Secur n = 60)...

A glance at quality score: implication for de novo transcriptome reconstruction of Illumina reads

Directory of Open Access Journals (Sweden)

Stanley Kimbung Mbandi

2014-02-01

Full Text Available Downstream analyses of short-reads from next-generation sequencing platforms are often preceded by a pre-processing step that removes uncalled and wrongly called bases. Standard approaches rely on their associated base quality scores to retain the read or a portion of it when the score is above a predefined threshold. It is difficult to differentiate sequencing error from biological variation without a reference using quality scores. The effects of quality score based trimming have not been systematically studied in de novo transcriptome assembly. Using RNA-Seq data produced from Illumina, we teased out the effects of quality score base filtering or trimming on de novo transcriptome reconstruction. We showed that assemblies produced from reads subjected to different quality score thresholds contain truncated and missing transfrags when compared to those from untrimmed reads. Our data supports the fact that de novo assembling of untrimmed data is challenging for de Bruijn graph assemblers. However, our results indicates that comparing the assemblies from untrimmed and trimmed read subsets can suggest appropriate filtering parameters and enable selection of the optimum de novo transcriptome assembly in non-model organisms.

A Public Trial De Novo

DEFF Research Database (Denmark)

Vedel, Jane Bjørn; Gad, Christopher

2011-01-01

This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial” w.......” The article ends with a discussion of some implications of the analysis, including that policy making, academic research, and public debates might benefit from more detailed accounts of interests and stakes.......This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial......” where the grant and close(r) intermingling between industry and public research was prosecuted and defended. First, the authors address how the grant was framed in the media. Second, they redescribe the case by introducing new “evidence” that, because of this framing, did not reach “the court...

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

Science.gov (United States)

Dong, Shan; Walker, Michael F.; Carriero, Nicholas J.; DiCola, Michael; Willsey, A. Jeremy; Ye, Adam Y.; Waqar, Zainulabedin; Gonzalez, Luis E.; Overton, John D.; Frahm, Stephanie; Keaney, John F.; Teran, Nicole A.; Dea, Jeanselle; Mandell, Jeffrey D.; Bal, Vanessa Hus; Sullivan, Catherine A.; DiLullo, Nicholas M.; Khalil, Rehab O.; Gockley, Jake; Yuksel, Zafer; Sertel, Sinem M.; Ercan-Sencicek, A. Gulhan; Gupta, Abha R.; Mane, Shrikant M.; Sheldon, Michael; Brooks, Andrew I.; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.; Wei, Liping; Sanders, Stephan J.

2014-01-01

SUMMARY Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single nucleotide variants to autism spectrum disorders (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. Through the application of a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR=1.6; 95%CI=1.0-2.7; p=0.03), are more common in female probands (p=0.02), are enriched among genes encoding FMRP targets (p=6×10−9), and arise predominantly on the paternal chromosome (p<0.001). Based on mutation rates in probands versus unaffected siblings, de novo frameshift indels contribute to risk in approximately 3.0% of individuals with ASD. Finally, through observing clustering of mutations in unrelated probands, we report two novel ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. PMID:25284784

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high...

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

De novo-based transcriptome profiling of male-sterile and fertile watermelon lines.

Science.gov (United States)

Rhee, Sun-Ju; Kwon, Taehyung; Seo, Minseok; Jang, Yoon Jeong; Sim, Tae Yong; Cho, Seoae; Han, Sang-Wook; Lee, Gung Pyo

2017-01-01

The whole-genome sequence of watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai), a valuable horticultural crop worldwide, was released in 2013. Here, we compared a de novo-based approach (DBA) to a reference-based approach (RBA) using RNA-seq data, to aid in efforts to improve the annotation of the watermelon reference genome and to obtain biological insight into male-sterility in watermelon. We applied these techniques to available data from two watermelon lines: the male-sterile line DAH3615-MS and the male-fertile line DAH3615. Using DBA, we newly annotated 855 watermelon transcripts, and found gene functional clusters predicted to be related to stimulus responses, nucleic acid binding, transmembrane transport, homeostasis, and Golgi/vesicles. Among the DBA-annotated transcripts, 138 de novo-exclusive differentially-expressed genes (DEDEGs) related to male sterility were detected. Out of 33 randomly selected newly annotated transcripts and DEDEGs, 32 were validated by RT-qPCR. This study demonstrates the usefulness and reliability of the de novo transcriptome assembly in watermelon, and provides new insights for researchers exploring transcriptional blueprints with regard to the male sterility.

De novo transcriptome assembly of Setatria italica variety Taejin

Directory of Open Access Journals (Sweden)

Yeonhwa Jo

2016-06-01

Full Text Available Foxtail millet (Setaria italica belonging to the family Poaceae is an important millet that is widely cultivated in East Asia. Of the cultivated millets, the foxtail millet has the longest history and is one of the main food crops in South India and China. Moreover, foxtail millet is a model plant system for biofuel generation utilizing the C4 photosynthetic pathway. In this study, we carried out de novo transcriptome assembly for the foxtail millet variety Taejin collected from Korea using next-generation sequencing. We obtained a total of 8.676 GB raw data by paired-end sequencing. The raw data in this study can be available in NCBI SRA database with accession number of SRR3406552. The Trinity program was used to de novo assemble 145,332 transcripts. Using the TransDecoder program, we predicted 82,925 putative proteins. BLASTP was performed against the Swiss-Prot protein sequence database to annotate the functions of identified proteins, resulting in 20,555 potentially novel proteins. Taken together, this study provides transcriptome data for the foxtail millet variety Taejin by RNA-Seq.

De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.

Science.gov (United States)

Eichenberger, Michael; Hansson, Anders; Fischer, David; Dürr, Lara; Naesby, Michael

2018-06-01

Anthocyanins (ACNs) are plant secondary metabolites responsible for most of the red, purple and blue colors of flowers, fruits and vegetables. They are increasingly used in the food and beverage industry as natural alternative to artificial colorants. Production of these compounds by fermentation of microorganisms would provide an attractive alternative. In this study, Saccharomyces cerevisiae was engineered for de novo production of the three basic anthocyanins, as well as the three main trans-flavan-3-ols. Enzymes from different plant sources were screened and efficient variants found for most steps of the biosynthetic pathway. However, the anthocyanidin synthase was identified as a major obstacle to efficient production. In yeast, this enzyme converts the majority of its natural substrates leucoanthocyanidins into the off-pathway flavonols. Nonetheless, de novo biosynthesis of ACNs was shown for the first time in yeast and for the first time in a single microorganism. It provides a framework for optimizing the activity of anthocyanidin synthase and represents an important step towards sustainable industrial production of these highly relevant molecules in yeast.

Web Access to Digitised Content of the Exhibition Novo Mesto 1848-1918 at the Dolenjska Museum, Novo Mesto

Directory of Open Access Journals (Sweden)

Majda Pungerčar

2013-09-01

Full Text Available EXTENDED ABSTRACTFor the first time, the Dolenjska museum Novo mesto provided access to digitised museum resources when they took the decision to enrich the exhibition Novo mesto 1848-1918 by adding digital content. The following goals were identified: the digital content was created at the time of exhibition planning and design, it met the needs of different age groups of visitors, and during the exhibition the content was accessible via touch screen. As such, it also served for educational purposes (content-oriented lectures or problem solving team work. In the course of exhibition digital content was accessible on the museum website http://www.novomesto1848-1918.si. The digital content was divided into the following sections: the web photo gallery, the quiz and the game. The photo gallery was designed in the same way as the exhibition and the print catalogue and extended by the photos of contemporary Novo mesto and accompanied by the music from the orchestron machine. The following themes were outlined: the Austrian Empire, the Krka and Novo mesto, the town and its symbols, images of the town and people, administration and economy, social life and Novo mesto today followed by digitised archive materials and sources from that period such as the Commemorative book of the Uniformed Town Guard, the National Reading Room Guest Book, the Kazina guest book, the album of postcards and the Diploma of Honoured Citizen Josip Gerdešič. The Web application was also a tool for a simple and on line selection of digitised material and the creation of new digital content which proved to be much more convenient for lecturing than Power Point presentations. The quiz consisted of 40 questions relating to the exhibition theme and the catalogue. Each question offered a set of three answers only one of them being correct and illustrated by photography. The application auto selected ten questions and valued the answers immediately. The quiz could be accessed

Gene expression signatures predict outcome in non-muscle invasive bladder carcinoma - a multi-center validation study

DEFF Research Database (Denmark)

Andersen, Lars Dyrskjøt; Zieger, Karsten; Real, Francisco X.

2007-01-01

and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic....... CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment....

De novo assembly of highly diverse viral populations

Directory of Open Access Journals (Sweden)

Yang Xiao

2012-09-01

Full Text Available Abstract Background Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. Results We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software. Conclusions We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.

Identification of sentinel lymph nodes in vulvar carcinoma patients with the aid of a patent blue V injection: a multicenter study

NARCIS (Netherlands)

Ansink, A. C.; Sie-Go, D. M.; van der Velden, J.; Sijmons, E. A.; de Barros Lopes, A.; Monaghan, J. M.; Kenter, G. G.; Murdoch, J. B.; ten Kate, F. J.; Heintz, A. P.

1999-01-01

BACKGROUND: The aim of this multicenter study was to investigate the feasibility and negative predictive value of sentinel lymph node detection with blue dye in vulvar carcinoma patients. METHODS: In patients with squamous cell carcinoma of the vulva without suspicious groin lymph nodes, patent blue

Generative Recurrent Networks for De Novo Drug Design.

Science.gov (United States)

Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

2018-01-01

Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Prevalence of hospital malnutrition in Latin America: the multicenter ELAN study.

Science.gov (United States)

Correia, M Isabel T D; Campos, Antonio Carlos L

2003-10-01

We determined the nutrition status and prevalence of malnutrition as determined by the Subjective Global Assessment in Latin America, investigated the awareness of the health team with regard to nutrition status, evaluated the use of nutritional therapy, and assessed the governmental policies regulating the practice of nutritional therapy in each country. This cross-sectional, multicenter epidemiologic study enrolled 9348 hospitalized patients older than 18 y in Latin America. Student's t test and chi-square tests were used to analyze univariate analysis and multiple logistic regression analysis, respectively. Malnutrition was present in 50.2% of the patients studied. Severe malnutrition was present in 11.2% of the entire group. Malnutrition correlated with age (>60 y), presence of cancer and infection, and longer length of hospital stay (P policies ruling the practice of nutritional therapy exist only in Brazil and Costa Rica. Hospital malnutrition in Latin America is highly prevalent. Despite this prevalence, physicians' awareness of malnutrition is weak, nutritional therapy is not used routinely, and governmental policies for nutritional therapy are scarce.

Underweight and malnutrition in home care: A multicenter study.

Science.gov (United States)

Lahmann, Nils A; Tannen, Antje; Suhr, Ralf

2016-10-01

This study aimed to provide representative figures about the prevalence of underweight and malnutrition among home care clients, and to determine the associated risk factors and the provided nutritional nursing interventions. In 2012, a multicenter point prevalence study was conducted among 878 randomly selected clients from 100 randomly selected home care services across Germany. Following a standardized study protocol, demographics, nutritional assessments (Body Mass Index, Malnutrition Universal Screening Tool (MUST), Mini nutritional Assessment - short form (MNA-sf), nurses' clinical judgment on nutritional status) and interventions were assessed. Common nutritional risk factors for underweight and malnutrition were analyzed in a logistic regression model. Malnutrition figures varied between 4.8% (MNA-sf) and 6.8% (MUST), underweight between 8.7% (BMI malnutrition assessments (MNA-sf 48.8%, MUST 39.1%) due to a lack of information on many clients' loss of weight within the past 3-6 months. Regular weighing was performed in 33.6-57.3% of all clients, depending on weight and nutritional status. Mental overload (OR 8.1/4.4), needs help with feeding (OR 5.0/2.8) and loss of appetite (OR 3.6/3.9) were highly associated with malnutrition/underweight. Malnutrition and underweight are important issues in home care clients. Regular weighing should be performed in all home care clients so that a potential weight loss can be detected in time. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Whole-Genome de novo Sequencing Of Quail And Grey Partridge

DEFF Research Database (Denmark)

Holm, Lars-Erik; Panitz, Frank; Burt, Dave

2011-01-01

The development in sequencing methods has made it possible to perform whole genome de novo sequencing of species without large commercial interests. Within the EU-financed QUANTOMICS project (KBBE-2A-222664), we have performed de novo sequencing of quail (Coturnix coturnix) and grey partridge...... (Perdix perdix) on a Genome Analyzer GAII (Illumina) using paired-end sequencing. The amount of generated sequences amounts to 8 to 9 Gb for each species. The analysis and assembly of the generated sequences is ongoing. Access to the whole genome sequence from these two species will enable enhanced...... comparative studies towards the chicken genome and will aid in identifying evolutionarily conserved sequences within the Galliformes. The obtained sequences from quail and partridge represent a beginning of generating the whole genome sequence for these species. The continuation of establishing the genome...

Diagnostic imaging and interventional radiology of hepatocellular carcinoma: A multicenter study on 290 cases

International Nuclear Information System (INIS)

Dalla Palma, Ludovico; Puzzi Mucelli, Roberto; Sponza, Massimo; De Santis, Mario; Gandini, Giovanni; Matricardi, Luigi; Rossi, Cristina

1997-01-01

The authors report of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC).The first aim -diagnostic - was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in hepatocellular carcinoma detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning.The second aim - treatment - consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced hepatocellular carcinoma and of intraarterial chemoembolization versus no treatment (NT) in advanced hepatocellular carcinoma. Treatment efficacy was evaluated with the following randomized protocols

Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

Science.gov (United States)

Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

2015-02-01

De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

De novo autoimmune hepatitis after liver transplantation.

Science.gov (United States)

Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

2007-10-01

The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

Arginine de novo and nitric oxide production in disease states

OpenAIRE

Luiking, Yvette C.; Ten Have, Gabriella A. M.; Wolfe, Robert R.; Deutz, Nicolaas E. P.

2012-01-01

Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin ...

Socio-demographic and clinical profiles of paranoid and nonparanoid schizophrenia: a prospective, multicenter study in China.

Science.gov (United States)

Xiang, Yu-Tao; Wang, Chuan-Yue; Chiu, Helen F K; Weng, Yong-Zhen; Bo, Qi-Jing; Chan, Sandra S M; Lee, Edwin H M; Ungvari, Gabor S

2011-07-01

This study aimed to explore the socio-demographic and clinical characteristics of paranoid and nonparanoid subtypes of schizophrenia. In a multicenter, randomized, controlled, longitudinal study, 374 clinically stable schizophrenia patients were interviewed at entry with standardized assessment instruments and followed for 12-26 months. In the multivariate analysis, male sex, married marital status, urban abode, and more frequent relapse over the study period were independently associated with paranoid schizophrenia. The socio-demographic and clinical characteristics of Chinese patients with the paranoid subtype of schizophrenia are different from those of their Caucasian counterparts who are more likely to be women and have a better outcome. © 2010 Wiley Periodicals, Inc.

Multicenter Study of the Clinical Presentation of Staphylococcus lugdunensis Bacteremia in Japan.

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Ainoda, Yusuke; Takeshita, Nozomi; Hase, Ryota; Mikawa, Takahiro; Hosokawa, Naoto; Kawamura, Ichiro; Kurai, Hanako; Abe, Masahiro; Kimura, Muneyoshi; Araoka, Hideki; Fujita, Takahiro; Totsuka, Kyoichi; Mezaki, Kazuhisa; Sekiya, Noritaka; Ohmagari, Norio

2017-07-24

Staphylococcus lugdunensis (SL) is a bacterium with a highly pathogenicity than most other coagulase-negative Staphylococcus spp. (CoNS). In Japan, data on this pathogen are sparse, and the current prevalence of SL bacteremia is unknown. Therefore, we investigated the prevalence of SL in blood culture specimens in a prospective multicenter study across 5 facilities. A total of 3,284 patients had positive blood cultures, and 2,478 patients had bacteremia. Among the patients with bacteremia, 7 patients (0.28%) had SL bacteremia. A total of 281 patients had CoNS bacteremia, with SL accounting for 2.49% of these cases. Of the 7 patients with SL bacteremia, 1 patient (14.3%) had infective endocarditis, and 1 patient (14.3%) died within 30 days. In this study, SL resulted in the development of bacteremia in select patients. Clinicians in Japan should be aware of the prevalence of SL and the complications of SL bacteremia.

Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

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Kyleen Luhrs

2017-01-01

Full Text Available The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62, de novo deletion copy number variations (DEL, n=74, de novo likely gene-disrupting mutations (LGDM, n=267, and children without a known genetic etiology (NON, n=2111. Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

Safety and effectiveness of the Phoenix Atherectomy System in lower extremity arteries: Early and midterm outcomes from the prospective multicenter EASE study.

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Davis, Thomas; Ramaiah, Venkatesh; Niazi, Khusrow; Martin Gissler, Hans; Crabtree, Tami

2017-12-01

Objectives To evaluate the novel Phoenix Atherectomy System as percutaneous treatment of de novo and restenotic infrainguinal arterial lesions. Methods This prospective, multicenter, nonrandomized investigational device exemption trial was conducted across 16 US and German centers between August 2010 and April 2013. Intention-to-treat enrollment was 128 patients (mean age: 71.8 years, 59% male) with 149 lesions (mean length: 34 mm, mean diameter stenosis: 89.5%), and the primary analysis per-protocol population consisted of 105 patients with 123 lesions. The primary efficacy endpoint, technical success, was the achievement of acute debulking with a post-atherectomy residual diameter stenosis ≤50% (before adjunctive therapy). The primary safety endpoint was the major adverse event (MAE) rate through 30 days. Results For the primary analysis per-protocol population, the rate of lesion technical success was 95.1% (117/123), with the lower limit of the 95% CI 90.6%, meeting the prospectively established target performance goal of ≥86%. After post-atherectomy adjunctive therapy, residual stenosis was ≤30% for 99.2% (122/123) of lesions (mean final diameter stenosis 10.5%). Improvement of ≥1 Rutherford class occurred for 74.5% of patients through 30 days and for 80% through six months. MAEs were experienced by 5.7% (6/105) of patients through 30 days (with the upper limit of the 95% CI 11.0%, meeting the target performance goal of Atherectomy System is safe and effective for the debulking of lower-extremity arterial lesions. ClinicalTrials.gov identifier NCT01541774.

NHash: Randomized N-Gram Hashing for Distributed Generation of Validatable Unique Study Identifiers in Multicenter Research.

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Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong

2015-11-10

A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result

Two-year follow-up of an open-label multicenter study of polyacrylamide hydrogel (Bulkamid®) for female stress and stress-predominant mixed incontinence

DEFF Research Database (Denmark)

Toozs-Hobson, Philip; Al-Singary, Waleed; Fynes, Michelle

2012-01-01

Polyacrylamide hydrogel (PAHG, Bulkamid®) is a promising urethral bulking agent. This article presents the 2-year follow-up results of a multicenter study of PAHG injections for treating stress and stress-predominant mixed urinary incontinence....

A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

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Lorf Thomas

2010-04-01

Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

Anatomical and Physiological Changes after Paclitaxel-Coated Balloon for Atherosclerotic De Novo Coronary Lesions: Serial IVUS-VH and FFR Study.

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Soe Hee Ann

Full Text Available To assess the serial changes of de novo coronary lesions treated with paclitaxel-coated balloon (PCB using intravascular ultrasound virtual histology (IVUS-VH and fractional flow reserve (FFR.This prospective observational study enrolled 27 patients with coronary artery disease treated with PCB who underwent coronary angiography, IVUS-VH and FFR before, immediately after intervention and at 9 months. 28 de novo lesions were successfully treated with PCB. Angiographic late luminal loss was 0.02 ± 0.27 mm. Mean vessel and lumen areas showed increase at 9 months (12.0 ± 3.5 mm(2 to 13.2 ± 3.9 mm(2, p <0.001; and 5.4 ± 1.2 mm(2 to 6.5 ± 1.8 mm(2, p <0.001, respectively. Although mean plaque area was unchanged (6.6 ± 2.6 mm2 to 6.6 ± 2.4 mm(2, p = 0.269, percent atheroma volume decreased significantly (53.4 ± 7.9% to 49.5 ± 6.4%, p = 0.002. The proportion of plaque compositions including fibrous, fibrofatty, dense calcium and necrotic core by IVUS-VH was unchanged at 9 months. The FFR of the treated lesion was 0.71 ± 0.13 pre-procedure, 0.87 ± 0.06 post-procedure and 0.84 ± 0.06 at follow-up.De novo coronary lesions treated with PCB showed persistent anatomical and physiological patency with plaque redistribution and vessel remodeling without chronic elastic recoil or plaque compositional change during follow-up.

Efficient assembly of de novo human artificial chromosomes from large genomic loci

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Stromberg Gregory

2005-07-01

Full Text Available Abstract Background Human Artificial Chromosomes (HACs are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning, manipulating and transferring large segments of the genome. However, development of HACs for the transfer of large genomic loci into mammalian cells has been limited by difficulties in manipulating high-molecular weight DNA, as well as by the low overall frequencies of de novo HAC formation. Indeed, to date, only a small number of large (>100 kb genomic loci have been reported to be successfully packaged into de novo HACs. Results We have developed novel methodologies to enable efficient assembly of HAC vectors containing any genomic locus of interest. We report here the creation of a novel, bimolecular system based on bacterial artificial chromosomes (BACs for the construction of HACs incorporating any defined genomic region. We have utilized this vector system to rapidly design, construct and validate multiple de novo HACs containing large (100–200 kb genomic loci including therapeutically significant genes for human growth hormone (HGH, polycystic kidney disease (PKD1 and ß-globin. We report significant differences in the ability of different genomic loci to support de novo HAC formation, suggesting possible effects of cis-acting genomic elements. Finally, as a proof of principle, we have observed sustained ß-globin gene expression from HACs incorporating the entire 200 kb ß-globin genomic locus for over 90 days in the absence of selection. Conclusion Taken together, these results are significant for the development of HAC vector technology, as they enable high-throughput assembly and functional validation of HACs containing any large genomic locus. We have evaluated the impact of different genomic loci on the frequency of HAC formation and identified segments of genomic DNA that appear to facilitate de novo HAC formation. These genomic loci

[In hospital and mid-term outcome of patients with NIR stent implantation: multicenter ESPORT-NIR registry].

Science.gov (United States)

Iñiguez, A; García, E; Seabra, R; Bordes, P; Bethencourt, A; Rigla, J

2001-05-01

Despite improvements in the results and techniques of catheter-based revascularization, few studies have evaluated the clinical results of the application of new stent designs. We describe the in-hospital and mid-term outcome of patients undergoing a stent NIR implantation. At least 1 Stent NIR was implanted in 1.004 patients (1.136 lesions) recruited from 50 centers in an international, multicenter, prospective, registry (Spain and Portugal NIR stent registry). Inclusion criteria were objective coronary ischemia related to a severe de novo lesion or first restenosis in native vessels with a reference diameter >= 2.75 mm. The primary end-point was the incidence of major adverse cardiac events within the first 7 months of follow-up. The mean age of the patients was 60 years and 82% were male. Angioplasty was indicated due to unstable angina in 61% of the cases. Stent implantation was successfully achieved in 99.6%. Clinical success (angiographic success without in-hospital major events) was achieved in 98.6% of patients. The rate of angiographic restenosis (> 50% stenosis narrowing) was 16% (CI 95%; 11.7-21.2). The accumulated major cardiac adverse event rate at seven months of follow-up was 8.7%: death (0.9%), acute myocardial infarction (1.2%) and target lesion revascularization (6.6%). In the wide setting of the population included in the ESPORT-NIR registry, stent NIR implantation was a highly effective therapy with a good mid-term clinical and angiographic outcome.

Integrating a Patient-Controlled Admission Program Into Mental Health Hospital Service: A Multicenter Grounded Theory Study

DEFF Research Database (Denmark)

Ellegaard, Trine; Bliksted, Vibeke Fuglsang; Mehlsen, Mimi Yung

2018-01-01

Patient-controlled admissions (PCAs) enable mental health patients by means of a contract to initiate an admission at a mental health hospital unit without using traditional admission procedures. This study was part of a 3-year Danish multicenter project, and we explored how mental health...... the mental health professionals strived to integrate PCA into clinical practice. The process was motivated by the idea of establishing a partnership with patients and involved two interrelated strategies to manage (a) the patient-related duties and (b) the admission contracts. The professionals moved from...

Intraorganizational Communication and Job Satisfaction Among Flemish Hospital Nurses: An Exploratory Multicenter Study.

Science.gov (United States)

Vermeir, Peter; Downs, Cal; Degroote, Sophie; Vandijck, Dominique; Tobback, Els; Delesie, Liesbeth; Mariman, An; De Veugele, Myriam; Verhaeghe, Rik; Cambré, Bart; Vogelaers, Dirk

2018-01-01

Intraorganizational communication affects job satisfaction and turnover. The goal of this study was to explore relationships between communication and job satisfaction, intention to leave, and burnout among Flemish hospital nurses. A multicenter questionnaire study was conducted in three hospitals using the Communication Satisfaction Questionnaire, the Turnover Intention subscale of the Questionnaire on the Experience and Evaluation of Work, and the Maslach Burnout Inventory. A visual analog scale measured job satisfaction. The mean job satisfaction score was 7.49/10 (±1.43). Almost 7% of nurse participants (93/1,355) reported a high intent to leave, and 2.9% of the respondents (41/1,454) had a score indicative of burnout. All dimensions of communication were associated with job satisfaction. A low score on any dimension of communication satisfaction, except "Relationship With Employees," was associated with higher intent to leave and burnout. Study findings support the need for management interventions to enhance efficient communication and ensure high-quality care and patient safety.

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages.

Science.gov (United States)

Rangel-Salazar, Rubén; Wickström-Lindholm, Marie; Aguilar-Salinas, Carlos A; Alvarado-Caudillo, Yolanda; Døssing, Kristina B V; Esteller, Manel; Labourier, Emmanuel; Lund, Gertrud; Nielsen, Finn C; Rodríguez-Ríos, Dalia; Solís-Martínez, Martha O; Wrobel, Katarzyna; Wrobel, Kazimierz; Zaina, Silvio

2011-11-25

We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

Identification of de novo mutations of Duchénnè/Becker muscular dystrophies in southern Spain.

Science.gov (United States)

Garcia, Susana; de Haro, Tomás; Zafra-Ceres, Mercedes; Poyatos, Antonio; Gomez-Capilla, Jose A; Gomez-Llorente, Carolina

2014-01-01

Duchénnè/Becker muscular dystrophies (DMD/BMD) are X-linked diseases, which are caused by a de novo gene mutation in one-third of affected males. The study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain) and to establish the percentage of affected males in whom a de novo gene mutation was responsible. Multiplex ligation-dependent probe amplification (MLPA) technology was applied to determine the incidence of DMD/BMD in 84 males with suspicion of the disease and 106 female relatives. Dystrophin gene exon deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son pairs studied. MLPA technology is adequate for the molecular diagnosis of DMD/BMD and establishes whether the mother carries the molecular alteration responsible for the disease, a highly relevant issue for genetic counseling.

LAP-BAND for BMI 30-40: 5-year health outcomes from the multicenter pivotal study.

Science.gov (United States)

Dixon, J B; Eaton, L L; Vincent, V; Michaelson, R

2016-02-01

We performed a 5-year multicenter study to evaluate the safety and effectiveness of the LAP-BAND System surgery (LBS) in patients with obesity with a body mass index (BMI) of 30-39.9 kg m(-)(2). This pivotal study was designed to support LBS application to the US Food and Drug Administration for broadening the indications for surgery and the lower BMI indication was approved with 1-year data in 2011, with the intention to complete the 5-year evaluation. To present broad health outcome data including weight change, patient reported outcomes, comorbidity change and complications during the 5-year study. The study was conducted at seven US private practice clinical trial sites. We enrolled 149 BMI 30-39.9 subjects into a 5-year, multicenter, longitudinal, prospective post-approval study. Data for those completing each time point are presented. The predefined target of at least 30% excess weight loss was achieved by more than 76% of subjects by 1-year and at every year thereafter during the 5-year study. Mean percentage weight loss at 5 years was 15.9±12.4%. Sustained weight loss was accompanied by sustained improvement in generic and weight-specific quality of life, symptoms of depression and the prevalence of binge-eating disorder. The number of subjects with normal fasting triglyceride, high-density lipoprotein cholesterol, plasma glucose and HbA1c increased significantly between baseline and 5 years. Fifty-four months after LBS implantation, the rate of device explants without replacement was 5.4%; however, the rate of explants increased to 12.1% by month 60 owing to no cost-elective band removals offered to subjects at study exit. No deaths or unanticipated adverse device effects were reported. The LBS is safe and effective for people with BMI 30-39.9 with demonstrated improvements in weight loss, comorbidities and quality of life, and with a low explant rate through 5 years following treatment.

Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

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Camila de Andrade Brum

2015-04-01

Full Text Available Background: Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. Objective: To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. Methods: This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Results: Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%, which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. Conclusion: It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

Energy Technology Data Exchange (ETDEWEB)

Brum, Camila de Andrade [Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS (Brazil); Stein, Airton Tetelbom [Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS (Brazil); Grupo Hospitalar Conceição (GHC), Porto Alegre, RS (Brazil); Universidade Luterana do Brasil (ULBRA), Porto Alegre, RS (Brazil); Pellanda, Lucia Campos, E-mail: luciapell.pesquisa@cardiologia.org.br [Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS (Brazil)

2015-04-15

Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

International Nuclear Information System (INIS)

Brum, Camila de Andrade; Stein, Airton Tetelbom; Pellanda, Lucia Campos

2015-01-01

Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

Science.gov (United States)

Geer, Eliza B; Shafiq, Ismat; Gordon, Murray B; Bonert, Vivien; Ayala, Alejandro; Swerdloff, Ronald S; Katznelson, Laurence; Lalazar, Yelena; Manuylova, Ekaterina; Pulaski-Liebert, Karen J; Carmichael, John D; Hannoush, Zeina; Surampudi, Vijaya; Broder, Michael S; Cherepanov, Dasha; Eagan, Marianne; Lee, Jackie; Said, Qayyim; Neary, Maureen P; Biller, Beverly M K

2017-08-01

Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

Multi-Center Electronic Structure Calculations for Plasma Equation of State

Energy Technology Data Exchange (ETDEWEB)

Wilson, B G; Johnson, D D; Alam, A

2010-12-14

We report on an approach for computing electronic structure utilizing solid-state multi-center scattering techniques, but generalized to finite temperatures to model plasmas. This approach has the advantage of handling mixtures at a fundamental level without the imposition of ad hoc continuum lowering models, and incorporates bonding and charge exchange, as well as multi-center effects in the calculation of the continuum density of states.

Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions

DEFF Research Database (Denmark)

Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert

2016-01-01

Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used...

A Multicenter Review of Superior Laryngeal Nerve Injury Following Anterior Cervical Spine Surgery.

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Tempel, Zachary J; Smith, Justin S; Shaffrey, Christopher; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel; Kanter, Adam S

2017-04-01

A retrospective multicenter case-series study; case report and review of the literature. The anatomy and function of the superior laryngeal nerve (SLN) are well described; however, the consequences of SLN injury remain variable and poorly defined. The prevalence of SLN injury as a consequence of cervical spine surgery is difficult to discern as its clinical manifestations are often inconstant and frequently of a subclinical degree. A multicenter study was performed to better delineate the risk factors, prevalence, and outcomes of SLN injury. A retrospective multicenter case-series study involving 21 high-volume surgical centers from the AO Spine North America Clinical Research Network. Medical records for 17 625 patients who received subaxial cervical spine surgery from 2005 to 2011 were reviewed to identify occurrence of 21 predefined treatment complications. Descriptive statistics were provided for baseline patient characteristics. A retrospective review of the neurosurgical literature on SLN injury was also performed. A total of 8887 patients who underwent anterior cervical spine surgery at the participating institutions were screened, and 1 case of SLN palsy was identified. The prevalence ranged from 0% to 1.25% across all centers. The patient identified underwent a C4 corpectomy. The SLN injury was identified after the patient demonstrated difficulty swallowing postoperatively. He underwent placement of a percutaneous gastrostomy tube and his SLN palsy resolved by 6 weeks. This multicenter study demonstrates that identification of SLN injury occurs very infrequently. Symptomatic SLN injury is an exceedingly rare complication of anterior cervical spine surgery. The SLN is particularly vulnerable when exposing the more rostral levels of the cervical spine. Careful dissection and retraction of the longus coli may decrease the risk of SLN injury during anterior cervical surgery.

CT perfusion-guided patient selection for endovascular recanalization in acute ischemic stroke: a multicenter study.

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Turk, Aquilla S; Magarick, Jordan Asher; Frei, Don; Fargen, Kyle Michael; Chaudry, Imran; Holmstedt, Christine A; Nicholas, Joyce; Mocco, J; Turner, Raymond D; Huddle, Daniel; Loy, David; Bellon, Richard; Dooley, Gwendolyn; Adams, Robert; Whaley, Michelle; Fanale, Chris; Jauch, Edward

2013-11-01

The treatment of acute ischemic stroke is traditionally centered on time criteria, although recent evidence suggests that physiologic neuroimaging may be useful. In a multicenter study we evaluated the use of CT perfusion, regardless of time from symptom onset, in patients selected for intra-arterial treatment of ischemic stroke. Three medical centers retrospectively assessed stroke patients with a National Institute of Health Stroke Scale of ≥ 8, regardless of time from symptom onset. CT perfusion maps were qualitatively assessed. Patients with defined salvageable penumbra underwent intra-arterial revascularization of their occlusion. Functional outcome using the modified Rankin Score (mRS) was recorded. Two hundred and forty-seven patients were selected to undergo intra-arterial treatment based on CT perfusion imaging. The median time from symptom onset to procedure was 6 h. Patients were divided into two groups for analysis: ≤ 8 h and >8 h from symptom onset to endovascular procedure. We found no difference in functional outcome between the two groups (42.8% and 41.9% achieved 90-day mRS ≤ 2, respectively (p=1.0), and 54.9% vs 55.4% (p=1.0) achieved 90-day mRS ≤ 3, respectively). Overall, 48 patients (19.4%) had hemorrhages, of which 20 (8.0%) were symptomatic, with no difference between the groups (p=1.0). In a multicenter study, we demonstrated similar rates of good functional outcome and intracranial hemorrhage in patients with ischemic stroke when endovascular treatment was performed based on CT perfusion selection rather than time-guided selection. Our findings suggest that physiologic imaging-guided patient selection rather than time for endovascular reperfusion in ischemic stroke may be effective and safe.

RESULTS OF MULTICENTER STUDY OF PIDOTIMOD FOR THE PROPHYLAXIS OF ACUTE RESPIRATORY INFECTIONS IN FREQUENTLY AILING CHILDREN

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L.S. Namazova-Baranova

2010-01-01

Full Text Available The article describes actual pediatric problem — frequent development of respiratory infections in children. Authors present the results of Russian multicenter study of effectiveness and safety of pidotimod (Imunorix in frequently ailing children. It was shown that treatment with pidotimod during 30 days resulted in decreased rate of acute respiratory infections and their complications including ones with necessity of antibacterial therapy compared to children from control group. The dynamics of immunological rates in blood serum was studied.Key words: frequently ailing children, acute respiratory infections, prophylaxis, pidotimod.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(2:40-44

Modular Engineering Concept at Novo Nordisk Engineering

DEFF Research Database (Denmark)

Moelgaard, Gert; Miller, Thomas Dedenroth

1997-01-01

This report describes the concept of a new engineering method at Novo Nordisk Engineering: Modular Engineering (ME). Three tools are designed to support project phases with different levels of detailing and abstraction. ME supports a standard, cross-functional breakdown of projects that facilitates...

Cervical Spine Injury: A ten‑year multicenter analysis of evolution of ...

African Journals Online (AJOL)

Study Design: Retrospective study. Objective: To describe the evolution of care and risk factors for poor outcome in patients with cervical spine injury (CSI) treated at three centers in southeast Nigeria. Setting: Nigeria, southeast. Materials and Methods: A 10‑year retrospective multicenter analysis of patients with CSI, ...

Wegener's granulomatosis occurring de novo during pregnancy.

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Alfhaily, F; Watts, R; Leather, A

2009-01-01

Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients.

Optimizing de novo common wheat transcriptome assembly using short-read RNA-Seq data

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Duan Jialei

2012-08-01

Full Text Available Abstract Background Rapid advances in next-generation sequencing methods have provided new opportunities for transcriptome sequencing (RNA-Seq. The unprecedented sequencing depth provided by RNA-Seq makes it a powerful and cost-efficient method for transcriptome study, and it has been widely used in model organisms and non-model organisms to identify and quantify RNA. For non-model organisms lacking well-defined genomes, de novo assembly is typically required for downstream RNA-Seq analyses, including SNP discovery and identification of genes differentially expressed by phenotypes. Although RNA-Seq has been successfully used to sequence many non-model organisms, the results of de novo assembly from short reads can still be improved by using recent bioinformatic developments. Results In this study, we used 212.6 million pair-end reads, which accounted for 16.2 Gb, to assemble the hexaploid wheat transcriptome. Two state-of-the-art assemblers, Trinity and Trans-ABySS, which use the single and multiple k-mer methods, respectively, were used, and the whole de novo assembly process was divided into the following four steps: pre-assembly, merging different samples, removal of redundancy and scaffolding. We documented every detail of these steps and how these steps influenced assembly performance to gain insight into transcriptome assembly from short reads. After optimization, the assembled transcripts were comparable to Sanger-derived ESTs in terms of both continuity and accuracy. We also provided considerable new wheat transcript data to the community. Conclusions It is feasible to assemble the hexaploid wheat transcriptome from short reads. Special attention should be paid to dealing with multiple samples to balance the spectrum of expression levels and redundancy. To obtain an accurate overview of RNA profiling, removal of redundancy may be crucial in de novo assembly.

De novo ORFs in Drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences.

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Josephine A Reinhardt

Full Text Available How non-coding DNA gives rise to new protein-coding genes (de novo genes is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution of an open reading frame. In contrast, four other de novo genes evolved a translated open reading frame and transcription within the same evolutionary interval suggesting that nascent open reading frames (proto-ORFs, while not required, can contribute to the emergence of a new de novo gene. However, none of the genes arose from proto-ORFs that existed long before expression evolved. Sequence and structural evolution of de novo genes was rapid compared to nearby genes and the structural complexity of de novo genes steadily increases over evolutionary time. Despite the fact that these genes are transcribed at a higher level in males than females, and are most strongly expressed in testes, RNAi experiments show that most of these genes are essential in both sexes during metamorphosis. This lethality suggests that protein coding de novo genes in Drosophila quickly become functionally important.

Investigation of the current situation of massive blood transfusion in different surgical departments: a large multicenter study in China

OpenAIRE

Sun, Yang; Jin, Zhan-Kui; Xu, Cui-Xiang; Dang, Qian-Li; Zhang, Li-Jie; Chen, Hong-Nan; Song, Yao-Jun; Yang, Jiang-Cun

2015-01-01

Objective: This study aims to learn about the current situation of surgical massive blood transfusion of different surgical departments in China’s Tertiary hospitals, which could provide the basis for the formulation of guidelines on massive blood transfusion. Method: A multicenter retrospective research on the application status of blood constituents during massive blood transfusion was conducted and a comparative analyses of survival and length of hospitalization in patients from different ...

?I have to live like I?m old.? Young adults? perspectives on managing hypertension: a multi-center qualitative study

OpenAIRE

Johnson, Heather M.; Warner, Ryan C.; LaMantia, Jamie N.; Bowers, Barbara J.

2016-01-01

Background In the U.S., young adults (18?39 year-olds) have the lowest hypertension control rates among hypertensive adults. Understanding young adults? unique perceptions about hypertension and perceived barriers to hypertension control is critical to develop effective interventions for this population. This multi-center study explored young adults?: 1) emotions and reactions after a hypertension diagnosis, 2) attitudes about managing hypertension (lifestyle changes, follow-up visits, antihy...

Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

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Rangel-Salazar Rubén

2011-11-01

Full Text Available Abstract Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20 hypermethylation in THP-1 macrophages. Here, we: 1 ask what gene expression changes accompany these epigenetic responses; 2 test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Results Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1 surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2 independent of the Dicer/micro-RNA pathway. Conclusions Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

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Tay, Wei Lin; Loh, Wann Jia; Lee, Lianne Ai Ling; Chng, Chiaw Ling

2017-01-01

We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

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Chen, Yi-Chan; Cheng, Chih-Hsien; Wang, Yu-Chao; Wu, Ting-Jun; Chou, Hong-Shiue; Chan, Kun-Ming; Lee, Wei-Chen; Lee, Chen-Fang; Soong, Ruey Shyang

2016-09-01

Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population.From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports.Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population.Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study

DEFF Research Database (Denmark)

Giovannini, Marc; Thomas, Botelberge; Erwan, Bories

2009-01-01

AIM: To evaluate the ability of endoscopic ultrasound (EUS) elastography to distinguish benign from malignant pancreatic masses and lymph nodes. METHODS: A multicenter study was conducted and included 222 patients who underwent EUS examination with assessment of a pancreatic mass (n = 121) or lymph...... node (n = 101). The classification as benign or malignant, based on the real time elastography pattern, was compared with the classification based on the B-mode EUS images and with the final diagnosis obtained by EUS-guided fine needle aspiration (EUS-FNA) and/or by surgical pathology. An interobserver...... study was performed. RESULTS: The sensitivity and specificity of EUS elastography to differentiate benign from malignant pancreatic lesions are 92.3% and 80.0%, respectively, compared to 92.3% and 68.9%, respectively, for the conventional B-mode images. The sensitivity and specificity of EUS...

Selecting Superior De Novo Transcriptome Assemblies: Lessons Learned by Leveraging the Best Plant Genome.

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Loren A Honaas

Full Text Available Whereas de novo assemblies of RNA-Seq data are being published for a growing number of species across the tree of life, there are currently no broadly accepted methods for evaluating such assemblies. Here we present a detailed comparison of 99 transcriptome assemblies, generated with 6 de novo assemblers including CLC, Trinity, SOAP, Oases, ABySS and NextGENe. Controlled analyses of de novo assemblies for Arabidopsis thaliana and Oryza sativa transcriptomes provide new insights into the strengths and limitations of transcriptome assembly strategies. We find that the leading assemblers generate reassuringly accurate assemblies for the majority of transcripts. At the same time, we find a propensity for assemblers to fail to fully assemble highly expressed genes. Surprisingly, the instance of true chimeric assemblies is very low for all assemblers. Normalized libraries are reduced in highly abundant transcripts, but they also lack 1000s of low abundance transcripts. We conclude that the quality of de novo transcriptome assemblies is best assessed through consideration of a combination of metrics: 1 proportion of reads mapping to an assembly 2 recovery of conserved, widely expressed genes, 3 N50 length statistics, and 4 the total number of unigenes. We provide benchmark Illumina transcriptome data and introduce SCERNA, a broadly applicable modular protocol for de novo assembly improvement. Finally, our de novo assembly of the Arabidopsis leaf transcriptome revealed ~20 putative Arabidopsis genes lacking in the current annotation.

IgM myeloma: A multicenter retrospective study of 134 patients.

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Castillo, Jorge J; Jurczyszyn, Artur; Brozova, Lucie; Crusoe, Edvan; Czepiel, Jacek; Davila, Julio; Dispenzieri, Angela; Eveillard, Marion; Fiala, Mark A; Ghobrial, Irene M; Gozzetti, Alessandro; Gustine, Joshua N; Hajek, Roman; Hungria, Vania; Jarkovsky, Jiri; Jayabalan, David; Laubach, Jacob P; Lewicka, Barbara; Maisnar, Vladimir; Manasanch, Elisabet E; Moreau, Philippe; Morgan, Elizabeth A; Nahi, Hareth; Niesvizky, Ruben; Paba-Prada, Claudia; Pika, Tomas; Pour, Ludek; Reagan, John L; Richardson, Paul G; Shah, Jatin; Spicka, Ivan; Vij, Ravi; Waszczuk-Gajda, Anna; Gertz, Morie A

2017-08-01

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL -1 with 19% of patients presenting with levels >6,000 mg dL -1 . International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t(11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes. © 2017 Wiley Periodicals, Inc.

De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder

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Shan Dong

2014-10-01

Full Text Available Summary: Whole-exome sequencing (WES studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs to autism spectrum disorder (ASD. However, challenges in the reliable detection of de novo insertions and deletions (indels have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals, we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0–2.7; p = 0.03, are more common in female probands (p = 0.02, are enriched among genes encoding FMRP targets (p = 6 × 10−9, and arise predominantly on the paternal chromosome (p < 0.001. On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. : Insertions and deletions (indels have proven especially difficult to detect in exome sequencing data. Dong et al. now identify indels in exome data for 787 autism spectrum disorder (ASD families. They demonstrate association between de novo indels that alter the reading frame and ASD. Furthermore, by observing clustering of indels in unrelated probands, they uncover two additional ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.

Isolated optic nerve gliomas: a multicenter historical cohort study.

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Shofty, Ben; Ben-Sira, Liat; Kesler, Anat; Jallo, George; Groves, Mari L; Iyer, Rajiv R; Lassaletta, Alvaro; Tabori, Uri; Bouffet, Eric; Thomale, Ulrich-Wilhelm; Hernáiz Driever, Pablo; Constantini, Shlomi

2017-12-01

OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors progressed, 23% remained stable, and 18% (all with neurofibromatosis Type 1) displayed some degree of spontaneous regression. Fifty-one percent of the patients presented with visual decline, of whom 90% experienced further deterioration. Nine patients were treated with chemotherapy, 5 of whom improved visually. Ten patients underwent operation, and no local or distal recurrence was noted. CONCLUSIONS Isolated optic nerve gliomas are highly dynamic tumors. Radiological progression and visual deterioration occur in greater percentages than in the general population of patients with OPGs. Response to chemotherapy may be better in this group, and its use should be considered early in the course of the disease.

Prevalence of genital Chlamydia trachomatis infections in Russia: systematic literature review and multicenter study.

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Smelov, Vitaly; Thomas, Pierre; Ouburg, Sander; Morré, Servaas A

2017-09-29

A reliable overview of data on the prevalence of Chlamydia trachomatis (CT) in Russia is lacking and needed. All the available data on CT prevalence were analyzed in a systematic literature review on CT prevalence in Russia, strengthened with data from the multicenter study among 1263 people in the second-largest Russian megalopolis, St. Petersburg, testing for CT DNA in urethral, anal, cervical and prostate samples. A total of 10 articles met the inclusion criteria. The overall average prevalence of genital CT infections in Russian populations ranged from 2.9% to 33%. Risk factors included being symptomatic (P = 0.004; in men P Russia should be considered. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rapid hybrid de novo assembly of a microbial genome using only short reads: Corynebacterium pseudotuberculosis I19 as a case study.

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Cerdeira, Louise Teixeira; Carneiro, Adriana Ribeiro; Ramos, Rommel Thiago Jucá; de Almeida, Sintia Silva; D'Afonseca, Vivian; Schneider, Maria Paula Cruz; Baumbach, Jan; Tauch, Andreas; McCulloch, John Anthony; Azevedo, Vasco Ariston Carvalho; Silva, Artur

2011-08-01

Due to the advent of the so-called Next-Generation Sequencing (NGS) technologies the amount of monetary and temporal resources for whole-genome sequencing has been reduced by several orders of magnitude. Sequence reads can be assembled either by anchoring them directly onto an available reference genome (classical reference assembly), or can be concatenated by overlap (de novo assembly). The latter strategy is preferable because it tends to maintain the architecture of the genome sequence the however, depending on the NGS platform used, the shortness of read lengths cause tremendous problems the in the subsequent genome assembly phase, impeding closing of the entire genome sequence. To address the problem, we developed a multi-pronged hybrid de novo strategy combining De Bruijn graph and Overlap-Layout-Consensus methods, which was used to assemble from short reads the entire genome of Corynebacterium pseudotuberculosis strain I19, a bacterium with immense importance in veterinary medicine that causes Caseous Lymphadenitis in ruminants, principally ovines and caprines. Briefly, contigs were assembled de novo from the short reads and were only oriented using a reference genome by anchoring. Remaining gaps were closed using iterative anchoring of short reads by craning to gap flanks. Finally, we compare the genome sequence assembled using our hybrid strategy to a classical reference assembly using the same data as input and show that with the availability of a reference genome, it pays off to use the hybrid de novo strategy, rather than a classical reference assembly, because more genome sequences are preserved using the former. Copyright © 2011 Elsevier B.V. All rights reserved.

De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

DEFF Research Database (Denmark)

Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín

2011-01-01

Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

Prospective, Multicenter Validation Study of Magnetic Resonance Volumetry for Response Assessment After Preoperative Chemoradiation in Rectal Cancer: Can the Results in the Literature be Reproduced?

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Martens, Milou H., E-mail: mh.martens@hotmail.com [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Heeswijk, Miriam M. van [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Broek, Joris J. van den [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Rao, Sheng-Xiang [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Department of Radiology, Fudan University, Shanghai (China); Vandecaveye, Vincent [Department of Radiology, University Hospital Leuven, Leuven (Belgium); Vliegen, Roy A. [Department of Radiology, Atrium Medical Center, Heerlen (Netherlands); Schreurs, Wilhelmina H. [Department of Surgery, Medical Center Alkmaar, Alkmaar (Netherlands); Beets, Geerard L. [Department of Surgery, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands); Lambregts, Doenja M.J. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); Beets-Tan, Regina G.H. [Department of Radiology, Maastricht University Medical Center, Maastricht (Netherlands); GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht (Netherlands)

2015-12-01

Purpose: To review the available literature on tumor size/volume measurements on magnetic resonance imaging for response assessment after chemoradiotherapy, and validate these cut-offs in an independent multicenter patient cohort. Methods and Materials: The study included 2 parts. (1) Review of the literature: articles were included that assessed the accuracy of tumor size/volume measurements on magnetic resonance imaging for tumor response assessment. Size/volume cut-offs were extracted; (2) Multicenter validation: extracted cut-offs from the literature were tested in a multicenter cohort (n=146). Accuracies were calculated and compared with reported results from the literature. Results: The review included 14 articles, in which 3 different measurement methods were assessed: (1) tumor length; (2) 3-dimensonial tumor size; and (3) whole volume. Study outcomes consisted of (1) complete response (ypT0) versus residual tumor; (2) tumor regression grade 1 to 2 versus 3 to 5; and (3) T-downstaging (ypTmulticenter cohort, best results were obtained for the validation of the whole-volume measurements, in particular for the outcome ypT0 (accuracy 44%-80%), with the optimal cut-offs being 1.6 cm{sup 3} (after chemoradiation therapy) and a volume reduction of Δ80% to 86.6%. Accuracies for whole-volume measurements to assess tumor regression grade 1 to 2 were 52% to 61%, and for T-downstaging 51% to 57%. Overall accuracies for tumor length ranged between 48% and 53% and for 3D size measurement between 52% and 56%. Conclusions: Magnetic resonance volumetry using whole-tumor volume measurements can be helpful in rectal cancer response assessment with selected cut-off values. Measurements of tumor length or 3-dimensional tumor size are not helpful. Magnetic resonance volumetry is mainly accurate to assess a complete tumor response (ypT0) after chemoradiation therapy (accuracies up to 80%).

Validation of standard operating procedures in a multicenter retrospective study to identify -omics biomarkers for chronic low back pain.

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Concetta Dagostino

Full Text Available Chronic low back pain (CLBP is one of the most common medical conditions, ranking as the greatest contributor to global disability and accounting for huge societal costs based on the Global Burden of Disease 2010 study. Large genetic and -omics studies provide a promising avenue for the screening, development and validation of biomarkers useful for personalized diagnosis and treatment (precision medicine. Multicentre studies are needed for such an effort, and a standardized and homogeneous approach is vital for recruitment of large numbers of participants among different centres (clinical and laboratories to obtain robust and reproducible results. To date, no validated standard operating procedures (SOPs for genetic/-omics studies in chronic pain have been developed. In this study, we validated an SOP model that will be used in the multicentre (5 centres retrospective "PainOmics" study, funded by the European Community in the 7th Framework Programme, which aims to develop new biomarkers for CLBP through three different -omics approaches: genomics, glycomics and activomics. The SOPs describe the specific procedures for (1 blood collection, (2 sample processing and storage, (3 shipping details and (4 cross-check testing and validation before assays that all the centres involved in the study have to follow. Multivariate analysis revealed the absolute specificity and homogeneity of the samples collected by the five centres for all genetics, glycomics and activomics analyses. The SOPs used in our multicenter study have been validated. Hence, they could represent an innovative tool for the correct management and collection of reliable samples in other large-omics-based multicenter studies.

Oral cancer in the UAE: a multicenter, retrospective study

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Anis, Raeefa; Gaballah, Kamis

2013-01-01

Aim To determine the prevalence of various malignant oral lesions in the UAE and correlate cases of squamous cell carcinomas with age, gender, site, grade, clinical presentations at the time of diagnosis, and the prevalence of neck metastasis. Materials and methods A multicenter, retrospective study was conducted at four major hospitals in the UAE. The study was based on histopathology reports of biopsies of oral tissues. Results Of the 992 oral biopsy reports retrieved, 147 cases of malignant tumors were found which accounted for 14.9% of the total biopsies. Fifteen different types of malignant lesions were diagnosed, of which oral squamous cell carcinoma (OSCC) was the most prevalent and made up 11.4% of the overall oral biopsies retrieved. The commonest presentation of cancer was ulceration (31.17%), followed by lumps and white lesions. The most common site where the lesions were diagnosed was the tongue (51.9%), followed by the cheeks and lips. OSCC accounted for 77% of all malignancies reported. Neck dissections were conducted in only 20.8% of all OSCC cases diagnosed at Mafraq and Tawam hospitals, of which 43.75% showed evidence of neck metastasis. Conclusion Oral cancer is not an uncommon disease in the UAE. This may mandate more awareness campaigning, including screening procedures for early detection of cancerous lesions and other potentially malignant oral diseases. Elective neck dissections to detect lymph node metastasis should be more routinely performed, in particular for tongue carcinomas because of the early neck involvement potential. PMID:23985381

Interplay between De Novo Biosynthesis and Sequestration of Cyanogenic Glucosides in Arthropods

DEFF Research Database (Denmark)

Fürstenberg-Hägg, Joel

(Zygaenidae, Lepidoptera) both sequester (take up and accumulate) the CNglcs linamarin and lotaustralin from their food plants (Fabacea) and biosynthesize them de novo from valine and isoleucine. The presented research demonstrates that de novo biosynthesis of CNglcs in Z. filipendulae is dependent...

Novo Jornalismo: fronteiras litero-factuais em A sangue Frio e em Radical Chique

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Francisco Aquinei Timóteo Queirós

2012-12-01

Full Text Available A pesquisa busca analisar de que forma fato e ficção se entrecruzam no “movimento” do Novo Jornalismo, a partir das obras A sangue Frio e Radical Chique e o Novo Jornalismo, de Truman Capote e Tom Wolfe, respectivamente. Pretende-se, a partir da investigação do corpus em estudo, revelar os aspectos que aproximam o fato jornalístico, a notícia e a reportagem às técnicas literárias do romance, do conto e da crônica. O estudo investiga o Novo Jornalismo sob o viés de textos centrais das áreas de teoria literária e estudos jornalísticos utilizando autores como Mikhail Bakhtin, Hayden White, Paul Ricoeur, Muniz Sodré; além de referenciar outros escritores que, como Tom Wolfe e Truman Capote, fizeram parte de um grande movimento renovador do jornalismo literário nos anos 1950, 1960 e 1970 chamado, genericamente, de Novo Jornalismo.

Demanda dos principais metais e novos materiais : analise de tendencias

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Wilson Trigueiro de Sousa

1990-01-01

Resumo: Neste trabalho são analisadas algumas tendências na área de novos materiais na tentativa de obter um melhor entendimento das repercussões das atuais inovações tecnológicas para o setor mineral. Inicialmente são revisados os principais estudos sobre as mudanças ocorridas por volta de 1972/74 no comportamento da demanda dos metais mais importantes. Entre as possíveis causas, está o progresso técnico, que tornou possível o surgimento de novos materiais e o aperfeiçoamento de outros em us...

Immobilization of cadmium in soils by UV-mutated Bacillus subtilis 38 bioaugmentation and NovoGro amendment

International Nuclear Information System (INIS)

Jiang Chunxiao; Sun Hongwen; Sun Tieheng; Zhang Qingmin; Zhang Yanfeng

2009-01-01

Immobilization of cadmium (10 mg Cd per kilogram soil) in soil by bioaugmentation of a UV-mutated microorganism, Bacillus subtilis 38 accompanied with amendment of a bio-fertilizer, NovoGro was investigated using extractable cadmium (E-Cd) by DTPA. B. subtilis 38, the mutant with the strongest resistance against Cd, could bioaccumulate Cd four times greater than the original wild type. Single bioaugmentation of B. subtilis 38 (SB treatment) to soil however did not reduce E-Cd significantly, while the amendment of NovoGro (SN treatment) reduced E-Cd remarkably. Simultaneous application of B. subtilis 38 and NovoGro (SNB treatment) exhibited a synergetic effect compared to the single SB and SN treatment. The immobilization effect was significantly affected by temperature, soil moisture, and pH. It seems that the immobilization on Cd reached the maximum when environmental conditions favored the activity of microorganisms. Under the optimum conditions, after 90 days incubation, E-Cd was 3.34, 3.39, 2.25 and 0.87 mg kg -1 in the control soil, SB, SN and SNB soils, respectively. NovoGro not only showed a great capacity for Cd adsorption, but also promoted the growth of B. subtilis 38. This study provides a potential cost-effective technique for in situ remediation of Cd contaminated soils with bioaugmentation.

Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease

DEFF Research Database (Denmark)

Berti, Valentina; Polito, C; Borghammer, Per

2012-01-01

, recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread...... metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev...... normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore...

Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

DEFF Research Database (Denmark)

Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

2017-01-01

or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

Establishment of an Italian chronic migraine database: a multicenter pilot study.

Science.gov (United States)

Barbanti, Piero; Fofi, L; Cevoli, S; Torelli, P; Aurilia, C; Egeo, G; Grazzi, L; D'Amico, D; Manzoni, G C; Cortelli, P; Infarinato, F; Vanacore, N

2018-05-01

To optimize chronic migraine (CM) ascertainment and phenotype definition, provide adequate clinical management and health care procedures, and rationalize economic resources allocation, we performed an exploratory multicenter pilot study aimed at establishing a CM database, the first step for developing a future Italian CM registry. We enrolled 63 consecutive CM patients in four tertiary headache centers screened with face-to-face interviews using an ad hoc dedicated semi-structured questionnaire gathering detailed information on life-style, behavioral and socio-demographic factors, comorbidities, and migraine features before and after chronicization and healthcare resource use. Our pilot study provided useful insights revealing that CM patients (1) presented in most cases symptoms of peripheral trigeminal sensitization, a relatively unexpected feature which could be useful to unravel different CM endophenotypes and to predict trigeminal-targeted treatments' responsiveness; (2) had been frequently admitted to emergency departments; (3) had undergone, sometime repeatedly, unnecessary or inappropriate investigations; (4) got rarely illness benefit exemption or disability allowance only. We deem that the expansion of the database-shortly including many other Italian headache centers-will contribute to more precisely outline CM endophenotypes, hence improving management, treatment, and economic resource allocation, ultimately reducing CM burden on both patients and health system.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

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Yoshioka, Yasuo; Kotsuma, Tadayuki; Komiya, Akira; Kariya, Shinji; Konishi, Koji; Nonomura, Norio; Ogawa, Kazuhiko; Tanaka, Eiichi; Nishimura, Kensaku; Fujiuchi, Yasuyoshi; Kitamura, Hiroshi; Yamagami, Takuji; Yamasaki, Ichiro; Nishimura, Kazuo; Teshima, Teruki; Nakamura, Katsumasa; Itami, Jun

2017-01-01

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy 3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

Nationwide, Multicenter, Retrospective Study on High-Dose-Rate Brachytherapy as Monotherapy for Prostate Cancer

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Yoshioka, Yasuo, E-mail: yoshioka@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Kotsuma, Tadayuki [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Komiya, Akira [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Department of Urology, Chiba University Hospital, Chiba (Japan); Kariya, Shinji [Department of Radiology, Kochi Medical School, Kochi (Japan); Konishi, Koji [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nonomura, Norio [Department of Urology, Osaka University Graduate School of Medicine, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Osaka (Japan); Tanaka, Eiichi [Department of Radiation Oncology, Osaka National Hospital, Osaka (Japan); Nishimura, Kensaku [Department of Urology, Osaka National Hospital, Osaka (Japan); Fujiuchi, Yasuyoshi; Kitamura, Hiroshi [Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Toyama (Japan); Yamagami, Takuji [Department of Radiology, Kochi Medical School, Kochi (Japan); Yamasaki, Ichiro [Department of Urology, Kochi Medical School, Kochi (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Teshima, Teruki [Department of Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Nakamura, Katsumasa [Department of Radiation Oncology, Hamamatsu University School of Medicine, Shizuoka (Japan); Itami, Jun [Department of Radiation Oncology, National Cancer Center Hospital, Tokyo (Japan)

2017-04-01

Purpose: To present, analyze, and discuss results of a nationwide, multicenter, retrospective study on high-dose-rate brachytherapy (HDR-BT) as monotherapy for low-, intermediate-, and high-risk prostate cancer. Methods and Materials: From 1995 through 2013, 524 patients, 73 (14%) with low-risk, 207 (40%) with intermediate-risk, and 244 (47%) with high-risk prostate cancer, were treated with HDR-BT as monotherapy at 5 institutions in Japan. Dose fractionations were 27 Gy/2 fractions for 69 patients (13%), 45.5 Gy/7 fractions for 168 (32%), 49 Gy/7 fractions for 149 (28%), 54 Gy/9 fractions for 130 (25%), and others for 8 (2%). Of these patients, 156 (30%) did not receive androgen deprivation therapy, and 202 patients (39%) did receive androgen deprivation therapy <1 year, 112 (21%) for 1-3 years, and 54 (10%) for >3 years. Median follow-up time was 5.9 years (range, 0.4-18.1 years), with a minimum of 2 years for surviving patients. Results: After 5 years, respective actuarial rates of no biochemical evidence of disease, overall survival, cause-specific survival, and metastasis-free survival for all patients were 92%, 97%, 99%, and 94%. For low/intermediate/high-risk patients, the 5-year no biochemical evidence of disease rates were 95%/94%/89%, the 5-year overall survival rates were 98%/98%/94%, the 5-year cause-specific survival rates were 98%/100%/98%, and the 5-year metastasis-free survival rates were 98%/95%/90%, respectively. The cumulative incidence of late grade 2 to 3 genitourinary toxicity at 5 years was 19%, and that of late grade 3 was 1%. The corresponding incidences of gastrointestinal toxicity were 3% and 0% (0.2%). No grade 4 or 5 of either type of toxicity was detected. Conclusions: The findings of this nationwide, multicenter, retrospective study demonstrate that HDR-BT as monotherapy was safe and effective for all patients with low-, intermediate-, and high-risk prostate cancer.

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy

OpenAIRE

Villanueva, Cristina M.; Gracia-Lavedan, Esther; Bosetti, Cristina; Righi, Elena; Molina, Antonio José; Martín, Vicente; Boldo, Elena; Aragonés, Nuria; Pérez Gómez, Beatriz; Pollán, Marina; Gómez Acebo, Inés; Altzibar, Jone M.; Jiménez Zabala, Ana; Ardanaz, Eva; Peiró, Rosana

2016-01-01

Background: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. Objectives: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. Methods: A multicenter case?control study was conducted in Spain and Italy in 2008?2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) cont...

De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

Science.gov (United States)

Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

2014-06-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

On the performance of de novo pathway enrichment

DEFF Research Database (Denmark)

Batra, Richa; Alcaraz, Nicolas; Gitzhofer, Kevin

2017-01-01

De novo pathway enrichment is a powerful approach to discover previously uncharacterized molecular mechanisms in addition to already known pathways. To achieve this, condition-specific functional modules are extracted from large interaction networks. Here, we give an overview of the state...

Transferência do fator caturra para o cultivar Mundo Novo de Coffea arabica Transfer of the CT gene to Mundo Novo cultivar

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A. Carvalho

1972-01-01

Full Text Available No presente trabalho são relatados os estudos realizados visando à introdução do gene Ct (caturra que contribui para reduzir a altura da planta, no cultivar Mundo" Novo de Coffea arabica.Estudaram-se, em ensaios de produtividade, as populações Fv F.,, F3 e F4. Nessas populações e principalmente entre os descendentes dos "caféeiros H 2077-2-5 e H 2077-2-12, foram selecionadas plantas homozigotas para os alelos Ct e também para os alelos responsáveis pela cor do fruto xc ou Xc. Essas combinações foram denominadas 'Catuaí Amarelo' e 'Catuaí Vermelho', respectivamente, e suas características são apresentadas. Os novos cultivares vêm-se mostrando de interesse econômico para as regiões cafeeiras não somente pelo porte pequeno, mas também pela produtividade, pelo vigor vegetativo e pela precocidade.The successful transfer of the Ct gene for short internode to the tall cultivar of Coffea arábica'Mundo Novo' is reported. Individual selections were carried out in the F1, F2, F3 and F4 generations. It was found that early selection in the F2 generation was quite effective. A remarkably good correlation was found between productitivity of F2 plants and the yield of the F3 and F4 generations. Plants of the F4 generation have shown reasonable uniformity and high yield in several trials. The new selections showed to be early producers. Two new cultivars were released namely 'Catuaí Amarelo' and 'Catuaí Vermelho'. The former has yellow fruits whereas the latter has red fruits. The plants are much shorter that the ones of Mundo Novo. The new cultivars have a very strong secondary and tertiary branching. Because of these characteristics Catuaí Amarelo and Catuaí Vermelho are being planted in large scale replacing the tall cultivars.

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma.

Science.gov (United States)

Yanamoto, Souichi; Umeda, Masahiro; Kioi, Mitomu; Kirita, Tadaaki; Yamashita, Tetsuro; Hiratsuka, Hiroyoshi; Yokoo, Satoshi; Tanzawa, Hideki; Uzawa, Narikazu; Shibahara, Takahiko; Ota, Yoshihide; Kurita, Hiroshi; Okura, Masaya; Hamakawa, Hiroyuki; Kusukawa, Jingo; Tohnai, Iwai

2018-03-01

The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC). We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m 2 ; subsequent weeks, 250 mg/m 2 ) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m 2 , day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m 2 /day, days 1-4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first. The median follow-up was 10.5 (range 1.2-34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3-4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal. The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease. A motor fMRI study under controlled conditions

International Nuclear Information System (INIS)

Tessa, Carlo; Vignali, Claudio; Lucetti, Claudio; Diciotti, Stefano; Paoli, Lorenzo; Ginestroni, Andrea; Mascalchi, Mario; Cecchi, Paolo; Baldacci, Filippo; Giannelli, Marco; Bonuccelli, Ubaldo

2012-01-01

Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this ''functional deafferentation'' phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of ''8'' figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the ''8''s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. In line with the ''deafferentation hypothesis'', fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD. (orig.)

De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

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Quimsiyeh Mazin

2008-12-01

Full Text Available Abstract Background In routine Assisted Reproductive Technology (ART men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG. Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9(p22.1p24 [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

Divorce and Severity of Coronary Artery Disease: A Multicenter Study

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Amin Daoulah

2017-01-01

Full Text Available The association between marital status and coronary artery disease (CAD is supported by numerous epidemiological studies. While divorce may have an adverse effect on cardiac outcomes, the relationship between divorce and severe CAD is unclear. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period between April 1, 2013, and March 30, 2014. Of 1,068 patients, 124 (12% were divorced. Divorce was more frequent among women (27% compared to men (6%. Most divorced patients had been divorced only once (49%, but a subset had been divorced 2 (38% or ≥3 (12% times. After adjusting for baseline differences, there was no significant association between divorce and severe CAD in men. In women, there was a significant adjusted association between divorce and severe MVD (OR 2.31 [1.16, 4.59] or LMD (OR 5.91 [2.19, 15.99]. The modification of the association between divorce and severe CAD by gender was statistically significant for severe LMD (Pinteraction 0.0008 and marginally significant for CAD (Pinteraction 0.05. Among women, there was a significant adjusted association between number of divorces and severe CAD (OR 2.4 [95% CI 1.2, 4.5], MVD (OR 2.0 [95% CI 1.4, 3.0], and LMD (OR 3.4 [95% CI 1.9, 5.9]. In conclusion, divorce, particularly multiple divorces, is associated with severe CAD, MVD, and LMD in women but not in men.

Multicenter observational prehospital resuscitation on helicopter study.

Science.gov (United States)

Holcomb, John B; Swartz, Michael D; DeSantis, Stacia M; Greene, Thomas J; Fox, Erin E; Stein, Deborah M; Bulger, Eileen M; Kerby, Jeffrey D; Goodman, Michael; Schreiber, Martin A; Zielinski, Martin D; O'Keeffe, Terence; Inaba, Kenji; Tomasek, Jeffrey S; Podbielski, Jeanette M; Appana, Savitri N; Yi, Misung; Wade, Charles E

2017-07-01

at any time point, although only 10% of the high-risk sample were able to be matched. Because of the unexpected imbalance in systolic blood pressure, Glasgow Coma Scale, and Injury Severity Score between systems with and without blood products on helicopters, matching was limited, and the results of this study are inconclusive. With few units transfused to each patient and small outcome differences between groups, it is likely large, multicenter, randomized studies will be required to detect survival differences in this important population. Level II.

High Incidence of De Novo and Subclinical Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy and Cardiac Rhythm Management Device.

Science.gov (United States)

Wilke, Iris; Witzel, Katrin; Münch, Julia; Pecha, Simon; Blankenberg, Stephan; Reichenspurner, Hermann; Willems, Stephan; Patten, Monica; Aydin, Ali

2016-07-01

Atrial fibrillation (AF) is an important prognostic parameter in patients with hypertrophic cardiomyopathy (HCM). Though cardiac rhythm management (CRM) devices (e.g., ICD, pacemaker or implantable loop recorder) can detect subclinical AF, data describing the incidence of AF are rare. We therefore investigated the incidence and clinical impact of de novo and subclinical AF detected by CRM devices in patients with HCM. In our retrospective single-center study, we included patients with HCM and need for CRM devices. The primary endpoint of the study was the incidence of clinical and subclinical de novo AF. During follow-up, patients were screened for adverse events like stroke, ventricular arrhythmia, heart failure, or death. From 192 HCM patients, 44 patients received a CRM device (38 ICDs, 5 pacemakers, 1 implantable loop recorder). In 14 of these patients (32%), AF had been documented before device implantation. Thirty (68%) patients were free from AF at the time of implantation. During a median follow-up of 595 days (interquartile range, 367-890 days), de novo AF was recorded in 16 of these 30 patients (53%). Fourteen (88%) of the 16 patients with de novo AF were free from any clinical symptoms, so these patients were classified to have subclinical AF. In logistic regression analysis, age was the only significant predictor for an increased risk of AF. AF is common in patients with HCM who need a CRM device. More than 50% of these patients develop de novo AF that was predominantly subclinical in our cohort. © 2016 Wiley Periodicals, Inc.

Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

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Hee Jeong Yoo

2015-03-01

Full Text Available Rubinstein-Taybi syndrome (RSTS is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS and Autism diagnostic interview revised (ADI-R to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

Melhoramento do cafeeiro: XXXVIII. Observações sobre progênies do cultivar Mundo-Novo de Coffea arabica na estação experimental de Mococa Coffee breeding: XXXVIII-observation on progenies of the Mundo-Novo cultivars of Coffea arabica in the Mococa experimental station

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Túlio R. Rocha

1980-01-01

Full Text Available Os dados analisados no experimento localizado em Mococa sobre a produtividade de 112 progênies dos cultivares Mundo-Novo S1 e S2, Bourbon-Amarelo, BourbonVermelho e Caturra-Vermelho de Coffea arabica no período de 1955 a 1971, indicaram que as de Mundo-Novo S1, de prefixos MP 474, MP 502, MP 469, MP 492 e MP 475, revelaram-se como as mais produtivas, assemelhando-se a algumas progênies 'Mundo--Novo' S2. Dentre estas, destacou-se a de prefixo MP 388-6, que atingiu o nível mais elevado de produção do experimento. As progênies de 'Mundo-Novo', em conjunto, produziram 44% a mais do que as de Bourbon-Amarelo e, estas, 60% a mais do que as de Bourbon-Vermelho e Caturra-Vermelho. A altura e o diâmetro da copa atingiram valores médios mais elevados para as progênies de 'Mundo-Novo'. Verificaram-se correlações positivas e altamente significativas entre altura média da planta e diâmetro médio da copa com a produção das progênies. As progênies mais produtivas revelaram rendimento (relação entre peso de café maduro e beneficiado de aproximadamente 6,0 e porcentagem de sementes normais, do tipo chato, acima de 80. Quanto ao tamanho das sementes do tipo chato, duas progênies 'Mundo-Novo' S1, MP 474 e MP 452, apresentaram peneira média maior, permi-tindo seleção de plantas com essa característica e com elevada produção.Coffee progenies of the Mundo-Novo cultivars of Coffea arabica were studied in an experiment located at the Mococa Experimental Station of the Instituto Agronômico in comparison with Bourbon-Amarelo, Bourbon-Vermelho and Caturra-Vermelho cultivars of the same species. During a period of 17 consecutive cropping years (1955-1971, Mundo-Novo yielded approximately 44% more than Bourbon-Amarelo and this cultivars yielded 60% more than Bourbon-Vermelho and Caturra-Vermelho. Among the 89 S1 'Mundo-Novo' progenies, MP 474, MP 502, MP 469, MP 492 and MP 475 yielded as much as the two best 'Mundo-Novo' S2 progenies. Greater

Novo Jornalismo: fronteiras litero-factuais em A sangue Frio e em Radical Chique

Directory of Open Access Journals (Sweden)

Francisco Aquinei Timóteo Queirós

2012-03-01

Full Text Available http://dx.doi.org/10.5007/1984-784X.2012v12n18p130 A pesquisa busca analisar de que forma fato e ficção se entrecruzam no “movimento” do Novo Jornalismo, a partir das obras A sangue Frio e Radical Chique e o Novo Jornalismo, de Truman Capote e Tom Wolfe, respectivamente. Pretende-se, a partir da investigação do corpus em estudo, revelar os aspectos que aproximam o fato jornalístico, a notícia e a reportagem às técnicas literárias do romance, do conto e da crônica. O estudo investiga o Novo Jornalismo sob o viés de textos centrais das áreas de teoria literária e estudos jornalísticos utilizando autores como Mikhail Bakhtin, Hayden White, Paul Ricoeur, Muniz Sodré; além de referenciar outros escritores que, como Tom Wolfe e Truman Capote, fizeram parte de um grande movimento renovador do jornalismo literário nos anos 1950, 1960 e 1970 chamado, genericamente, de Novo Jornalismo.

[Immunodiagnosis of endemic mycoses and bronchopulmonary aspergillosis: a multicenter study in Argentina].

Science.gov (United States)

Canteros, C E; Rivas, M C; Soria, M; Lee, W; Perrotta, D; Rodero, L; Davel, G

2004-01-01

In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01-2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order were PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study.

A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

Science.gov (United States)

Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

2018-05-02

The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer

International Nuclear Information System (INIS)

Ishiguro, Megumi; Mori, Masaki; Kakeji, Yoshihiro; Kanazawa, Akiyoshi; Kobayashi, Michiya; Okajima, Masazumi; Hyodo, Ichinosuke; Miyakoda, Keiko; Sugihara, Kenichi; Kotake, Kenjiro; Nishimura, Genichi; Tomita, Naohiro; Ichikawa, Wataru; Takahashi, Keiichi; Watanabe, Toshiaki; Furuhata, Tomohisa; Kondo, Ken

2013-01-01

Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results

Facebook - Um novo espaço autobiográfico?

Directory of Open Access Journals (Sweden)

Maria Tereza Lima

2015-07-01

Full Text Available O arigo "Facebook - Um novo espaço autobiográfico?" tem como objetivo central investigar como a perspectiva autobiográfica e biográfica se configura em uma rede social. Levando em consideração esse novo espaço de exteriorização da memória, analisamos as escolhas de uma pessoa ao postar os mais diversos gêneros textuais no Facebook e verificamos até que ponto tais fragmentos textuais narram a história de um indivíduo. Quais textos são postados? O que foi escolhido e o que foi excluído desse perfil? O autor trava um pacto de leitura com o leitor? Se levarmos em consideração que os textos postados nessa rede social são textos produzidos pelo próprio autor do perfil e de autores diversos, como configuraremos esses espaços virtuais? Autobiográficos e biográficos? Quem escreve a página virtual é o próprio autor do perfil ou múltiplos autores? Com as redes sociais, surge um novo modelo de autobiografia e de biógrafo? Esses e tantos outros questionamentos nortearam nossas investigações e permitiram-nos conhecer um pouco mais sobre as estratégias autobiográficas dos autores virtuais contemporâneos.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

OpenAIRE

Eisenstein, Eric L.; Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2010-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators ...

Interreader agreement in the assessment of magnetic resonance images of rheumatoid arthritis wrist and finger joints--an international multicenter study

DEFF Research Database (Denmark)

Østergaard, Mikkel; Klarlund, Mette; Lassere, M

2001-01-01

and iv Gd (Techniques A and C), these rates were 86% (synovitis) and 97% (bone lesions). Corresponding intraclass correlation coefficients (quadratic weighted kappas) were 0.44-0.68, mean 0.58 (synovitis), and 0.44-0.69, mean 0.62 (bone lesion), i.e., in the moderate to good range. Unweighted kappa...... values were in the low to moderate range, generally lowest for JSN (... in assessing synovitis and bone destruction in RA multicenter studies....

Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates.

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Jia-Yu Chen

2015-07-01

Full Text Available While some human-specific protein-coding genes have been proposed to originate from ancestral lncRNAs, the transition process remains poorly understood. Here we identified 64 hominoid-specific de novo genes and report a mechanism for the origination of functional de novo proteins from ancestral lncRNAs with precise splicing structures and specific tissue expression profiles. Whole-genome sequencing of dozens of rhesus macaque animals revealed that these lncRNAs are generally not more selectively constrained than other lncRNA loci. The existence of these newly-originated de novo proteins is also not beyond anticipation under neutral expectation, as they generally have longer theoretical lifespan than their current age, due to their GC-rich sequence property enabling stable ORFs with lower chance of non-sense mutations. Interestingly, although the emergence and retention of these de novo genes are likely driven by neutral forces, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution, which may contribute to human-specific genetic novelties by taking advantage of existed genomic contexts.

Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

International Nuclear Information System (INIS)

Hashimoto, Muneaki; Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu; Tanaka, Akiko; Aoki, Takashi; Nara, Takeshi

2012-01-01

Highlights: ► We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. ► Disruption of the cpsII gene significantly reduced the growth of epimastigotes. ► In particular, the CPSII-null mutant severely retarded intracellular growth. ► The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes—an insect form—possess both activities, amastigotes—an intracellular replicating form of T. cruzi—are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

Demonstration of de novo synthesis of enzymes by density labelling with stable isotopes

International Nuclear Information System (INIS)

Huebner, G.; Hirschberg, K.

1977-01-01

The technique of in vivo density labelling of proteins with H 2 18 O and 2 H 2 O has been used to investigate hormonal regulation and developmental expression of enzymes in plant cells. Buoyant density data obtained from isopycnic equilibrium centrifugation demonstrated that the cytokinine-induced nitrate reductase activity and the gibberellic acid-induced phosphatase activity in isolated embryos of Agrostemma githago are activities of enzymes synthesized de novo. The increase in alanine-specific aminopeptidase in germinating A. githago seeds is not due to de novo synthesis but to the release of preformed enzyme. On the basis of this result it is possible to apply the enzyme aminopeptidase as an internal density standard in equilibrium centrifugation. Density labelling experiments on proteins in pea cotyledons have been used to study the change in the activity of acid phosphatase, alanine-specific aminopeptidase, and peroxidase during germination. The activities of these enzymes increase in cotyledons of Pisum sativum. Density labelling by 18 O and 2 H demonstrates de novo synthesis of these three enzymes. The differential time course of enzyme induction shows the advantage of using H 2 18 O as labelling substance in cases when the enzyme was synthesized immediately at the beginning of germination. At this stage of development the amino-acid pool available for synthesis is formed principally by means of hydrolysis of storage proteins. The incorporation of 2 H into the new proteins takes place in a measurable amount at a stage of growth in which the amino acids are also synthesized de novo. The enzyme acid phosphatase of pea cotyledons was chosen to demonstrate the possibility of using the density labelling technique to detect protein turnover. (author)

De novo transcriptome assembly of two different peach cultivars grown in Korea

Directory of Open Access Journals (Sweden)

Yeonhwa Jo

2015-12-01

Full Text Available Peach (Prunus persica is one of the most popular stone fruits worldwide. Next generation sequencing (NGS has facilitated genome and transcriptome analyses of several stone fruit trees. In this study, we conducted de novo transcriptome analyses of two peach cultivars grown in Korea. Leaves of two cultivars, referred to as Jangtaek and Mibaek, were harvested and used for library preparation. The two prepared libraries were paired-end sequenced by the HiSeq2000 system. We obtained 8.14 GB and 9.62 GB sequence data from Jangtaek and Mibaek (NCBI accession numbers: SRS1056585 and SRS1056587, respectively. The Trinity program was used to assemble two transcriptomes de novo, resulting in 110,477 (Jangtaek and 136,196 (Mibaek transcripts. TransDecoder identified possible coding regions in assembled transcripts. The identified proteins were subjected to BLASTP search against NCBI's non-redundant database for functional annotation. This study provides transcriptome data for two peach cultivars, which might be useful for genetic marker development and comparative transcriptome analyses.

Adopting De Novo Programming Approach on IC Design Service Firms Resources Integration

Directory of Open Access Journals (Sweden)

James K. C. Chen

2014-01-01

Full Text Available The semiconductor industry has very important position in computer industry, ICT field, and new electronic technology developing. The IC design service is one of key factor of semiconductor industry development. There are more than 365 IC design service firms have been established around Hsinchu Science Park in Taiwan. Building an efficient planning model for IC design service firm resources integrating is very interest issue. This study aims to construct a planning model for IC design service firm implementation resources integration. This study uses the De Novo programming as an approach of criteria alternative to achieve optimal resource allocation on IC design firm. Results show the IC design service firm should conduct open innovation concept and utilizes design outsourcing obtains cost down and enhance IC design service business performance. This plan model of De Novo programming is not only for IC design service firm and also can apply to the other industrial implementation strategic alliance/integrating resource. This plan model is a universal model for the others industries field.

The Key Drivers behind Novo Nordisk’s Growth in the Diabetes Market in China

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Hind Louiza CHITOUR

2013-12-01

Full Text Available To enter the Chinese Pharmaceutical market, “Big Pharma” has adopted different strategies to tackle the challenges specific to the country in terms of size, demographics, specific sales channels and logistics adjustments. While the majority of Global Pharmaceutical players have opted for an aggressive M&A approach to penetrate the Chinese market and gain local insight; the Danish Novo Nordisk has instead chosen a strategy focusing on innovation and developing its R&D structure to capitalize on the local talent pool. To illustrate Novo Nordisk’s growth strategy in the Mainland, we analyzed its competitiveness in the diabetes market by demonstrating the key drivers behind this success. We applied a various set of tools for this research: Novo Nordisk, Dong Bao Pharmaceutical executives’ interviews and personal observations accounting for the primary data, we also reviewed secondary data to perform a PEST analysis in addition to Porter’s competitive advantage model in order to extract the reasons behind Novo Nordisk’s marching success in the Mainland.

Pharmacokinetics and pharmacodynamics of medication in asphyxiated newborns during controlled hypothermia. The PharmaCool multicenter study

Directory of Open Access Journals (Sweden)

de Haan Timo R

2012-05-01

Full Text Available Abstract Background In the Netherlands, perinatal asphyxia (severe perinatal oxygen shortage necessitating newborn resuscitation occurs in at least 200 of the 180–185.000 newly born infants per year. International randomized controlled trials have demonstrated an improved neurological outcome with therapeutic hypothermia. During hypothermia neonates receive sedative, analgesic, anti-epileptic and antibiotic drugs. So far little information is available how the pharmacokinetics (PK and pharmacodynamics (PD of these drugs are influenced by post resuscitation multi organ failure and the metabolic effects of the cooling treatment itself. As a result, evidence based dosing guidelines are lacking. This multicenter observational cohort study was designed to answer the question how hypothermia influences the distribution, metabolism and elimination of commonly used drugs in neonatal intensive care. Methods/Design Multicenter cohort study. All term neonates treated with hypothermia for Hypoxic Ischemic Encephalopathy (HIE resulting from perinatal asphyxia in all ten Dutch Neonatal Intensive Care Units (NICUs will be eligible for this study. During hypothermia and rewarming blood samples will be taken from indwelling catheters to investigate blood concentrations of several antibiotics, analgesics, sedatives and anti-epileptic drugs. For each individual drug the population PK will be characterized using Nonlinear Mixed Effects Modelling (NONMEM. It will be investigated how clearance and volume of distribution are influenced by hypothermia also taking maturation of neonate into account. Similarly, integrated PK-PD models will be developed relating the time course of drug concentration to pharmacodynamic parameters such as successful seizure treatment; pain assessment and infection clearance. Discussion On basis of the derived population PK-PD models dosing guidelines will be developed for the application of drugs during neonatal hypothermia treatment. The

Identifying wrong assemblies in de novo short read primary ...

Indian Academy of Sciences (India)

2016-08-05

Aug 5, 2016 ... Most of these assemblies are done using some de novo short read assemblers and other related approaches. .... benchmarking projects like Assemblathon 1, Assemblathon ... from a large insert library (at least 1000 bases).

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Energy Technology Data Exchange (ETDEWEB)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca [Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta (Canada); Straube, William [Advanced Technology Consortium, Imaged-Guided Therapy QA Center, St. Louis, Missouri (United States); Laurie, Fran [Quality Assurance Review Center, Lincoln, Rhode Island (United States); Followill, David [Radiological Physics Center, University of Texas MD Anderson Cancer Centre, Houston, Texas (United States)

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

International Nuclear Information System (INIS)

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

OpenAIRE

Sheng, Chew Keng; Lim, Chee Kean; Rashidi, Ahmad

2010-01-01

Abstracts Background The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. Aim We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. Me...

De novo structural modeling and computational sequence analysis ...

African Journals Online (AJOL)

Different bioinformatics tools and machine learning techniques were used for protein structural classification. De novo protein modeling was performed by using I-TASSER server. The final model obtained was accessed by PROCHECK and DFIRE2, which confirmed that the final model is reliable. Until complete biochemical ...

The Anti-Osteoporotic Drug Preferences of Physiatrists: A Multicenter Descriptive Study

Directory of Open Access Journals (Sweden)

Yeşim Gökçe Kutsal

2012-08-01

Full Text Available Aim: The purpose of this multicenter descriptive study is to determine the preferences of physiatrists in our country for anti-osteoporotic drugs in patients with primary and secondary osteoporosis. Materials and Methods: This study was carried out in 10 provinces of Turkey. The diagnosis of osteoporosis was based on World Health Organization criteria using dual-energy x-ray absorptiometry. Patients with a spine and/or hip T-score ≤-2.5 were considered as osteoporotic. 714 patients over 18 years old with primary or secondary osteoporosis were included in the study. In addition to socio-demographic characteristics and chronic use of medications and/or additional systemic diseases that cause secondary osteoporosis were questioned and antiosteoporotic drugs that are recommended by their physicians were recorded.Results: The physicians’ preferred vitamin D and calcium as the prior treatment both in primary and secondary osteoporosis. The most commonly used anti-osteoporotic agent was alendronate from the biphosphonate group. It was followed by ibandronate, risedronate, strontium ranelate, calcitonin, zoledronate, raloxifene, parathyroid hormone (PTH and hormone replacement therapy (HRT in the primary osteoporosis and risedronate, ibandronate, calcitonin, strontium ranelate, zoledronate, PTH, HRT and raloxifene in the secondary osteoporosis, respectively. Conclusion: The physician should choose the most suitable treatment for the patient based on fracture risk, medical history, previous treatments for osteoporosis, concomitant diseases, treatment-induced risks and benefits, and the relation between financial cost and potential benefit. (Turkish Journal of Osteoporosis 2012;18: 42-6

Predicting behavioral variant frontotemporal dementia with pattern classification in multi-center structural MRI data

Directory of Open Access Journals (Sweden)

Sebastian Meyer

2017-01-01

Conclusion: Our study demonstrates that MRI, a widespread imaging technology, can individually identify bvFTD with high accuracy in multi-center imaging data, paving the road to personalized diagnostic approaches in the future.

De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

Science.gov (United States)

Idowu, Michael O; Chhatrala, Ravi; Siddiqui, M Bilal; Driscoll, Carolyn; Stravitz, R Todd; Sanyal, Arun J; Bhati, Chandra; Sargeant, Carol; Luketic, Velimir A; Sterling, Richard K; Contos, Melissa; Matherly, Scott; Puri, Puneet; Siddiqui, M Shadab

2015-11-01

Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. © 2015 American Association for the Study of Liver Diseases.

A Pareto Algorithm for Efficient De Novo Design of Multi-functional Molecules.

Science.gov (United States)

Daeyaert, Frits; Deem, Micheal W

2017-01-01

We have introduced a Pareto sorting algorithm into Synopsis, a de novo design program that generates synthesizable molecules with desirable properties. We give a detailed description of the algorithm and illustrate its working in 2 different de novo design settings: the design of putative dual and selective FGFR and VEGFR inhibitors, and the successful design of organic structure determining agents (OSDAs) for the synthesis of zeolites. We show that the introduction of Pareto sorting not only enables the simultaneous optimization of multiple properties but also greatly improves the performance of the algorithm to generate molecules with hard-to-meet constraints. This in turn allows us to suggest approaches to address the problem of false positive hits in de novo structure based drug design by introducing structural and physicochemical constraints in the designed molecules, and by forcing essential interactions between these molecules and their target receptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inflammatory bowel disease after liver transplantation : Risk factors for recurrence and De novo disease

NARCIS (Netherlands)

Verdonka, RC; Dijkstra, G; Haagsma, EB; Shostrom, VK; Van den Berg, AP; Kleibeuker, JH

Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver

Five-Year Pooled Data Analysis of the Ahmed Baerveldt Comparison Study and the Ahmed Versus Baerveldt Study.

Science.gov (United States)

Christakis, Panos G; Zhang, Dongyu; Budenz, Donald L; Barton, Keith; Tsai, James C; Ahmed, Iqbal I K

2017-04-01

To determine the relative efficacy of the Ahmed-FP7 and Baerveldt BG101-350 implants. Pooled analysis of 2 multicenter, randomized clinical trials. A total of 514 patients aged 18 or older with uncontrolled glaucoma that had failed or were at high risk of failing trabeculectomy were randomized to receive an Ahmed implant (n = 267) or Baerveldt implant (n = 247). Cumulative failure rates (using an intraocular pressure [IOP] target of 6-18 mm Hg inclusive), de novo glaucoma surgery rates, mean IOP, mean glaucoma medication use, and visual acuity were compared. Baseline characteristics were similar between groups. Mean preoperative IOP of the study population was 31.5 ± 11.3 mm Hg on an average of 3.3 ± 1.1 glaucoma medications. At 5 years, mean IOP was 15.8 ± 5.2 mm Hg in the Ahmed group and 13.2 ± 4.7 mm Hg in the Baerveldt group (P glaucoma medication use was 1.9 ± 1.5 in the Ahmed group and 1.5 ± 1.4 in the Baerveldt group (P = .007). The cumulative failure rate at 5 years was 49% in the Ahmed group and 37% in the Baerveldt group (P = .007). High IOP was the most common reason for failure in both groups, and de novo glaucoma surgery was required in 16% of the Ahmed group and 8% of the Baerveldt group (P = .006). Failure owing to hypotony occurred in 0.4% of the Ahmed group and 4.5% of the Baerveldt group (P = .002). Visual outcomes were similar between groups (P = .90). The Baerveldt group had a lower failure rate, lower rate of de novo glaucoma surgery, and lower mean IOP on fewer medications than the Ahmed group. Baerveldt implantation carried a higher risk of hypotony. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

International Nuclear Information System (INIS)

Wessling, J.; Schuelke, C.; Koch, R.

2014-01-01

Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

Therapy response evaluation of malignant lymphoma in a multicenter study. Comparison of manual and semiautomatic measurements in CT

Energy Technology Data Exchange (ETDEWEB)

Wessling, J.; Schuelke, C. [Muenster Univ. (Germany). Dept. of Clinical Radiology; Koch, R. [Muenster Univ. (Germany). Dept. of Medical Informatics and Biomathematics; and others

2014-08-15

Purpose: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. Materials and Methods: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. Results: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. Conclusion: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. (orig.)

Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

Directory of Open Access Journals (Sweden)

Chen Xie

2012-09-01

Full Text Available Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA-Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis, which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.

De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder

DEFF Research Database (Denmark)

Hamilton, P J; Campbell, N G; Sharma, S

2013-01-01

De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution...

Novel de novo BRCA2 mutation in a patient with a family history of breast cancer

DEFF Research Database (Denmark)

Hansen, Thomas V O; Bisgaard, Marie Luise; Jønson, Lars

2008-01-01

whole blood. The paternity was determined by single nucleotide polymorphism (SNP) microarray analysis. Parental origin of the de novo mutation was determined by establishing mutation-SNP haplotypes by variant specific PCR, while de novo and mosaic status was investigated by sequencing of DNA from......BACKGROUND: BRCA2 germ-line mutations predispose to breast and ovarian cancer. Mutations are widespread and unclassified splice variants are frequently encountered. We describe the parental origin and functional characterization of a novel de novo BRCA2 splice site mutation found in a patient...... and synthesis of a truncated BRCA2 protein. The aberrant splicing was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. The mutation was not found in any of the patient's parents or in the mother's carcinoma, showing it is a de novo mutation. Variant specific PCR indicates...

Effect of women's age on embryo morphology, cleavage rate and competence-A multicenter cohort study

DEFF Research Database (Denmark)

Grøndahl, Marie Louise; Christiansen, Sofie Lindgren; Kesmodel, Ulrik Schiøler

2017-01-01

This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women's age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding.......0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first...... time, we show that a woman's age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate...

Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

International Nuclear Information System (INIS)

Haigh, Cathryn L.; Drew, Simon C.

2015-01-01

The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation

Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

Energy Technology Data Exchange (ETDEWEB)

Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Drew, Simon C., E-mail: sdrew@unimelb.edu.au [Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010 (Australia)

2015-06-05

The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.

Multi-centered AdS{sub 3} solutions from Virasoro conformal blocks

Energy Technology Data Exchange (ETDEWEB)

Hulík, Ondřej [Institute of Physics of the ASCR,Na Slovance 2, 182 21 Prague 8 (Czech Republic); Institute of Particle Physics and Nuclear Physics,Faculty of Mathematics and Physics, Charles University,V Holešovičkách 2, 180 00 Prague 8 (Czech Republic); Procházka, Tomáš [Arnold Sommerfeld Center for Theoretical Physics,Ludwig Maximilian University of Munich,Theresienstr. 37, D-80333 München (Germany); Raeymaekers, Joris [Institute of Physics of the ASCR,Na Slovance 2, 182 21 Prague 8 (Czech Republic)

2017-03-24

We revisit the construction of multi-centered solutions in three-dimensional anti-de Sitter gravity in the light of the recently discovered connection between particle worldlines and classical Virasoro conformal blocks. We focus on multi-centered solutions which represent the backreaction of point masses moving on helical geodesics in global AdS{sub 3}, and argue that their construction reduces to a problem in Liouville theory on the disk with Zamolodchikov-Zamolodchikov boundary condition. In order to construct the solution one needs to solve a certain monodromy problem which we argue is solved by a vacuum classical conformal block on the sphere in a particular channel. In this way we construct multi-centered gravity solutions by using conformal blocks special functions. We show that our solutions represent left-right asymmetric configurations of operator insertions in the dual CFT. We also provide a check of our arguments in an example and comment on other types of solutions.

Management, nutrition, and lactation performance are related to bulk tank milk de novo fatty acid concentration on northeastern US dairy farms.

Science.gov (United States)

Woolpert, M E; Dann, H M; Cotanch, K W; Melilli, C; Chase, L E; Grant, R J; Barbano, D M

2016-10-01

This study investigated the relationship of management practices, dietary characteristics, milk composition, and lactation performance with de novo fatty acid (FA) concentration in bulk tank milk from commercial dairy farms with Holstein, Jersey, and mixed-breed cows. It was hypothesized that farms with higher de novo milk FA concentrations would more commonly use management and nutrition practices known to optimize ruminal conditions that enhance de novo synthesis of milk FA. Farms (n=44) located in Vermont and northeastern New York were selected based on a history of high de novo (HDN; 26.18±0.94g/100g of FA; mean ± standard deviation) or low de novo (LDN; 24.19±1.22g/100g of FA) FA in bulk tank milk. Management practices were assessed during one visit to each farm in March or April, 2014. Total mixed ration samples were collected and analyzed for chemical composition using near infrared spectroscopy. We found no differences in days in milk at the farm level. Yield of milk fat, true protein, and de novo FA per cow per day were higher for HDN versus LDN farms. The HDN farms had lower freestall stocking density (cows/stall) than LDN farms. Additionally, tiestall feeding frequency was higher for HDN than LDN farms. No differences between HDN and LDN farms were detected for dietary dry matter, crude protein, neutral detergent fiber, starch, or percentage of forage in the diet. However, dietary ether extract was lower for HDN than LDN farms. This research indicates that overcrowded freestalls, reduced feeding frequency, and greater dietary ether extract content are associated with lower de novo FA synthesis and reduced milk fat and true protein yields on commercial dairy farms. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Comparative analysis of MR imaging, Ictal SPECT and EEG in temporal lobe epilepsy: a prospective IAEA multi-center study

Energy Technology Data Exchange (ETDEWEB)

Zaknun, John J. [University Hospital of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); International Atomic Energy Agency (IAEA), Nuclear Medicine Section, Division of Human Health, Vienna (Austria); IAEA, Nuclear Medicine Section, Division of Human Health, Wagramer Strasse 5, P.O. Box 100, Wien (Austria); Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Maes, Alex [Katholieke Universiteit Leuven, Leuven (Belgium); AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); Tepmongkol, Supatporn [Chulalongkorn University, Nuclear Medicine Division, Department of Radiology, Bangkok (Thailand); Vazquez, Silvia [Instituto de Investigaciones Neurologicas, FLENI, Department of Radiology, Buenos Aires (Argentina); Dupont, Patrick [Katholieke Universiteit Leuven, Leuven (Belgium); Dondi, Maurizio [Ospedale Maggiore, Department of Nuclear Medicine, Bologna (Italy); International Atomic Energy Agency (IAEA), Nuclear Medicine Section, Division of Human Health, Vienna (Austria)

2008-01-15

MR imaging, ictal single-photon emission CT (SPECT) and ictal EEG play important roles in the presurgical localization of epileptic foci. This multi-center study was established to investigate whether the complementary role of perfusion SPECT, MRI and EEG for presurgical localization of temporal lobe epilepsy could be confirmed in a prospective setting involving centers from India, Thailand, Italy and Argentina. We studied 74 patients who underwent interictal and ictal EEG, interictal and ictal SPECT and MRI before surgery of the temporal lobe. In all but three patients, histology was reported. The clinical outcome was assessed using Engel's classification. Sensitivity values of all imaging modalities were calculated, and the add-on value of SPECT was assessed. Outcome (Engel's classification) in 74 patients was class I, 89%; class II, 7%; class III, 3%; and IV, 1%. Regarding the localization of seizure origin, sensitivity was 84% for ictal SPECT, 70% for ictal EEG, 86% for MRI, 55% for interictal SPECT and 40% for interictal EEG. Add-on value of ictal SPECT was shown by its ability to correctly localize 17/22 (77%) of the seizure foci missed by ictal EEG and 8/10 (80%) of the seizure foci not detected by MRI. This prospective multi-center trial, involving centers from different parts of the world, confirms that ictal perfusion SPECT is an effective diagnostic modality for correctly identifying seizure origin in temporal lobe epilepsy, providing complementary information to ictal EEG and MRI. (orig.)

Comparative analysis of MR imaging, Ictal SPECT and EEG in temporal lobe epilepsy: a prospective IAEA multi-center study

International Nuclear Information System (INIS)

Zaknun, John J.; Bal, Chandrasekhar; Maes, Alex; Tepmongkol, Supatporn; Vazquez, Silvia; Dupont, Patrick; Dondi, Maurizio

2008-01-01

MR imaging, ictal single-photon emission CT (SPECT) and ictal EEG play important roles in the presurgical localization of epileptic foci. This multi-center study was established to investigate whether the complementary role of perfusion SPECT, MRI and EEG for presurgical localization of temporal lobe epilepsy could be confirmed in a prospective setting involving centers from India, Thailand, Italy and Argentina. We studied 74 patients who underwent interictal and ictal EEG, interictal and ictal SPECT and MRI before surgery of the temporal lobe. In all but three patients, histology was reported. The clinical outcome was assessed using Engel's classification. Sensitivity values of all imaging modalities were calculated, and the add-on value of SPECT was assessed. Outcome (Engel's classification) in 74 patients was class I, 89%; class II, 7%; class III, 3%; and IV, 1%. Regarding the localization of seizure origin, sensitivity was 84% for ictal SPECT, 70% for ictal EEG, 86% for MRI, 55% for interictal SPECT and 40% for interictal EEG. Add-on value of ictal SPECT was shown by its ability to correctly localize 17/22 (77%) of the seizure foci missed by ictal EEG and 8/10 (80%) of the seizure foci not detected by MRI. This prospective multi-center trial, involving centers from different parts of the world, confirms that ictal perfusion SPECT is an effective diagnostic modality for correctly identifying seizure origin in temporal lobe epilepsy, providing complementary information to ictal EEG and MRI. (orig.)

Novel 'heavy' dyes for retinal membrane staining during macular surgery: multicenter clinical assessment

NARCIS (Netherlands)

Veckeneer, Marc; Mohr, Andreas; Alharthi, Essam; Azad, Rajvardhan; Bashshur, Ziad F.; Bertelli, Enrico; Bejjani, Riad A.; Bouassida, Brahim; Bourla, Dan; Crespo, Iñigo Corcóstegui; Fahed, Charbel; Fayyad, Faisal; Mura, Marco; Nawrocki, Jerzy; Rivett, Kelvin; Scharioth, Gabor B.; Shkvorchenko, Dmitry O.; Szurman, Peter; van Wijck, Hein; Wong, Ian Y.; Wong, David S. H.; Frank, Johannes; Oellerich, Silke; Bruinsma, Marieke; Melles, Gerrit R. J.

2014-01-01

Purpose: To evaluate the feasibility of two novel heavy' dye solutions for staining the internal limiting membrane (ILM) and epiretinal membranes (ERMs), without the need for a prior fluid-air exchange, during macular surgery. Methods: In this prospective nonrandomized multicenter cohort study, the

De novo transcriptome assembly of the mycoheterotrophic plant Monotropa hypopitys

Directory of Open Access Journals (Sweden)

Alexey V. Beletsky

2017-03-01

Full Text Available Monotropa hypopitys (pinesap is a non-photosynthetic obligately mycoheterotrophic plant of the family Ericaceae. It obtains the carbon and other nutrients from the roots of surrounding autotrophic trees through the associated mycorrhizal fungi. In order to understand the evolutionary changes in the plant genome associated with transition to a heterotrophic lifestyle, we performed de novo transcriptomic analysis of M. hypopitys using next-generation sequencing. We obtained the RNA-Seq data from flowers, flower bracts and roots with haustoria using Illumina HiSeq2500 platform. The raw data obtained in this study can be available in NCBI SRA database with accession number of SRP069226. A total of 10.3 GB raw sequence data were obtained, corresponding to 103,357,809 raw reads. A total of 103,025,683 reads were filtered after removing low-quality reads and trimming the adapter sequences. The Trinity program was used to de novo assemble 98,349 unigens with an N50 of 1342 bp. Using the TransDecoder program, we predicted 43,505 putative proteins. 38,416 unigenes were annotated in the Swiss-Prot protein sequence database using BLASTX. The obtained transcriptomic data will be useful for further studies of the evolution of plant genomes upon transition to a non-photosynthetic lifestyle and the loss of photosynthesis-related functions.

A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine.

NARCIS (Netherlands)

Beck, D.E.; Cohen, Z.; Fleshman, J.W.; Kaufman, H.S.; Goor, H. van; Wolff, B.G.

2003-01-01

INTRODUCTION: Seprafilm adhesion barrier (Seprafilm) has been proven to prevent adhesion formation after abdominal and pelvic surgery. This article reports safety results, including the postoperative incidence of abdominal and pelvic abscess and pulmonary embolism, from a large, multicenter trial

Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

International Nuclear Information System (INIS)

Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V.

1991-01-01

Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in [ 3 H]glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 μM sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis

Differential effects of pertussis toxin on insulin-stimulated phosphatidylcholine hydrolysis and glycerolipid synthesis de novo. Studies in BC3H-1 myocytes and rat adipocytes

Energy Technology Data Exchange (ETDEWEB)

Hoffman, J.M.; Standaert, M.L.; Nair, G.P.; Farese, R.V. (Univ. of South Florida, Tampa (USA))

1991-04-02

Insulin-induced increases in diacylglycerol (DAG) have been suggested to result from stimulation of de novo phosphatidic acid (PA) synthesis and phosphatidylcholine (PC) hydrolysis. Presently, the authors found that insulin decreased PC levels of BC3H-1 myocytes and rat adipocytes by approximately 10-25% within 30 s. These decreases were rapidly reversed in both cell types, apparently because of increased PC synthesis de novo. In BC3H-1 myocytes, pertussis toxin inhibited PC resynthesis and insulin effects on the pathway of de novo PA-DAG-PC synthesis, as evidenced by changes in ({sup 3}H)glycerol incorporation, but did not inhibit insulin-stimulated PC hydrolysis. Pertussis toxin also blocked the later, but not the initial, increase in DAG production in the myocytes. Phorbol esters activated PC hydrolysis in both myocytes and adipocytes, but insulin-induced stimulation of PC hydrolysis was not dependent upon activation of PKC, since this hydrolysis was not inhibited by 500 {mu}M sangivamycin, an effective PKC inhibitor. The results indicate that insulin increases DAG by pertussis toxin sensitive and insensitive (PC hydrolysis) mechanisms, which are mechanistically separate, but functionally interdependent and integrated. PC hydrolysis may contribute importantly to initial increases in DAG, but later sustained increases are apparently largely dependent on insulin-induced stimulation of the pathway of de novo phospholipid synthesis.

De novo synthesis of milk triglycerides in humans

Science.gov (United States)

Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk tha...

Evaluation of criteria for clinical control in a prospective, international, multicenter study of patients with COPD

DEFF Research Database (Denmark)

Miravitlles, Marc; Sliwinski, Pawel; Rhee, Chin Kook

2018-01-01

BACKGROUND: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHOD: This international, multicenter, prospective study aimed to validate the concept of control in COPD [control = stability (no...... exacerbations or impairment in CAT scores) + low impact (low level of symptoms)]. Data from the screening visit was used to: investigate the level of control, compare characteristics of patients according to the control status, and perform a sensitivity analysis of the levels of control using either clinical...... criteria or questionnaires (COPD Assessment Test -CAT- or Clinical COPD Questionnaire -CCQ-). RESULTS: A total of 314 patients were analysed, mean age was 68.5 years and mean FEV1 was 52.6% of predicted. According to the prespecified criteria 21% of patients were classified as controlled, all of them...

76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

Science.gov (United States)

2011-11-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... for Industry and Food and Drug Administration Staff; De Novo Classification Process (Evaluation of...

Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Atsushi Takata

2018-01-01

Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

Sensitivity-Informed De Novo Programming for Many-Objective Water Portfolio Planning Under Uncertainty

Science.gov (United States)

Kasprzyk, J. R.; Reed, P. M.; Kirsch, B. R.; Characklis, G. W.

2009-12-01

Risk-based water supply management presents severe cognitive, computational, and social challenges to planning in a changing world. Decision aiding frameworks must confront the cognitive biases implicit to risk, the severe uncertainties associated with long term planning horizons, and the consequent ambiguities that shape how we define and solve water resources planning and management problems. This paper proposes and demonstrates a new interactive framework for sensitivity informed de novo programming. The theoretical focus of our many-objective de novo programming is to promote learning and evolving problem formulations to enhance risk-based decision making. We have demonstrated our proposed de novo programming framework using a case study for a single city’s water supply in the Lower Rio Grande Valley (LRGV) in Texas. Key decisions in this case study include the purchase of permanent rights to reservoir inflows and anticipatory thresholds for acquiring transfers of water through optioning and spot leases. A 10-year Monte Carlo simulation driven by historical data is used to provide performance metrics for the supply portfolios. The three major components of our methodology include Sobol globoal sensitivity analysis, many-objective evolutionary optimization and interactive tradeoff visualization. The interplay between these components allows us to evaluate alternative design metrics, their decision variable controls and the consequent system vulnerabilities. Our LRGV case study measures water supply portfolios’ efficiency, reliability, and utilization of transfers in the water supply market. The sensitivity analysis is used interactively over interannual, annual, and monthly time scales to indicate how the problem controls change as a function of the timescale of interest. These results have been used then to improve our exploration and understanding of LRGV costs, vulnerabilities, and the water portfolios’ critical reliability constraints. These results

TRANSPORT OF PATIENTS FOR PRIMARY PTCA FROM GENERAL HOSPITAL NOVO MESTO TO LJUBLJANA IN 2002

Directory of Open Access Journals (Sweden)

Renata Okrajšek

2004-12-01

Full Text Available Background. The treatment of acute coronary syndrome (ACS with ST-segment elevation with primary percutaneous transluminal coronary angioplasty (PTCA is the best way to treat these patients. Primary PTCA is also practicable with patients who are admitted into institution without catheter laboratory. The transport of patients into the tertiary institution is safe, but it is important to keep the time of ischemia as short as possible and to reach the time interval of door-balloon as recommended by the guidelines. The ACS patients with ST-segment elevation that were directed into General Hospital Novo mesto after examination at the internistic emergency department have been redirected to KC Ljubljana for realization of PTCA since October 2001.Methods. A prospective analysis of patients with ACS with STsegment elevation, who had been transferred from General Hospital Novo mesto to KC Ljubljana in the period from January 1, 2002 to December 31, 2002 to have a primary PTCA, was performed. The analysis comprised the following: the time interval of handling the patients at Internistic department of General Hospital Novo mesto, the time of transport of patients to Ljubljana and total time interval from the arrival of patients to General Hospital Novo mesto to the first inflation of balloon in Ljubljana. We monitored the complications that occurred during the treatment of the patients.Results. In the above mentioned period 29 patients (24 males and 5 females were transported from the General Hospital Novo mesto to the KC Ljubljana to have a primary PTCA performed. The total time interval measured between the patients’ arrival to General Hospital Novo mesto to the first inflation of balloon in Ljubljana in the year 2002 was 145 minutes, which is 17 minutes better than in the previous period. The time interval recommended by the guidelines was achieved with four patients.Conclusions. By recognizing the problems that had encountered with directing the

European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay

DEFF Research Database (Denmark)

Krintus, Magdalena; Kozinski, Marek; Boudry, Pascal

2014-01-01

BACKGROUND: International recommendations highlight the superior value of cardiac troponins (cTns) for early diagnosis of myocardial infarction along with analytical requirements of improved precision and detectability. In this multicenter study, we investigated the analytical performance of a ne...

Uridine monophosphate synthetase enables eukaryotic de novo NAD+ biosynthesis from quinolinic acid.

Science.gov (United States)

McReynolds, Melanie R; Wang, Wenqing; Holleran, Lauren M; Hanna-Rose, Wendy

2017-07-07

NAD + biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD + biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD + biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD + biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of de novo NAD + biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact de novo biosynthesis pathway for NAD + from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD + levels and partially reversed NAD + -dependent phenotypes caused by mutation of pnc-1 , which encodes a nicotinamidase required for NAD + salvage biosynthesis, demonstrating contribution of de novo synthesis to NAD + homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD + biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD + biosynthesis creates novel possibilities for manipulating NAD + biosynthetic pathways, which is key for the future of therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Decision making in liver transplant selection committees: a multicenter study.

Science.gov (United States)

Volk, Michael L; Biggins, Scott W; Huang, Mary Ann; Argo, Curtis K; Fontana, Robert J; Anspach, Renee R

2011-10-18

To receive a liver transplant, patients must first be placed on a waiting list-a decision made at most transplant centers by a multidisciplinary committee. The function of these committees has never been studied. To describe decision making in liver transplant committees and identify opportunities for process improvement. Observational multicenter study. 4 liver transplant centers in the United States. 68 members of liver transplant committees across the 4 centers. 63 meetings were observed, and 50 committee members were interviewed. Recorded transcripts and field notes were analyzed by using standard qualitative sociologic methods. Although the structure of the meetings varied by center, the process was uniform and primarily involved inductive reasoning to review possible reasons for patient exclusion. Patients were excluded if they were too well, too sick (in the setting of advanced liver disease), or too old or had nonhepatic comorbid conditions, substance abuse problems, or other psychosocial barriers. Dominant themes in the discussions included member angst over deciding who lived or died, a high correlation between psychosocial barriers to transplantation and the patient's socioeconomic status, and the influence of external forces on decision making. Unwritten center policies and confusion regarding advocacy versus stewardship roles were consistently identified as barriers to effective group decision making. The use of qualitative methods provides broad understanding but limits specific inferences. The 4 centers may not reflect the practices of every transplant center nationwide. The difficult decisions made by liver transplant committees are reasonably consistent and well-intentioned, but the process might be improved by having more explicit written policies and clarifying roles. This may inform resource allocation in other areas of medicine. The Greenwall Foundation and the National Institutes of Health.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM)

NARCIS (Netherlands)

Kemp, Samuel V.; Slebos, Dirk-Jan; Kirk, Alan; Kornaszewska, Malgorzata; Carron, Kris; Ek, Lars; Broman, Gustav; Hillerdal, Gunnar; Mal, Herve; Pison, Christophe; Briault, Amandine; Downer, Nicola; Darwiche, Kaid; Rao, Jagan; Huebner, Ralf-Harto; Ruwwe-Glosenkamp, Christof; Trosini-Desert, Valery; Eberhardt, Ralf; Herth, Felix J.; Derom, Eric; Malfait, Thomas; Shah, Pallav L.; Garner, Justin L.; ten Hacken, Nick H.; Fallouh, Hazem; Leroy, Sylvie; Marquette, Charles H.

2017-01-01

Rationale: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. Objectives: To evaluate the efficacy and safety of Zephyr EBVs

Thoracic Duct Injury Following Cervical Spine Surgery: A Multicenter Retrospective Review

OpenAIRE

Derakhshan, Adeeb; Lubelski, Daniel; Steinmetz, Michael P.; Corriveau, Mark; Lee, Sungho; Pace, Jonathan R.; Smith, Gabriel A.; Gokaslan, Ziya; Bydon, Mohamad; Arnold, Paul M.; Fehlings, Michael G.; Riew, K. Daniel; Mroz, Thomas E.

2017-01-01

Study Design: Multicenter retrospective case series. Objective: To determine the rate of thoracic duct injury during cervical spine operations. Methods: A retrospective case series study was conducted among 21 high-volume surgical centers to identify instances of thoracic duct injury during anterior cervical spine surgery. Staff at each center abstracted data for each identified case into case report forms. All case report forms were collected by the AOSpine North America Clinical Research Ne...

De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

International Nuclear Information System (INIS)

Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

1986-01-01

The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. 14 C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of 14 C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types

Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study.

Science.gov (United States)

Preziosa, Paolo; Rocca, Maria A; Pagani, Elisabetta; Stromillo, Maria Laura; Enzinger, Christian; Gallo, Antonio; Hulst, Hanneke E; Atzori, Matteo; Pareto, Deborah; Riccitelli, Gianna C; Copetti, Massimiliano; De Stefano, Nicola; Fazekas, Franz; Bisecco, Alvino; Barkhof, Frederik; Yousry, Tarek A; Arévalo, Maria J; Filippi, Massimo

2016-04-01

In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. © 2016 Wiley Periodicals, Inc.

Spectral flow, and the spectrum of multicenter solutions

International Nuclear Information System (INIS)

Bena, Iosif; Bobev, Nikolay; Warner, Nicholas P.

2008-01-01

We discuss 'spectral-flow' coordinate transformations that take asymptotically four-dimensional solutions into other asymptotically four-dimensional solutions. We find that spectral flow can relate smooth three-charge solutions with a multicenter Taub-NUT base to solutions where one or several Taub-NUT centers are replaced by two-charge supertubes, and vice versa. We further show that multiparameter spectral flows can map such Taub-NUT centers to more singular centers that are either D2-D0 or pure D0-brane sources. Since supertubes can depend on arbitrary functions, we establish that the moduli space of smooth horizonless black-hole microstate solutions is classically of infinite dimension. We also use the physics of supertubes to argue that some multicenter solutions that appear to be bound states from a four-dimensional perspective are in fact not bound states when considered from a five- or six-dimensional perspective

De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.

Science.gov (United States)

Stanik, Juraj; Dusatkova, Petra; Cinek, Ondrej; Valentinova, Lucia; Huckova, Miroslava; Skopkova, Martina; Dusatkova, Lenka; Stanikova, Daniela; Pura, Mikulas; Klimes, Iwar; Lebl, Jan; Gasperikova, Daniela; Pruhova, Stepanka

2014-03-01

MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A). Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing. Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo. In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.

De novo point mutations in patients diagnosed with ataxic cerebral palsy.

Science.gov (United States)

Parolin Schnekenberg, Ricardo; Perkins, Emma M; Miller, Jack W; Davies, Wayne I L; D'Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O'Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis; Jackson, Mandy; Tucker, Stephen J; Németh, Andrea H

2015-07-01

Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

Model-Based GUI Testing Using Uppaal at Novo Nordisk

DEFF Research Database (Denmark)

H. Hjort, Ulrik; Rasmussen, Jacob Illum; Larsen, Kim Guldstrand

2009-01-01

This paper details a collaboration between Aalborg University and Novo Nordiskin developing an automatic model-based test generation tool for system testing of the graphical user interface of a medical device on an embedded platform. The tool takes as input an UML Statemachine model and generates...

Towards accurate de novo assembly for genomes with repeats

NARCIS (Netherlands)

Bucur, Doina

2017-01-01

De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

The prevalence of sacroilitis in psoriatic arthritis: new perspectives from a large, multicenter cohort. A Department of Veterans Affairs Cooperative Study

International Nuclear Information System (INIS)

Battistone, M.J.; Clegg, D.O.; Manaster, B.J.; Reda, D.J.

1999-01-01

Objective. To determine the prevalence of radiographic evidence of sacroiliitis in a large population of patients with psoriatic arthritis. Patients and design. Patients were recruited from 15 clinical centers. This was part of a large, multicenter study of patients with an established diagnosis of ankylosing spondylitis, psoriatic arthritis, or reactive arthritis. For this cohort, an established diagnosis of psoriatic arthritis was required, with cutaneous manifestations and involvement of at least three appendicular joints. At entry, patients were not selected for the presence of axial involvement. Radiographs - one anteroposterior view of the pelvis and one oblique view of each sacroiliac joint - were graded using the New York classification scale by a musculoskeletal radiologist masked to the specific diagnosis and clinical symptoms. Re-evaluation of 10% of the films 3 years later quantified intraobserver variability. Results. Two hundred and two patients with psoriatic arthritis were studied. Duration of the disease averaged 12 years; all patients had psoriasis and peripheral arthritis. The prevalence of radiographic evidence of sacroiliitis (grade 2 or higher) was 78%; 71% of these had grade 3 disease. Conclusions. Previously reported prevalence of sacroiliitis in patients with psoriatic arthritis ranges from 30% to 50%. The prevalence of radiographic evidence of sacroiliitis in this large multicenter cohort of patients with appendicular psoriatic arthritis was substantially higher. (orig.)

The prevalence of sacroilitis in psoriatic arthritis: new perspectives from a large, multicenter cohort. A Department of Veterans Affairs Cooperative Study

Energy Technology Data Exchange (ETDEWEB)

Battistone, M.J.; Clegg, D.O. [Division of Rheumatology, University of Utah Medical Center, Salt Lake City, UT (United States)]|[Department of Medicine, Division of Rheumatology, Veterans Affairs Medical Center, Salt Lake City, UT (United States); Manaster, B.J. [Department of Radiology, Division of Musculoskeletal Imaging, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA (United States); Reda, D.J. [Cooperative Studies Program Coordinating Center, VA Hospital, Hines, IL (United States)

1999-04-01

Objective. To determine the prevalence of radiographic evidence of sacroiliitis in a large population of patients with psoriatic arthritis. Patients and design. Patients were recruited from 15 clinical centers. This was part of a large, multicenter study of patients with an established diagnosis of ankylosing spondylitis, psoriatic arthritis, or reactive arthritis. For this cohort, an established diagnosis of psoriatic arthritis was required, with cutaneous manifestations and involvement of at least three appendicular joints. At entry, patients were not selected for the presence of axial involvement. Radiographs - one anteroposterior view of the pelvis and one oblique view of each sacroiliac joint - were graded using the New York classification scale by a musculoskeletal radiologist masked to the specific diagnosis and clinical symptoms. Re-evaluation of 10% of the films 3 years later quantified intraobserver variability. Results. Two hundred and two patients with psoriatic arthritis were studied. Duration of the disease averaged 12 years; all patients had psoriasis and peripheral arthritis. The prevalence of radiographic evidence of sacroiliitis (grade 2 or higher) was 78%; 71% of these had grade 3 disease. Conclusions. Previously reported prevalence of sacroiliitis in patients with psoriatic arthritis ranges from 30% to 50%. The prevalence of radiographic evidence of sacroiliitis in this large multicenter cohort of patients with appendicular psoriatic arthritis was substantially higher. (orig.) With 3 figs., 4 tabs., 29 refs.

Optimization of treatment protocols to prevent de novo development of antibiotic resistance in Pseudomonas aeruginosa

NARCIS (Netherlands)

Feng, Yanfang

2016-01-01

The ever-increasing rate of drug resistant bacteria has been one of the most challenging problem worldwide. This thesis studied the following subjects with mostly the clinically leading pathogen, P. aeruginosa, as the model strain: de novo development of antibiotic resistance in patient during the

A multicenter study on objective and subjective benefits with a transcutaneous bone-anchored hearing aid device

DEFF Research Database (Denmark)

Hougaard, Dan Dupont; Boldsen, Soren Kjaergaard; Jensen, Anne Marie

2017-01-01

Examination of objective as well as subjective outcomes with a new transcutaneous bone-anchored hearing aid device. The study was designed as a prospective multicenter consecutive case-series study involving tertiary referral centers at two Danish University Hospitals. A total of 23 patients were...... implanted. Three were lost to follow-up. Patients had single-sided deafness, conductive or mixed hearing loss. Intervention: Rehabilitative. Aided and unaided sound field hearing was evaluated objectively using (1) pure warble tone thresholds, (2) pure-tone average (PTA4), (3) speech discrimination score...... (SDS) in quiet, and (4) speech reception threshold 50% at 70 dB SPL noise level (SRT50%). Subjective benefit was evaluated by three validated questionnaires: (1) the IOI-HA, (2) the SSQ-12, and (3) a questionnaire evaluating both the frequency and the duration of hearing aid usage. The mean aided PTA4...

Fibromyalgia as a cause of uncontrolled asthma: a case-control multicenter study.

Science.gov (United States)

Martinez-Moragon, Eva; Plaza, Vicente; Torres, Isabel; Rosado, Ana; Urrutia, Isabel; Casas, Xavier; Hinojosa, Belen; Blanco-Aparicio, Marina; Delgado, Julio; Quirce, Santiago; Sabadell, Carles; Cebollero, Pilar; Muñoz-Fernández, Ana

2017-12-01

Fibromyalgia can affect the control of asthma when both diseases are present in a single patient. To characterize asthma in patients with concomitant fibromyalgia to assess whether fibromyalgia is an independent factor of asthma severity that influences poor asthma control. We also evaluated how dyspnea is perceived by patients in order to demonstrate that alterations in the perception of airway obstruction may be responsible for poor asthma control. This was a cross-sectional case-control multicenter study, in which 56 patients in the asthma and fibromyalgia group were matched to 36 asthmatics by sex, approximate age, and asthma severity level. All patients were women. Study variables included the Asthma Control Test (ACT), the Mini Asthma Quality of Life Questionnaire (MiniAQLQ), the Nijmegen hyperventilation syndrome questionnaire, the Hospital Anxiety and Depression Scale, and perception of dyspnea after acute bronchoconstriction. Although patients in both study groups showed similar asthma severity and use of anti-asthmatic drugs, patients in the asthma and fibromyalgia group showed lower scores on the ACT and MiniAQLQ questionnaires, and higher scores of anxiety and depression as well as hyperventilation compared to asthma patients without fibromyalgia. All these differences were statistically significant. Fibromyalgia in patients with asthma influences poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life. Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly.

Ethics Review of Pediatric Multi-Center Drug Trials

NARCIS (Netherlands)

Needham, Allison C.; Kapadia, Mufiza Z.; Offringa, Martin

2015-01-01

The assessment of safety and efficacy of therapeutics for children and adolescents requires the use of multi-centered designs. However, the need to obtain ethical approval from multiple independent research ethics boards (REBs) presents as a challenge to investigators and sponsors who must consider

Fiscal 1999 feasibility study on energy conservation at Novo-oil refinery in Ufa City

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-03-31

An energy conservation plan was examined for Novo oil refinery of Bashneftechim Company in Ufa City, Bashkortstan, Russia for the purpose of making the plan tied to the COP3 joint implementation. The objective units in the study include an atmospheric and vacuum distillation unit with throughput of 7.8 million tons/year, a visbreaker and a vacuum gas oil hydrodesulfurization unit (for feedstock of FCC in Lenin Refinery), and a catalytic cracking unit, for example. Energy conservation measures are improvement and revamping of heating furnace to control excess air ratio in furnace, installation of air pre-heater or heat recovery boiler to recover heat from exhaust gas of heating furnace, additional installation of heat exchangers to recover heat from product oils, and efficiency improvement of overall operation by modernization of instrumentation and controlling equipment. The policy is not complete rebuilding of the facilities but utilizing the existing facilities by improving energy efficiency as far as possible. The study shows that investment for energy saving will be recovered within 3-6 years in many cases while total investment is estimated to be 1.5-3.0 billion yen. Total reduction of fuel consumption will be 500-800 million yen. Yearly reduction of CO2 emission will amount to 0.29 million tons (23%). (NEDO)

Trends in Radical Surgical Treatment Methods for Breast Malignancies in China: A Multicenter 10-Year Retrospective Study.

Science.gov (United States)

Zhang, Bai-Lin; Sivasubramaniam, Priya G; Zhang, Qian; Wang, Jing; Zhang, Bin; Gao, Ji-Dong; Tang, Zhong-Hua; Chen, Guo-Ji; Xie, Xiao-Ming; Wang, Zhongzhao; Yang, Hong-Jian; He, Jian-Jun; Li, Hui; Li, Jia-Yuan; Fan, Jin-Hu; Wang, Xiang; Qiao, You-Lin

2015-09-01

Incidence rates of breast cancer continue to rise in the People's Republic of China. The purpose of this study was to describe Chinese trends in radical surgical modalities and influential imaging and demographic factors for breast malignancies. This study was a hospital-based, multicenter, 10-year (1999-2008), retrospective study. Descriptive statistical tests were used to illustrate information regarding radical surgical trends for the treatment of breast malignancies. Chi-square tests were used to assess effect of demographic factors in addition to imaging and pathological data on the specific surgical method. A total of 4,211 patients were enrolled in the survey. Among them, 3,335 patients with stage 0 to stage III disease undergoing mastectomy or breast-conserving surgery (BCS) were included in the final analysis. The rate of BCS increased from 1.53% in 1999 to 11.88% in 2008. The rate of mastectomy declined over this time period, from 98.47% in 1999 to 88.12% in 2008, with increasing use of diagnostic imaging methods and pathological biopsies. A significantly greater percentage of patients with office work, high education levels, unmarried status, younger age, and early pathological stages preferred BCS compared with mastectomy. Rates of mastectomy in China remain elevated due to diagnosis at higher stages; however, because of increased use of diagnostic imaging, improvement of biopsy methods, and patient education, rates of less invasive lumpectomy are increasing and rates of mastectomy have decreased in China. In this study, 4,211 cases were collected from 1999 to 2008 through a multicenter retrospective study of varying geographic and socioeconomic areas to illustrate trends of surgeries in the People's Republic of China. The correlations between demographic and tumor characteristics and among methods of surgical treatment were explored. This study shows that the rate of breast-conserving surgery (BCS) increased and the rate of mastectomy declined over

Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies

DEFF Research Database (Denmark)

Kajdasz, Daniel K; Iyengar, Smriti; Desaiah, Durisala

2007-01-01

peripheral neuropathic pain (DPNP). METHODS: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as >or=30...

Heterologous aggregates promote de novo prion appearance via more than one mechanism.

Directory of Open Access Journals (Sweden)

Fatih Arslan

2015-01-01

Full Text Available Prions are self-perpetuating conformational variants of particular proteins. In yeast, prions cause heritable phenotypic traits. Most known yeast prions contain a glutamine (Q/asparagine (N-rich region in their prion domains. [PSI+], the prion form of Sup35, appears de novo at dramatically enhanced rates following transient overproduction of Sup35 in the presence of [PIN+], the prion form of Rnq1. Here, we establish the temporal de novo appearance of Sup35 aggregates during such overexpression in relation to other cellular proteins. Fluorescently-labeled Sup35 initially forms one or a few dots when overexpressed in [PIN+] cells. One of the dots is perivacuolar, colocalizes with the aggregated Rnq1 dot and grows into peripheral rings/lines, some of which also colocalize with Rnq1. Sup35 dots that are not near the vacuole do not always colocalize with Rnq1 and disappear by the time rings start to grow. Bimolecular fluorescence complementation failed to detect any interaction between Sup35-VN and Rnq1-VC in [PSI+][PIN+] cells. In contrast, all Sup35 aggregates, whether newly induced or in established [PSI+], completely colocalize with the molecular chaperones Hsp104, Sis1, Ssa1 and eukaryotic release factor Sup45. In the absence of [PIN+], overexpressed aggregating proteins such as the Q/N-rich Pin4C or the non-Q/N-rich Mod5 can also promote the de novo appearance of [PSI+]. Similar to Rnq1, overexpressed Pin4C transiently colocalizes with newly appearing Sup35 aggregates. However, no interaction was detected between Mod5 and Sup35 during [PSI+] induction in the absence of [PIN+]. While the colocalization of Sup35 and aggregates of Rnq1 or Pin4C are consistent with the model that the heterologous aggregates cross-seed the de novo appearance of [PSI+], the lack of interaction between Mod5 and Sup35 leaves open the possibility of other mechanisms. We also show that Hsp104 is required in the de novo appearance of [PSI+] aggregates in a [PIN

KeyPathwayMiner - De-novo network enrichment by combining multiple OMICS data and biological networks

DEFF Research Database (Denmark)

Baumbach, Jan; Alcaraz, Nicolas; Pauling, Josch K.

We tackle the problem of de-novo pathway extraction. Given a biological network and a set of case-control studies, KeyPathwayMiner efficiently extracts and visualizes all maximal connected sub-networks that contain mainly genes that are dysregulated, e.g., differentially expressed, in most cases ...

Surgical outcomes of robot-assisted rectal cancer surgery using the da Vinci Surgical System: a multi-center pilot Phase II study.

Science.gov (United States)

Tsukamoto, Shunsuke; Nishizawa, Yuji; Ochiai, Hiroki; Tsukada, Yuichiro; Sasaki, Takeshi; Shida, Dai; Ito, Masaaki; Kanemitsu, Yukihide

2017-12-01

We conducted a multi-center pilot Phase II study to examine the safety of robotic rectal cancer surgery performed using the da Vinci Surgical System during the introduction period of robotic rectal surgery at two institutes based on surgical outcomes. This study was conducted with a prospective, multi-center, single-arm, open-label design to assess the safety and feasibility of robotic surgery for rectal cancer (da Vinci Surgical System). The primary endpoint was the rate of adverse events during and after robotic surgery. The secondary endpoint was the completion rate of robotic surgery. Between April 2014 and July 2016, 50 patients were enrolled in this study. Of these, 10 (20%) had rectosigmoid cancer, 17 (34%) had upper rectal cancer, and 23 (46%) had lower rectal cancer; six underwent high anterior resection, 32 underwent low anterior resection, 11 underwent intersphincteric resection, and one underwent abdominoperineal resection. Pathological stages were Stage 0 in 1 patient, Stage I in 28 patients, Stage II in 7 patients and Stage III in 14 patients. Pathologically complete resection was achieved in all patients. There was no intraoperative organ damage or postoperative mortality. Eight (16%) patients developed complications of all grades, of which 2 (4%) were Grade 3 or higher, including anastomotic leakage (2%) and conversion to open surgery (2%). The present study demonstrates the feasibility and safety of robotic rectal cancer surgery, as reflected by low morbidity and low conversion rates, during the introduction period. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

De novo mutations in the genome organizer CTCF cause intellectual disability

DEFF Research Database (Denmark)

Gregor, Anne; Oti, Martin; Kouwenhoven, Evelyn N

2013-01-01

An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift...... mutations and one de novo missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates...... and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three individuals with point mutations revealed deregulation of genes involved in signal transduction...

Burnout Among Otolaryngology Residents in Saudi Arabia: A Multicenter Study.

Science.gov (United States)

Aldrees, Turki; Badri, Motasim; Islam, Tahera; Alqahtani, Khalid

2015-01-01

Determine the prevalence of, and associated risk factors for, burnout among otolaryngologist residents in Saudi Arabia. A cross-section study of multicenter hospitals in Saudi Arabia conducted in March 2013. Registered residents in Saudi Otolaryngology Board Program. The Maslach Burnout Inventory was used to measure burnout status. Questions supplementary to the Maslach Burnout Inventory were also included to identify associated potential risk factors such as demographic data, resident satisfaction, and work conditions. Of the initial 123 questionnaires that were distributed, 85 yielded responses, a rate of 69%. The mean age (standard deviation [SD]) of respondents was 29 (2.3) years. Of those, 67% (57/85) were men and 66% (55/85) were married. Resident levels were delineated: level 2, 19%; level 3, 33%; level 4, 29%; and level 5, 19%. The mean number of on-call days/month (SD) was 7 (2), clinics/week (SD) was 3 (1), sleep hours/day (SD) was 6 (1), and operations/week (SD) was 2 (1). The mean emotional exhaustion (EE) and depersonalization scores were high at 29.5 (SD = 9.6) and 10.7 (SD = 6), respectively. The mean personal accomplishment was low at 32.33 (SD = 6). The mean of all subscales did not differ by sex (EE p = 0.5; depersonalization p = 0.09; personal accomplishment p = 0.4). Mean EE differed by marital status, which was 31.2, 31.3, and 25.6 for married, divorced, and single, respectively, analysis of variance test p = 0.045. Burnout prevalence was found to be high among otolaryngologist residents in Saudi Arabia. The associated variables examined in this study should be addressed to decrease this level of burnout and provide residents with a less stressful work environment. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Determination of serum albumin, analytical challenges: a French multicenter study.

Science.gov (United States)

Rossary, Adrien; Blondé-Cynober, Françoise; Bastard, Jean-Philippe; Beauvieux, Marie-Christine; Beyne, Pascale; Drai, Jocelyne; Lombard, Christine; Anglard, Ingrid; Aussel, Christian; Claeyssens, Sophie; Vasson, Marie-Paule

2017-06-01

Among the biological markers of morbidity and mortality, albumin holds a key place in the range of criteria used by the High Authority for Health (HAS) for the assessment of malnutrition and the coding of information system medicalization program (PMSI). If the principle of quantification methods have not changed in recent years, the dispersion of external evaluations of the quality (EEQ) data shows that the standardization using the certified reference material (CRM) 470 is not optimal. The aim of this multicenter study involving 7 sites, conducted by a working group of the French Society of Clinical Biology (SFBC), was to assess whether the albuminemia values depend on the analytical system used. The albumin from plasma (n=30) and serum (n=8) pools was quantified by 5 different methods [bromocresol green (VBC) and bromocresol purple (PBC) colorimetry, immunoturbidimetry (IT), immunonephelometry (IN) and capillary electrophoresis (CE)] using 12 analyzers. Bland and Altman's test evaluated the difference between the results obtained by the different methods. For example, a difference as high as 13 g/L was observed for the same sample between the methods (p albumin across the range of values tested compared to PBC (p albumin values inducing a difference of performance between the immunoprecipitation methods (IT vs IN, p albumin results are related to the technical/analyzer tandem used. This variability is usually not taken into account by the clinician. Thus, clinicians and biologists have to be aware and have to check, depending on the method used, the albumin thresholds identified as risk factors for complications related to malnutrition and PMSI coding.

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

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Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Icarus: visualizer for de novo assembly evaluation.

Science.gov (United States)

Mikheenko, Alla; Valin, Gleb; Prjibelski, Andrey; Saveliev, Vladislav; Gurevich, Alexey

2016-11-01

: Data visualization plays an increasingly important role in NGS data analysis. With advances in both sequencing and computational technologies, it has become a new bottleneck in genomics studies. Indeed, evaluation of de novo genome assemblies is one of the areas that can benefit from the visualization. However, even though multiple quality assessment methods are now available, existing visualization tools are hardly suitable for this purpose. Here, we present Icarus-a novel genome visualizer for accurate assessment and analysis of genomic draft assemblies, which is based on the tool QUAST. Icarus can be used in studies where a related reference genome is available, as well as for non-model organisms. The tool is available online and as a standalone application. http://cab.spbu.ru/software/icarus CONTACT: aleksey.gurevich@spbu.ruSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

NARCIS (Netherlands)

de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

De novo transcriptome assembly of shrimp Palaemon serratus

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Alejandra Perina

2017-03-01

Full Text Available The shrimp Palaemon serratus is a coastal decapod crustacean with a high commercial value. It is harvested for human consumption. In this study, we used Illumina sequencing technology (HiSeq 2000 to sequence, assemble and annotate the transcriptome of P. serratus. RNA was isolated from muscle of adults individuals and, from a pool of larvae. A total number of 4 cDNA libraries were constructed, using the TruSeq RNA Sample Preparation Kit v2. The raw data in this study was deposited in NCBI SRA database with study accession number of SRP090769. The obtained data were subjected to de novo transcriptome assembly using Trinity software, and coding regions were predicted by TransDecoder. We used Blastp and Sma3s to annotate the identified proteins. The transcriptome data could provide some insight into the understanding of genes involved in the larval development and metamorphosis.

In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

DEFF Research Database (Denmark)

Henriksen, O; de Certaines, J D; Spisni, A

1993-01-01

and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took......T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI......, whereas no significant variations were seen for T2. Our in vivo data were generally in reasonable agreement with proposed models based on ex vivo measurements....

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

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Richard J Allen

2017-03-01

Full Text Available Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate of the pathway as a whole.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

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Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients.

Science.gov (United States)

Min, Sang-Il; Ha, Jongwon; Kim, Yon Su; Ahn, Sang Hyun; Park, Taejin; Park, Dae Do; Kim, Suh Min; Min, Seung-Kee; Hong, Hyejin; Ahn, Curie; Kim, Sang Joon

2013-12-01

There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation. A prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months. On Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0) (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized C(max) (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P PK profiles evaluated at 9 months showed that generic substitution also resulted in an 'early and high C(max)'. Efficacy and safety data were comparable over the 9-month study period. Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

De Novo Coding Variants Are Strongly Associated with Tourette Disorder

DEFF Research Database (Denmark)

Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

2017-01-01

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 ...

Hypoactivation of the primary sensorimotor cortex in de novo Parkinson's disease. A motor fMRI study under controlled conditions

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Tessa, Carlo; Vignali, Claudio [Versilia Hospital, AUSL Versilia, Division of Radiology, Camaiore (Italy); Lucetti, Claudio [Versilia Hospital, AUSL Versilia, Division of Neurology, Camaiore (Italy); Diciotti, Stefano; Paoli, Lorenzo; Ginestroni, Andrea; Mascalchi, Mario [University of Florence, Radiodiagnostic Section, Department of Clinical Physiopathology, Florence (Italy); Cecchi, Paolo; Baldacci, Filippo [University of Pisa, Department of Neuroscience, Pisa (Italy); Giannelli, Marco [Azienda Ospedaliero-Universitaria Pisana, Unit of Medical Physics, Pisa (Italy); Bonuccelli, Ubaldo [Versilia Hospital, AUSL Versilia, Division of Neurology, Camaiore (Italy); University of Pisa, Department of Neuroscience, Pisa (Italy)

2012-03-15

Nuclear medicine studies in Parkinson's disease (PD) indicate that nigrostriatal damage causes a widespread cortical hypoactivity assumed to be due to reduced excitatory thalamic outflow. However, so far, functional MRI (fMRI) studies have provided controversial data about this ''functional deafferentation'' phenomenon. To further clarify this issue, we assessed, with fMRI, de novo drug-naive PD patients using a relatively complex motor task under strictly controlled conditions. Nineteen de novo PD patients with right-predominant or bilateral symptoms and 13 age-matched healthy volunteers performed continuous writing of ''8'' figures with the right-dominant hand using a MR-compatible device that enables identification of incorrectly performed tasks and measures the size and the frequency of the ''8''s. The data were analyzed with FSL software and correlated with the clinical severity rated according to the Hoehn and Yahr (HY) staging system. Fifteen (89%) of 19 PD patients and 12 (92%) of 13 controls correctly executed the task. PD patients showed significant hypoactivation of the left primary sensorimotor cortex (SM1) and cerebellum and no hyperactive areas as compared to controls. However, activation in SM1 and supplementary motor area bilaterally, in left supramarginal, parietal inferior, parietal superior and frontal superior gyri as well as in right parietal superior and angular gyri paralleled increasing disease severity as assessed with the HY stage. In line with the ''deafferentation hypothesis'', fMRI demonstrates hypoactivation of the SM1 in the early clinical stage of PD. (orig.)

Combined therapy with peritoneal dialysis and hemodialysis: a multicenter retrospective observational cohort study in Japan.

Science.gov (United States)

Maruyama, Yukio; Yokoyama, Keitaro; Nakayama, Masaaki; Higuchi, Chieko; Sanaka, Tsutomu; Tanaka, Yoshihide; Sakai, Ken; Mizuiri, Sonoo; Otsuka, Yasushi; Kuriyama, Satoru; Maeba, Teruhiko; Iwasawa, Hideaki; Nakao, Toshiyuki; Hosoya, Tatsuo

2014-01-01

Combining peritoneal dialysis (PD) and hemodialysis (HD) has been common treatment option in Japan. In this retrospective, multicenter, observational study, the clinical characteristics and outcomes of 104 patients (57 ± 11 years, males 72%) who had switched from PD alone to combined therapy with PD and HD were studied. Clinical parameters were measured at baseline and after 3 months of combined therapy. At baseline, urine volume, dialysate-to-plasma ratio of creatinine (D/P Cr), and total Kt/V were 150 ml/day (range: 0-2,000 ml/day), 0.67 ± 0.11, and 1.8 ± 0.4, respectively. During the first 3 months of combined therapy, body weight, urine volume, serum creatinine level, and D/P Cr decreased, whereas hemoglobin levels increased. In patients where PD does not result in acceptable outcomes, combined therapy with PD and HD may have potential benefits in terms of dialysis adequacy and hydration status. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=368389 © 2014 S. Karger AG, Basel.

De Novo Construction of Redox Active Proteins.

Science.gov (United States)

Moser, C C; Sheehan, M M; Ennist, N M; Kodali, G; Bialas, C; Englander, M T; Discher, B M; Dutton, P L

2016-01-01

Relatively simple principles can be used to plan and construct de novo proteins that bind redox cofactors and participate in a range of electron-transfer reactions analogous to those seen in natural oxidoreductase proteins. These designed redox proteins are called maquettes. Hydrophobic/hydrophilic binary patterning of heptad repeats of amino acids linked together in a single-chain self-assemble into 4-alpha-helix bundles. These bundles form a robust and adaptable frame for uncovering the default properties of protein embedded cofactors independent of the complexities introduced by generations of natural selection and allow us to better understand what factors can be exploited by man or nature to manipulate the physical chemical properties of these cofactors. Anchoring of redox cofactors such as hemes, light active tetrapyrroles, FeS clusters, and flavins by His and Cys residues allow cofactors to be placed at positions in which electron-tunneling rates between cofactors within or between proteins can be predicted in advance. The modularity of heptad repeat designs facilitates the construction of electron-transfer chains and novel combinations of redox cofactors and new redox cofactor assisted functions. Developing de novo designs that can support cofactor incorporation upon expression in a cell is needed to support a synthetic biology advance that integrates with natural bioenergetic pathways. © 2016 Elsevier Inc. All rights reserved.

Novo-desenvolvimento, capital social e desigualdade social

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Ana Cristina de Oliveira Oliveira

2012-03-01

Full Text Available Este artigo aborda a tendência de enfrentamento da desigualdade social a partir, no campo econômico, da versão do novo-desenvolvimentismo e, no campo político e ideológico, a partir da noção de capital social, na tentativa de realizar um "capitalismo com face mais humana". Discutiremos duas ordens de questões, considerando a especificidade da formação social brasileira de capitalismo dependente: 1 a “construção de Estados fortes” para

Macrolide use and the risk of vascular disease in HIV-infected men in the Multicenter AIDS Cohort Study

DEFF Research Database (Denmark)

Woolley, Ian J; Li, Xiuhong; Jacobson, Lisa P

2007-01-01

of macrolide prophylaxis on those outcomes. METHODS: A subcohort analysis was undertaken using data collected in the Multicenter AIDS Cohort Study to examine the relative risk of vascular events (myocardial infarction, unstable angina and ischaemic stroke). Cox proportional hazard model using age as the time...... scale with time varying cofactors obtained at each semi-annual visit were used to assess the independent effect of macrolide use. RESULTS: Controlling for other significant effects including race and smoking, HIV-infection was not independently associated with vascular events. Increased risk......BACKGROUND: There has been increasing concern that HIV-infected individuals may be more at risk for cardiovascular events in the highly-active antiretroviral therapy (HAART) era. This study examined the risk of thromboembolic events in HIV-infected and non-infected individuals and the effect...

De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

Science.gov (United States)

Zarrei, Mehdi; Fehlings, Darcy L; Mawjee, Karizma; Switzer, Lauren; Thiruvahindrapuram, Bhooma; Walker, Susan; Merico, Daniele; Casallo, Guillermo; Uddin, Mohammed; MacDonald, Jeffrey R; Gazzellone, Matthew J; Higginbotham, Edward J; Campbell, Craig; deVeber, Gabrielle; Frid, Pam; Gorter, Jan Willem; Hunt, Carolyn; Kawamura, Anne; Kim, Marie; McCormick, Anna; Mesterman, Ronit; Samdup, Dawa; Marshall, Christian R; Stavropoulos, Dimitri J; Wintle, Richard F; Scherer, Stephen W

2018-02-01

PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

Clinicopathological Features of Ocular Adnexal Mantle-Cell Lymphoma in an International Multicenter Cohort

DEFF Research Database (Denmark)

Knudsen, Marina K H; Rasmussen, Peter K; Coupland, Sarah E

2017-01-01

Importance: To our knowledge, the clinical features of ocular adnexal mantle-cell lymphoma (OA-MCL) have not previously been evaluated in a large multicenter cohort. Objective: To characterize the clinical features of OA-MCL. Design, Setting, and Participants: This retrospective multicenter study...... included patient data collected from January 1, 1980, through December 31, 2015, at 6 eye cancer centers in 4 countries. Medical records of 55 patients with OA-MCL were reviewed; the median length of follow-up was 33 months. Main Outcomes and Measures: Overall survival, disease-specific survival....... Overall survival rates for the entire cohort were 65% at 3 years (95% CI, 52%-78%) and 34% at 5 years (95% CI, 21%-47%). Disease-specific survival after 5 years was 38% for the entire cohort (95% CI, 25%-51%); the disease-specific survival adjusted by eye cancer center was better in patients who had...

A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

Science.gov (United States)

Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

2015-09-01

Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

DEFF Research Database (Denmark)

Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki

2012-01-01

and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation...... affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3....

CIPESC® Curitiba: o trabalho da enfermagem no Distrito Bairro Novo CIPESC® Curitiba: el trabajo de enfermería en el Districto Bairro Novo CIPESC® Curitiba: the work of nursing at Bairro Novo District

Directory of Open Access Journals (Sweden)

Denise Maria Altino

2006-08-01

Full Text Available Curitiba implantou em rede o sistema Classificação Internacional das Práticas de Enfermagem em Saúde Coletiva - CIPESC®. O presente estudo objetivou identificar as atividades exercidas pelos profissionais de enfermagem nas unidades de saúde do distrito Bairro Novo de Curitiba. Trata-se de uma pesquisa descritiva em que foram entrevistados auxiliares e enfermeiras utilizando-se de um check-list. Os resultados mostram que: o acolhimento é realizado por todos; as auxiliares se ocupam mais das atividades assistencial-procedimentais; a totalidade das enfermeiras realiza consulta de enfermagem diariamente, recorrendo ao prontuário eletrônico de base CIPESC®. Conclui-se que, excetuando-se as atividades de pesquisa, houve intensificação e ampliação das atividades assistenciais sistematizadas e embasadas no trabalho cotidiano da enfermagem, intra e extramuros.Curitiba implantó el sistema Clasificación Internacional de las Prácticas de Enfermería en Salud Colectiva - CIPESC®. El presente estudio objetivó identificar las actividades ejercidas por personal de enfermería en la red de atención básica de la salud del distrito Bairro Novo, Curitiba. Ha hecho una investigación junto a los trabajadores de enfermería, recorriendo-se a check-list. Los resultados mostrarán: todos realizan el acogimiento; las auxiliares de enfermería se ocupan más de las actividades asistencial-procedimentales; todas las enfermeras realizan consulta de enfermería diariamente, utilizando-se del prontuario electrónico bases CIPESC®. En conclusión, excepto las actividades del investigación, hube intensificación y ampliación de las actividades asistenciales, que se ubican sistematizadas e embasadas en el trabajo cotidiano de la enfermería, así como la educación y planeamiento.Curitiba has been utilized system CIPESC® - International Nursing Practice Classification in Collective Health. This study goal identifies the activities of nursing staff in

Multicenter transversal two-phase study to determine a national prevalence of epilepsy in Algeria.

Science.gov (United States)

Moualek, Dalila; Pacha, Lamia Ali; Abrouk, Samira; Kediha, Mohamed Islam; Nouioua, Sonia; Aissa, Leila Ait; Bellatache, Mounia; Belarbi, Soreya; Slimani, Saddek; Khennouf, Houria; Fellahi, Lynda; El Amine Hamimed, Mohamed; Benali, Nadia; Chekkour, Mohamed Chahine; Maamoun, Ramdane; Dameche, Rachida; Assami, Salima; Tazir, Meriem

2012-01-01

The prevalence of epilepsy in Algeria is unknown. The aims of this multicenter transversal study were to determine the national prevalence and clinical characteristics of epilepsy in the Algerian population. This two-phase study was conducted in 5 circumscriptions and included 8,046 subjects aged over 2 months who attended the randomly selected public and private primary care clinics. In the phase 1 study, a questionnaire was submitted to the sample of patients. In the phase 2 study, all potentially epileptic people were examined by neurologists and a second questionnaire was submitted, eventually assessed by appropriate investigations. Sixty-seven patients were identified as having active epilepsy, giving a crude prevalence ratio of 8.32 per 1,000 (95% CI, 6.34-10.3) and an age-adjusted prevalence ratio of 8.9 per 1,000. The highest age-specific ratio was found in patients aged 10-19 years (16.92 per 1,000). Generalized seizures (68.7%) were more common than partial seizures (29.8%). Perinatal injuries were the major leading putative causes (11.9%). The prevalence of epilepsy of 8.32 determined in this study is relatively high. These results provide new epidemiological data and suggest that epilepsy remains an important public health issue to consider in Algeria. Copyright © 2012 S. Karger AG, Basel.

Preliminary report: prescription of prism-glasses by the Measurement and Correction Method of H.-J. Haase or by conventional orthoptic examination: a multicenter, randomized, double-blind, cross-over study

NARCIS (Netherlands)

Simonsz, H. J.; van Els, J.; Ruijter, J. M.; Bakker, D.; Spekreijse, H.

2001-01-01

In a multicenter, randomized, double-blind, cross-over study in the Netherlands, the effectiveness of (prism-)glasses prescribed by the Measurement and Correction Method of H.-J. Haase (MKH) was compared to that of glasses prescribed by conventional orthoptic examination. Nine pairs of

"Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

Science.gov (United States)

Cubero, Daniel I G; Fumis, Renata Rego Lins; de Sá, Thiago Hérick; Dettino, Aldo; Costa, Felipe Osório; Van Eyll, Brigitte M R H Adam; Beato, Carlos; Peria, Fernanda Maris; Mota, Augusto; Altino, José; Azevedo, Sérgio Jobim; da Rocha Filho, Duílio Reis; Moura, Melba; Lessa, Álvaro Edson Ramos; Del Giglio, Auro

2016-09-01

Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

Position in the second stage of labour and de novo onset of post-partum urinary incontinence.

Science.gov (United States)

Serati, Maurizio; Di Dedda, Maria Carmela; Bogani, Giorgio; Sorice, Paola; Cromi, Antonella; Uccella, Stefano; Lapenna, Martina; Soligo, Marco; Ghezzi, Fabio

2016-02-01

The aim of this study was to evaluate the role of the maternal position at the time of delivery on the onset of de novo symptoms of urinary incontinence (UI) in the post-partum period. This prospective study evaluated the data of consecutive women undergoing labour and delivery, between January 2014 and July 2014. We included only women with a singleton pregnancy undergoing vaginal delivery. During the study period, patients chose to deliver in the position that they considered the most comfortable. The onset of UI was evaluated according to the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-sf). Overall, 716 primiparous women were included in the study. Sixty women refused the 12-week post-partum interview (8.4%). Women were divided in two groups: 296 women (45.1%) who chose an upright position during delivery (group 1) and 360 women (54.9%) who chose a supine position (group 2). Group 1 had a significantly lower episiotomy rate, but a higher rate of greater than second degree perineal tears. In group 1 we found a significantly lower rate of de novo UI (40.5% vs 48.9%, p = 0.03) and in particular of stress urinary incontinence. Via multivariate analysis, birth position was the only factor correlating with the occurrence of urinary incontinence in the post-partum period (OR: 1.52; 95%CI: 1.06, 2.18; p = 0.02). Upright positions at delivery are related to a lower episiotomy rate and a higher rate of greater than second degree perineal tears. Supine positions are an independent risk factor for the onset of de novo UI.

Quantitative multi-parameter mapping of R1, PD*, MT and R2* at 3T: a multi-center validation

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Nikolaus eWeiskopf

2013-06-01

Full Text Available Multi-center studies using magnetic resonance imaging facilitate studying small effect sizes, global population variance and rare diseases. The reliability and sensitivity of these multi-center studies crucially depend on the comparability of the data generated at different sites and time points. The level of inter-site comparability is still controversial for conventional anatomical T1-weighted MRI data. Quantitative multi-parameter mapping (MPM was designed to provide MR parameter measures that are comparable across sites and time points, i.e., 1mm high-resolution maps of the longitudinal relaxation rate (R1=1/T1, effective proton density (PD*, magnetization transfer saturation (MT and effective transverse relaxation rate (R2*=1/T2*. MPM was validated at 3T for use in multi-center studies by scanning five volunteers at three different sites. We determined the inter-site bias, inter-site and intra-site coefficient of variation (CoV for typical morphometric measures (i.e., gray matter probability maps used in voxel-based morphometry and the four quantitative parameters. The inter-site bias and CoV were smaller than 3.1% and 8%, respectively, except for the inter-site CoV of R2* (< 20%. The gray matter probability maps based on the MT parameter maps had a 14% higher inter-site reproducibility than maps based on conventional T1-weighted images. The low inter-site bias and variance in the parameters and derived gray matter probability maps confirm the high comparability of the quantitative maps across sites and time points. The reliability, short acquisition time, high resolution and the detailed insights into the brain microstructure provided by MPM makes it an efficient tool for multi-center imaging studies.

[Enterococcal endocarditis: a multicenter study of 76 cases].

Science.gov (United States)

Martínez-Marcos, Francisco Javier; Lomas-Cabezas, José Manuel; Hidalgo-Tenorio, Carmen; de la Torre-Lima, Javier; Plata-Ciézar, Antonio; Reguera-Iglesias, José María; Ruiz-Morales, Josefa; Márquez-Solero, Manuel; Gálvez-Acebal, Juan; de Alarcón-González, Arístides

2009-12-01

Although enterococci occupy the third position among microorganisms producing infectious endocarditis (IE) following streptococci and Staphylococcus aureus, few multicenter studies have provided an in-depth analysis of enterococcal IE. Description of the characteristics of 76 cases of enterococcal left-sided infectious endocarditis (LSIE) (native: 59, prosthetic: 17) retrieved from the database of the Cardiovascular Infections Study Group of the Andalusian Society of Infectious Diseases, with emphasis on the comparison with non-enterococcal LSIE. Enterococci were the causal agent in 76 of the 696 episodes of LSIE (11%). Compared with non-enterococcal LSIE, enterococcal LSIE was more commonly seen in patients older than 65 (47.4% vs. 27.6%, P<0.0005), and those with chronic diseases (75% vs. 54.6%, P<0.001), calcified valves (18.6% vs. 10%, P<0.05), and previous urinary (30.3% vs. 2.1%, P<0.00001) or abdominal (10.5% vs. 3.1%, P<0.01) infections, and produced a higher rate of relapses (6.6% vs. 2.3%, P<0.05). Enterococcal LSIE was associated with fewer peripheral vascular or skin manifestations (14.5% vs. 27.1%, P<0.05) and fewer immunological phenomena (10.5% vs. 24%, P<0.01). Among the total of patients with enterococcal LSIE, 36.8% underwent valve surgery during hospitalization. In-hospital mortality was 32.9% for enterococcal LSIE, 9.3% for viridans group streptococci (VGS) LSIE and 48.6% for S. aureus LSIE (enterococci vs VGS: P<0.0001; enterococci vs S. aureus: P=0.02). Enterococcal LSIE patients treated with the combination of a penicillin or vancomycin plus an aminoglycoside (n=60) and those treated with ampicillin plus ceftriaxone (n=6) showed similar in-hospital mortality (26.7% vs 33.3%, P=0.66). High-level resistance to gentamicin was detected in 5 of 38 episodes of enterococcal LSIE (13.1%). Enterococcal LSIE appears in patients with well-defined clinical characteristics, and causes few peripheral vascular or skin manifestations and few immunological

MOG-IgG in NMO and related disorders: A multicenter study of 50 patients. Part 2

DEFF Research Database (Denmark)

Jarius, Sven; Ruprecht, Klemens; Kleiter, Ingo

2016-01-01

), and electrophysiological features of a large cohort of MOG-IgG-positive patients with optic neuritis (ON) and/or myelitis (n=50) as well as attack and long-term treatment outcomes. Methods: Retrospective multicenter study. Results: The sex ratio was 1:2.8 (m:f). Median age at onset was 31years (range 6-70). The disease......; end-of-dose relapses occurred 9-12 months after the first infusion. Coexisting autoimmunity was rare (9%). Wingerchuk's 2006 and 2015 criteria for NMO(SD) and Barkhof and McDonald criteria for multiple sclerosis (MS) were met by 28%, 32%, 15%, 33%, respectively; MS had been suspected in 36%. Disease...... severe disease course and the short median time to second attack support the use of prophylactic long-term treatments in patients with MOG-IgG-positive ON and/or myelitis. © 2016 The Author(s)....

The impact of skin diseases on quality of life: A multicenter study.

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Sanclemente, G; Burgos, C; Nova, J; Hernández, F; González, C; Reyes, M I; Córdoba, N; Arévalo, Á; Meléndez, E; Colmenares, J; Ariza, S; Hernández, G

2017-04-01

To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. To determine the impact in quality of life of skin diseases in a Colombian population. This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p=0.37), symptoms (p=0.71) and emotions (p=0.32) domains, whereas statistical differences were found in the function domain (p=0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

Change in Care Dependency of Stroke Patients: A Longitudinal and Multicenter Study.

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Nursiswati, Nursiswati; Halfens, Ruud J G; Lohrmann, Christa

2017-06-01

The study was conducted to investigate the change of care dependency in stroke patients from inpatient wards and outpatient units in Indonesia. This study is longitudinal and multicentered. One hundred and nine patients were included from four hospitals on the island of Java. Care dependency was assessed using the Indonesian version of the 15-item Care Dependency Scale (CDS) at five points in time: at inpatient wards for admission and discharge and at outpatient units after discharge in the 1st week, the 5th week, and the 13th week. Most of the patients were male (65.1%), and diagnosed with ischemic stroke (71.5%). The results showed that care dependency in stroke patients decreased significantly from admission to discharge, as well as from the 5th to the 13th week as measured by the CDS. At admission, 23.0% of the patients were completely dependent on care, and at the 13th week about 1.0% were. Patients' care dependency decreased significantly in all care dependency items of the CDS in the inpatient ward, but five care dependency items of the CDS did not significantly decrease in the outpatient unit. Based on the findings of this study, we recommend that hospital-based and community-based services should include continual care dependence monitoring using this comprehensive instrument. Care dependency is subject to change over time, therefore nurses have to plan and tailor adequate nursing care measures to patient needs in the different stages, especially with respect to the aspect of mobility. Copyright © 2017. Published by Elsevier B.V.

De Novo Assembly and Characterization of the Transcriptome of Grasshopper Shirakiacris shirakii

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Zhongying Qiu

2016-07-01

Full Text Available Background: The grasshopper Shirakiacris shirakii is an important agricultural pest and feeds mainly on gramineous plants, thereby causing economic damage to a wide range of crops. However, genomic information on this species is extremely limited thus far, and transcriptome data relevant to insecticide resistance and pest control are also not available. Methods: The transcriptome of S. shirakii was sequenced using the Illumina HiSeq platform, and we de novo assembled the transcriptome. Results: Its sequencing produced a total of 105,408,878 clean reads, and the de novo assembly revealed 74,657 unigenes with an average length of 680 bp and N50 of 1057 bp. A total of 28,173 unigenes were annotated for the NCBI non-redundant protein sequences (Nr, NCBI non-redundant nucleotide sequences (Nt, a manually-annotated and reviewed protein sequence database (Swiss-Prot, Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG databases. Based on the Nr annotation results, we manually identified 79 unigenes encoding cytochrome P450 monooxygenases (P450s, 36 unigenes encoding carboxylesterases (CarEs and 36 unigenes encoding glutathione S-transferases (GSTs in S. shirakii. Core RNAi components relevant to miroRNA, siRNA and piRNA pathways, including Pasha, Loquacious, Argonaute-1, Argonaute-2, Argonaute-3, Zucchini, Aubergine, enhanced RNAi-1 and Piwi, were expressed in S. shirakii. We also identified five unigenes that were homologous to the Sid-1 gene. In addition, the analysis of differential gene expressions revealed that a total of 19,764 unigenes were up-regulated and 4185 unigenes were down-regulated in larvae. In total, we predicted 7504 simple sequence repeats (SSRs from 74,657 unigenes. Conclusions: The comprehensive de novo transcriptomic data of S. shirakii will offer a series of valuable molecular resources for better studying insecticide resistance, RNAi and molecular marker discovery in the transcriptome.

Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

Institute of Scientific and Technical Information of China (English)

Massimiliano Rizzi; Silvia Mazzuoli; Nunzia Regano; Rosa Inguaggiato; Margherita Bianco; Gioacchino Leandro; Elisabetta Bugianesi; Donatella Noè; Nicoletta Orzes; Paolo Pallini; Maria Letizia Petroni; Gianni Testino; Francesco William Guglielmi

2016-01-01

AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last threesix months. Values of Malnutrition Universal Screening Tool(MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment(MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.

Multicenter study of antimicrobial susceptibility of anaerobic bacteria in Korea in 2012.

Science.gov (United States)

Lee, Yangsoon; Park, Yeon Joon; Kim, Mi Na; Uh, Young; Kim, Myung Sook; Lee, Kyungwon

2015-09-01

Periodic monitoring of regional or institutional resistance trends of clinically important anaerobic bacteria is recommended, because the resistance of anaerobic pathogens to antimicrobial drugs and inappropriate therapy are associated with poor clinical outcomes. There has been no multicenter study of clinical anaerobic isolates in Korea. We aimed to determine the antimicrobial resistance patterns of clinically important anaerobes at multiple centers in Korea. A total of 268 non-duplicated clinical isolates of anaerobic bacteria were collected from four large medical centers in Korea in 2012. Antimicrobial susceptibility was tested by the agar dilution method according to the CLSI guidelines. The following antimicrobials were tested: piperacillin, piperacillin-tazobactam, cefoxitin, cefotetan, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, metronidazole, and tigecycline. Organisms of the Bacteroides fragilis group were highly susceptible to piperacillin-tazobactam, imipenem, and meropenem, as their resistance rates to these three antimicrobials were lower than 6%. For B. fragilis group isolates and anaerobic gram-positive cocci, the resistance rates to moxifloxacin were 12-25% and 11-13%, respectively. Among B. fragilis group organisms, the resistance rates to tigecycline were 16-17%. Two isolates of Finegoldia magna were non-susceptible to chloramphenicol (minimum inhibitory concentrations of 16-32 mg/L). Resistance patterns were different among the different hospitals. Piperacillin-tazobactam, cefoxitin, and carbapemems are highly active beta-lactam agents against most of the anaerobes. The resistance rates to moxifloxacin and tigecycline are slightly higher than those in the previous study.

Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study

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Marie Sylvianne Rabodoarivelo

2018-01-01

Full Text Available Background: In low-income countries, rapid detection of tuberculosis (TB drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF and isoniazid (INH resistance. Methods: This was a multicenter study. Molecular detection of RIF and INH resistance was performed directly from smear-positive TB sputa spotted on a slide, FTA card, GenoCard, and ethanol using the Genotype MTBDRplus assay. The performance of the DNA extraction method from each storage support to detect drug resistance was assessed by calculating their sensitivity and specificity compared to the phenotypic method. Results: From all sites, the overall sensitivity and specificity for RIF-resistance detection was 88% and 85%, respectively, for slides, 86% and 92%, respectively, for GenoCard, 87% and 89%, respectively, for FTA card, and 88% and 92%, respectively, for ethanol. For INH-resistance detection, the overall sensitivity and specificity was 82% and 90%, respectively, for slides, 85% and 96%, respectively, for GenoCard, 86% and 92%, respectively, for FTA card, and 86% and 94%, respectively, for ethanol. Conclusion: Smear slides and filter cards showed to be very useful tools to facilitate DNA extraction from sputum samples with the potential to accelerate the detection of drug resistance in remote areas.

Detection of multidrug-resistant tuberculosis from stored DNA Samples: A multicenter study.

Science.gov (United States)

Rabodoarivelo, Marie Sylvianne; Brandao, A; Cergole Novella, M C; C Bombonatte, A G; Imperiale, B; Rakotosamimanana, N; Morcillo, N; Rasolofo, V; Palomino, J C; Martin, A

2018-01-01

In low-income countries, rapid detection of tuberculosis (TB) drug resistance is often restricted by the difficulties of transporting and storing sputum samples from remote health centers to the reference laboratories where molecular tests are available. The aim of this study was to evaluate the performance of four transport and storage systems for molecular detection of rifampicin (RIF) and isoniazid (INH) resistance. This was a multicenter study. Molecular detection of RIF and INH resistance was performed directly from smear-positive TB sputa spotted on a slide, FTA card, GenoCard, and ethanol using the Genotype MTBDRplus assay. The performance of the DNA extraction method from each storage support to detect drug resistance was assessed by calculating their sensitivity and specificity compared to the phenotypic method. From all sites, the overall sensitivity and specificity for RIF-resistance detection was 88% and 85%, respectively, for slides, 86% and 92%, respectively, for GenoCard, 87% and 89%, respectively, for FTA card, and 88% and 92%, respectively, for ethanol. For INH-resistance detection, the overall sensitivity and specificity was 82% and 90%, respectively, for slides, 85% and 96%, respectively, for GenoCard, 86% and 92%, respectively, for FTA card, and 86% and 94%, respectively, for ethanol. Smear slides and filter cards showed to be very useful tools to facilitate DNA extraction from sputum samples with the potential to accelerate the detection of drug resistance in remote areas.

In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

Science.gov (United States)

Buchanan, Kyle D; Torguson, Rebecca; Rogers, Toby; Xu, Linzhi; Gai, Jiaxiang; Ben-Dor, Itsik; Suddath, William O; Satler, Lowell F; Waksman, Ron

2018-03-13

Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p stent technique and should motivate the continued development of fully bioresorbable scaffolds. Copyright © 2018 Elsevier Inc. All rights reserved.

De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability

NARCIS (Netherlands)

Küry, Sébastien; van Woerden, Geeske M; Besnard, Thomas; Proietti Onori, Martina; Latypova, Xénia; Towne, Meghan C; Cho, Megan T.; Prescott, Trine E; Ploeg, Melissa A; Sanders, Jan-Stephan; Stessman, Holly A F; Pujol, Aurora; Distel, Ben; Robak, Laurie A; Bernstein, Jonathan A; Denommé-Pichon, Anne-Sophie; Lesca, Gaëtan; Sellars, Elizabeth A; Berg, Jonathan; Carré, Wilfrid; Busk, Øyvind Løvold; van Bon, Bregje W M; Waugh, Jeff L; Deardorff, Matthew; Hoganson, George E; Bosanko, Katherine B; Johnson, Diana S; Dabir, Tabib; Holla, Øystein Lunde; Sarkar, Ajoy; Tveten, Kristian; de Bellescize, Julitta; Braathen, Geir J; Terhal, Paulien A; Grange, Dorothy K; van Haeringen, Arie; Lam, Christina; Mirzaa, Ghayda; Burton, Jennifer; Bhoj, Elizabeth J.; Douglas, Jessica; Santani, Avni B; Nesbitt, Addie I; Helbig, Katherine L; Andrews, Marisa V; Begtrup, Amber; Tang, Sha; van Gassen, Koen L I; Juusola, Jane; Foss, Kimberly; Enns, Gregory M; Moog, Ute; Hinderhofer, Katrin; Paramasivam, Nagarajan; Lincoln, Sharyn; Kusako, Brandon H; Lindenbaum, Pierre; Charpentier, Eric; Nowak, Catherine B; Cherot, Elouan; Simonet, Thomas; Ruivenkamp, Claudia A L; Hahn, Sihoun; Brownstein, Catherine A; Xia, Fan; Schmitt, Sébastien; Deb, Wallid; Bonneau, Dominique; Nizon, Mathilde; Quinquis, Delphine; Chelly, Jamel; Rudolf, Gabrielle; Sanlaville, Damien; Parent, Philippe; Gilbert-Dussardier, Brigitte; Toutain, Annick; Sutton, Vernon R; Thies, Jenny; Peart-Vissers, Lisenka E L M; Boisseau, Pierre; Vincent, Marie; Grabrucker, Andreas M; Dubourg, Christèle; Tan, Wen-Hann; Verbeek, Nienke E; Granzow, Martin; Santen, Gijs W E; Shendure, Jay; Isidor, Bertrand; Pasquier, Laurent; Redon, Richard; Yang, Yaping; State, Matthew W; Kleefstra, Tjitske; Cogné, Benjamin; Petrovski, Slavé; Retterer, Kyle; Eichler, Evan E.; Rosenfeld, Jill A; Agrawal, Pankaj B; Bézieau, Stéphane; Odent, Sylvie; Elgersma, Ype; Mercier, Sandra

2017-01-01

Calcium/calmodulin-dependent protein kinase II (CAMK2) is one of the first proteins shown to be essential for normal learning and synaptic plasticity in mice, but its requirement for human brain development has not yet been established. Through a multi-center collaborative study based on a

JTP-103237, a monoacylglycerol acyltransferase inhibitor, prevents fatty liver and suppresses both triglyceride synthesis and de novo lipogenesis

Directory of Open Access Journals (Sweden)

Chihiro Okuma

2015-07-01

Conclusion: In the present study, JTP-103237 prevented carbohydrate-induced fatty liver and suppressed both TG synthesis and de novo lipogenesis, suggesting MGAT inhibitor may prevent carbohydrate-induced metabolic disorders, including NAFLD, obesity and diabetes.

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

Science.gov (United States)

2013-01-01

Background Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis. Methods This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates. Discussion This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

Science.gov (United States)

O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Multi-Center Traffic Management Advisor Operational Field Test Results

Science.gov (United States)

Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

2005-01-01

The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

Aripiprazole for Irritability in Asian Children and Adolescents with Autistic Disorder: A 12-Week, Multinational, Multicenter, Prospective Open-Label Study.

Science.gov (United States)

Kim, Hyo-Won; Park, Eun-Jin; Kim, Ji-Hoon; Boon-Yasidhi, Vitharon; Tarugsa, Jariya; Reyes, Alexis; Manalo, Stella; Joung, Yoo-Sook

2018-04-24

We investigated the effectiveness and tolerability of aripiprazole in the treatment of irritability in Asian children and adolescents (6-17 years) with autistic disorder in a 12-week, multinational, multicenter, open-label study. Sixty-seven subjects (10.0 ± 3.1 years old, 52 boys) were enrolled and treated with flexibly dosed aripiprazole for 12 weeks (mean dose, 5.1 ± 2.5 mg; range 2-15 mg). Aripiprazole significantly reduced the mean caregiver-rated scores for the Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech subscales of the Aberrant Behavior Checklist from baseline to week 12 (p autistic disorder. Further studies with larger sample sizes and longer treatment durations are required.

Prevalence of pilomatricoma in Turner syndrome: findings from a multicenter study.

Science.gov (United States)

Handler, Marc Z; Derrick, Kristina M; Lutz, Richard E; Morrell, Dean S; Davenport, Marsha L; Armstrong, April W

2013-05-01

The absence of data on the prevalence of pilomatricoma among patients with Turner syndrome served as the catalyst for this multicenter investigation. To ascertain the prevalence of pilomatricoma among patients with Turner syndrome and to determine any association between the development of pilomatricomas and the use of exogenous hormones in patients with Turner syndrome. A retrospective medical record review from January 1, 2000, through January 1, 2010, was performed of all patients with Turner syndrome. Data on pilomatricomas and the use of hormone therapy were collected. University of California-Davis Medical Center, University of Nebraska Medical Center, and The University of North Carolina at Chapel Hill. Patients with a diagnosis of Turner syndrome. Prevalence of concomitant pilomatricoma and diagnosis of Turner syndrome. Secondary outcome measures included the use of the exogenous hormones estrogen or recombinant human growth hormone (rhGH). In total, 311 patients with Turner syndrome were identified from these 3 institutions. Among them, 8 patients (2.6%) were diagnosed as having pilomatricomas. Before the development of pilomatricomas, 5 patients had been treated with rhGH but not estrogen, 1 patient had received estrogen but not rhGH, and 2 patients did not receive either therapy. Although the prevalence of pilomatricoma among the general population is unknown, this study demonstrates a high prevalence (2.6%) of pilomatricomas among patients with Turner syndrome. No apparent relationship was noted among our patients or in the literature between the use of rhGH and the development of pilomatricomas.

ICA-based artifact removal diminishes scan site differences in multi-center resting-state fMRI

NARCIS (Netherlands)

R.A. Feis (Rogier A.); S.M. Smith (Stephen); N. Filippini (Nicola); G. Douaud (Gwenaëlle); E.G.P. Dopper (Elise); V. Heise (Verena); A.J. Trachtenberg (Aaron J.); J.C. van Swieten (John); M.A. van Buchem (Mark); S.A.R.B. Rombouts (Serge); C.E. Mackay (Clare E.)

2015-01-01

textabstractResting-state fMRI (R-fMRI) has shown considerable promise in providing potential biomarkers for diagnosis, prognosis and drug response across a range of diseases. Incorporating R-fMRI into multi-center studies is becoming increasingly popular, imposing technical challenges on data

The NOVO Network: the original scientific basis for its establishment and our R&D vision

OpenAIRE

Winkel, Jørgen; Edwards, Kasper; Dellve, L.; Schiller, B.; Westgaard, Rolf H.

2017-01-01

The NOVO network is a Nordic non-governmental professional association whose aims are to foster the scientific progress, knowledge and development of the working environment within Healthcare as an integrated part of production system development. The vision is a “Nordic Model for Sustainable Systems” in the healthcare sector. It was founded in 2006 in Copenhagen and was financially supported by the Nordic Council of Ministers from 2007 to 2015. The motivation to establish the NOVO Network ar...

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study.

Science.gov (United States)

Steihaug, Ole Martin; Gjesdal, Clara Gram; Bogen, Bård; Kristoffersen, Målfrid Holen; Lien, Gunhild; Ranhoff, Anette Hylen

2017-01-01

Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study.

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Ole Martin Steihaug

Full Text Available Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a the feasibility of determining sarcopenia in patients with acute hip fracture, b the prevalence of sarcopenia and c associations of sarcopenia with nutritional status and comorbidities.A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score.Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37% were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR 1.4 per 5 years, 95% confidence interval (CI [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0].Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.

Sarcopenia in patients with hip fracture: A multicenter cross-sectional study

Science.gov (United States)

Gjesdal, Clara Gram; Bogen, Bård; Kristoffersen, Målfrid Holen; Lien, Gunhild; Ranhoff, Anette Hylen

2017-01-01

Background Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. Methods A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. Results Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. Conclusions Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility. PMID:28902873

Genome sequencing of bacteria: sequencing, de novo assembly and rapid analysis using open source tools.

Science.gov (United States)

Kisand, Veljo; Lettieri, Teresa

2013-04-01

De novo genome sequencing of previously uncharacterized microorganisms has the potential to open up new frontiers in microbial genomics by providing insight into both functional capabilities and biodiversity. Until recently, Roche 454 pyrosequencing was the NGS method of choice for de novo assembly because it generates hundreds of thousands of long reads (tools for processing NGS data are increasingly free and open source and are often adopted for both their high quality and role in promoting academic freedom. The error rate of pyrosequencing the Alcanivorax borkumensis genome was such that thousands of insertions and deletions were artificially introduced into the finished genome. Despite a high coverage (~30 fold), it did not allow the reference genome to be fully mapped. Reads from regions with errors had low quality, low coverage, or were missing. The main defect of the reference mapping was the introduction of artificial indels into contigs through lower than 100% consensus and distracting gene calling due to artificial stop codons. No assembler was able to perform de novo assembly comparable to reference mapping. Automated annotation tools performed similarly on reference mapped and de novo draft genomes, and annotated most CDSs in the de novo assembled draft genomes. Free and open source software (FOSS) tools for assembly and annotation of NGS data are being developed rapidly to provide accurate results with less computational effort. Usability is not high priority and these tools currently do not allow the data to be processed without manual intervention. Despite this, genome assemblers now readily assemble medium short reads into long contigs (>97-98% genome coverage). A notable gap in pyrosequencing technology is the quality of base pair calling and conflicting base pairs between single reads at the same nucleotide position. Regardless, using draft whole genomes that are not finished and remain fragmented into tens of contigs allows one to characterize

Spontaneous de novo vaginal adenosis resembling Bartholin’s ...

African Journals Online (AJOL)

Adebayo Alade Adewole

Spontaneous de novo vaginal adenosis resembling Bartholin's cyst: A case report ... 6 by 5 cm. The cervix, uterus, adnexa and Pouch of Douglas (POD) were normal. .... of vaginal cancer.2–4 Although, DES exposed daughters have an.

Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

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Desai Mina

2011-05-01

Full Text Available Abstract Background Small for gestational age (SGA leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR, catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1 and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1 and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

Cardiac 123I-MIBG uptake in de novo Brazilian patients with Parkinson's disease without clinically defined dysautonomia

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Marco Antonio Araujo Leite

2014-06-01

Full Text Available Myocardial scintigraphy with meta-iodo-benzyl-guanidine (123I cMIBG has been studied in Parkinson's disease (PD, especially in Asian countries, but not in Latin America. Most of these studies include individuals with PD associated to a defined dysautonomia. Our goal is to report the cardiac sympathetic neurotransmission in de novo Brazilian patients with sporadic PD, without clinically defined dysautonomia. We evaluated retrospectively a series of 21 consecutive cases with PD without symptoms or signs of dysautonomia assessed by the standard bedside tests. This number was reduced to 14 with the application of exclusion criteria. 123I cMIBG SPECT up-take was low or absent in all of them and the heart/mediastinum ratio was low in 12 of 14. We concluded that 123I cMIBG has been able to identify cardiac sympathetic neurotransmission disorder in Brazilian de novo PD patients without clinically defined dysautonomia.

Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction.

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Choi, Ki Hong; Lee, Ga Yeon; Choi, Jin-Oh; Jeon, Eun-Seok; Lee, Hae-Young; Cho, Hyun-Jai; Lee, Sang Eun; Kim, Min-Seok; Kim, Jae-Joong; Hwang, Kyung-Kuk; Chae, Shung Chull; Baek, Sang Hong; Kang, Seok-Min; Choi, Dong-Ju; Yoo, Byung-Su; Kim, Kye Hun; Park, Hyun-Young; Cho, Myeong-Chan; Oh, Byung-Hee

2018-03-01

There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02). HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted

Evaluation of a multi-atlas based method for segmentation of cardiac CTA data: a large-scale, multicenter, and multivendor study

International Nuclear Information System (INIS)

Kirisli, H. A.; Schaap, M.; Klein, S.; Papadopoulou, S. L.; Bonardi, M.; Chen, C. H.; Weustink, A. C.; Mollet, N. R.; Vonken, E. J.; Geest, R. J. van der; Walsum, T. van; Niessen, W. J.

2010-01-01

Purpose: Computed tomography angiography (CTA) is increasingly used for the diagnosis of coronary artery disease (CAD). However, CTA is not commonly used for the assessment of ventricular and atrial function, although functional information extracted from CTA data is expected to improve the diagnostic value of the examination. In clinical practice, the extraction of ventricular and atrial functional information, such as stroke volume and ejection fraction, requires accurate delineation of cardiac chambers. In this paper, we investigated the accuracy and robustness of cardiac chamber delineation using a multiatlas based segmentation method on multicenter and multivendor CTA data. Methods: A fully automatic multiatlas based method for segmenting the whole heart (i.e., the outer surface of the pericardium) and cardiac chambers from CTA data is presented and evaluated. In the segmentation approach, eight atlas images are registered to a new patient's CTA scan. The eight corresponding manually labeled images are then propagated and combined using a per voxel majority voting procedure, to obtain a cardiac segmentation. Results: The method was evaluated on a multicenter/multivendor database, consisting of (1) a set of 1380 Siemens scans from 795 patients and (2) a set of 60 multivendor scans (Siemens, Philips, and GE) from different patients, acquired in six different institutions worldwide. A leave-one-out 3D quantitative validation was carried out on the eight atlas images; we obtained a mean surface-to-surface error of 0.94±1.12 mm and an average Dice coefficient of 0.93 was achieved. A 2D quantitative evaluation was performed on the 60 multivendor data sets. Here, we observed a mean surface-to-surface error of 1.26±1.25 mm and an average Dice coefficient of 0.91 was achieved. In addition to this quantitative evaluation, a large-scale 2D and 3D qualitative evaluation was performed on 1380 and 140 images, respectively. Experts evaluated that 49% of the 1380 images

Differences in Recurrence Rate and De Novo Incontinence after Endoscopic Treatment of Vesicourethral Stenosis and Bladder Neck Stenosis

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Jennifer Kranz

2017-08-01

Full Text Available ObjectivesThe objective of this study was to compare the recurrence rate and de novo incontinence after endoscopic treatment of vesicourethral stenosis (VUS after radical prostatectomy (RP and for bladder neck stenosis (BNS after transurethral resection of the prostate (TURP.MethodsRetrospective analysis of patients treated endoscopically for VUS after RP or for BNS after TURP at three German tertiary care centers between March 2009 and June 2016. Investigated endpoints were recurrence rate and de novo incontinence. Chi-squared tests and t-tests were used to model the differences between groups.ResultsA total of 147 patients underwent endoscopic therapy for VUS (59.2% or BNS (40.8%. Mean age was 68.3 years (range 44–86, mean follow-up 27.1 months (1–98. Mean time to recurrence after initial therapy was 23.9 months (1–156, mean time to recurrence after prior endoscopic therapy for VUS or BNS was 12.0 months (1–159. Patients treated for VUS underwent significantly more often radiotherapy prior to endoscopic treatment (33.3 vs. 13.3%; p = 0.006 and the recurrence rate was significantly higher (59.8 vs. 41.7%; p = 0.031. The overall success rate of TUR for VUS was 40.2%, success rate of TUR for BNS was 58.3%. TUR for BNS is significantly more successful (p = 0.031. The mean number of TUR for BNS vs. TUR for VUS in successful cases was 1.5 vs. 1.8, which was not significantly different. The rate of de novo incontinence was significantly higher in patients treated for VUS (13.8 vs. 1.7%; p = 0.011. After excluding those patients with radiotherapy prior to endoscopic treatment, the recurrence rate did not differ significantly between both groups (60.3% for VUS vs. 44.2% for BNS; p = 0.091, whereas the rate of de novo incontinence (13.8 for VUS vs. 0% for BNS; p = 0.005 stayed significantly higher in patients treated for VUS.ConclusionMost patients with BNS are successfully treated endoscopically. In patients with

Nutritional Deficiencies in Children of the First 3 Years of Life, According to a Multicenter Study in Ukraine

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S.L. Nyankovsky

2015-04-01

Full Text Available Taking into account the fact that in Ukraine today there is not enough researches that summarize the data on the nutritional status of young children, the prevalence of eating disorders and lack of basic macro- and micronutrients in children, the multicenter study on nutrition of children from 9 months to 3 years of life has been carried out. It was found that the present dietary intake of infants is unbalanced, contains excess energy and proteins, lack of zinc, iron, calcium, and vitamins A, D, E, B6, B12, B1. Due to unbalanced diet, the use of special infant formula instead of unmodified bovine milk in feeding young child can increase consumption of important nutrients (calcium, iron, iodine, vitamin E, D and folates.

Nutritional Deficiencies in Children of the First 3 Years of Life, According to a Multicenter Study in Ukraine

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S.L. Nyankovsky

2013-08-01

Full Text Available Taking into account the fact that in Ukraine today there is not enough researches that summarize the data on the nutritional status of young children, the prevalence of eating disorders and lack of basic macro- and micronutrients in children, the multicenter study on nutrition of children from 9 months to 3 years of life has been carried out. It was found that the present dietary intake of infants is unbalanced, contains excess energy and proteins, lack of zinc, iron, calcium, and vitamins A, D, E, B6, B12, B1. Due to unbalanced diet, the use of special infant formula instead of unmodified bovine milk in feeding young child can increase consumption of important nutrients (calcium, iron, iodine, vitamin E, D and folates.

De Novo Circulating Antidonor's Cell Antibodies During Induced Acute Rejection of Allogeneic Myofibers in Myogenic Cell Transplantation: A Study in Nonhuman Primates

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Daniel Skuk, MD

2017-12-01

Conclusions. Flow cytometry detection of de novo circulating antibodies against the donor’s cells was consistently associated with AR. A clear increase in this antibody detection indicated current or recent AR. Smaller increases in comparison to the preimmunosuppression values were not associated with AR.

CT-based attenuation correction and resolution compensation for I-123 IMP brain SPECT normal database: a multicenter phantom study.

Science.gov (United States)

Inui, Yoshitaka; Ichihara, Takashi; Uno, Masaki; Ishiguro, Masanobu; Ito, Kengo; Kato, Katsuhiko; Sakuma, Hajime; Okazawa, Hidehiko; Toyama, Hiroshi

2018-03-19

Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings. The proposed acquisition and processing protocols were those routinely used at each participating center with additional triple energy window (TEW) scatter correction (SC) and computed tomography (CT) based attenuation correction (CTAC). A multicenter phantom study was conducted on six imaging systems in five centers, with either single photon emission computed tomography (SPECT) or SPECT/CT, and two brain phantoms. The gray/white matter I-123 activity ratio in the brain phantoms was 4, and they were enclosed in either an artificial adult male skull, 1300 Hounsfield units (HU), a female skull, 850 HU, or an acrylic cover. The cut-off frequency of the Butterworth filters was adjusted so that the spatial resolution was unified to a 17.9 mm full width at half maximum (FWHM), that of the lowest resolution system. The gray-to-white matter count ratios were measured from SPECT images and compared with the actual activity ratio. In addition, mean, standard deviation and coefficient of variation images were calculated after normalization and anatomical standardization to evaluate the variability of the NDB. The gray-to-white matter count ratio error without SC and attenuation correction (AC) was significantly larger for higher bone densities (p correction. The proposed protocol showed potential for constructing an appropriate common NDB from SPECT images with SC, AC and spatial resolution compensation.

Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.

Science.gov (United States)

Siciliano, Mattia; De Micco, Rosa; Trojano, Luigi; De Stefano, Manuela; Baiano, Chiara; Passaniti, Carla; De Mase, Antonio; Russo, Antonio; Tedeschi, Gioacchino; Tessitore, Alessandro

2017-08-01

The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages. Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II. Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II. In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI. Copyright © 2017 Elsevier Ltd. All rights reserved.

De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

NARCIS (Netherlands)

Hoischen, Alexander; van Bon, Bregje W. M.; Rodríguez-Santiago, Benjamín; Gilissen, Christian; Vissers, Lisenka E. L. M.; de Vries, Petra; Janssen, Irene; van Lier, Bart; Hastings, Rob; Smithson, Sarah F.; Newbury-Ecob, Ruth; Kjaergaard, Susanne; Goodship, Judith; McGowan, Ruth; Bartholdi, Deborah; Rauch, Anita; Peippo, Maarit; Cobben, Jan M.; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Veltman, Joris A.; Brunner, Han G.; de Vries, Bert B. B. A.

2011-01-01

Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is

An 11bp region with stem formation potential is essential for de novo DNA methylation of the RPS element.

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Matthew Gentry

Full Text Available The initiation of DNA methylation in Arabidopsis is controlled by the RNA-directed DNA methylation (RdDM pathway that uses 24nt siRNAs to recruit de novo methyltransferase DRM2 to the target site. We previously described the REPETITIVE PETUNIA SEQUENCE (RPS fragment that acts as a hot spot for de novo methylation, for which it requires the cooperative activity of all three methyltransferases MET1, CMT3 and DRM2, but not the RdDM pathway. RPS contains two identical 11nt elements in inverted orientation, interrupted by a 18nt spacer, which resembles the features of a stemloop structure. The analysis of deletion/substitution derivatives of this region showed that deletion of one 11nt element RPS is sufficient to eliminate de novo methylation of RPS. In addition, deletion of a 10nt region directly adjacent to one of the 11nt elements, significantly reduced de novo methylation. When both 11nt regions were replaced by two 11nt elements with altered DNA sequence but unchanged inverted repeat homology, DNA methylation was not affected, indicating that de novo methylation was not targeted to a specific DNA sequence element. These data suggest that de novo DNA methylation is attracted by a secondary structure to which the two 11nt elements contribute, and that the adjacent 10nt region influences the stability of this structure. This resembles the recognition of structural features by DNA methyltransferases in animals and suggests that similar mechanisms exist in plants.

Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

Science.gov (United States)

Landry, Steven J.; Farley, Todd; Hoang, Ty

2005-01-01

Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

Modeling ERBB receptor-regulated G1/S transition to find novel targets for de novo trastuzumab resistance

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Thieffry Denis

2009-01-01

Full Text Available Abstract Background In breast cancer, overexpression of the transmembrane tyrosine kinase ERBB2 is an adverse prognostic marker, and occurs in almost 30% of the patients. For therapeutic intervention, ERBB2 is targeted by monoclonal antibody trastuzumab in adjuvant settings; however, de novo resistance to this antibody is still a serious issue, requiring the identification of additional targets to overcome resistance. In this study, we have combined computational simulations, experimental testing of simulation results, and finally reverse engineering of a protein interaction network to define potential therapeutic strategies for de novo trastuzumab resistant breast cancer. Results First, we employed Boolean logic to model regulatory interactions and simulated single and multiple protein loss-of-functions. Then, our simulation results were tested experimentally by producing single and double knockdowns of the network components and measuring their effects on G1/S transition during cell cycle progression. Combinatorial targeting of ERBB2 and EGFR did not affect the response to trastuzumab in de novo resistant cells, which might be due to decoupling of receptor activation and cell cycle progression. Furthermore, examination of c-MYC in resistant as well as in sensitive cell lines, using a specific chemical inhibitor of c-MYC (alone or in combination with trastuzumab, demonstrated that both trastuzumab sensitive and resistant cells responded to c-MYC perturbation. Conclusion In this study, we connected ERBB signaling with G1/S transition of the cell cycle via two major cell signaling pathways and two key transcription factors, to model an interaction network that allows for the identification of novel targets in the treatment of trastuzumab resistant breast cancer. Applying this new strategy, we found that, in contrast to trastuzumab sensitive breast cancer cells, combinatorial targeting of ERBB receptors or of key signaling intermediates does not

De novo and salvage pathway precursor incorporation during DNA replication at the nuclear matrix

International Nuclear Information System (INIS)

Panzeter, P.L.

1988-01-01

Total nuclear DNA can be empirically subdivided into low salt-soluble (LS) DNA (75-80%), high salt-soluble (HS) DNA (18-23%), and nuclear matrix-associated (NM) DNA which remains tightly bound to the nuclear matrix (∼2%). The most-newly replicated DNA is that associated with the nuclear matrix in regenerating rat liver. Analyses of the DNA fractions after various pulse times revealed that the salvage and de novo pathway DNA precursors investigated were incorporated preferentially into NM-DNA at early pulse times, after which the radioactivity became progressively incorporated into HS- and LS-DNA, respectively. These results support two models of nuclear matrix-associated DNA replication, proposed previously, and a third model presented in this dissertation. In addition, the incorporation of de novo pathway precursors lagged significantly (> 10 minutes) behind the incorporation of precursors entering through the salvage pathway. Channeling of salvage pathway precursors to DNA replication sites would explain the more rapid uptake of salvage precursors into NM-DNA than de novo precursors. To investigate the possibility of this heretofore in vitro phenomenon, the incorporation of the salvage precursor, ( 3 H)deoxythymidine, and the de novo precursor, ( 14 C)orotic acid, into NM-DNA and dTTP was examined in regenerating rat liver. There was no significant difference between the incorporation pattern of ( 14 C)orotic acid into NM-DNA thymine and that of ( 14 C)orotic acid into soluble dTTP. Contrastingly, the salvage pathway precursor, ( 3 H)deoxythymidine, labeled NM-DNA before labeling the dTTP pool

Fingolimod Treatment in Relapsing-Remitting Multiple Sclerosis Patients: A Prospective Observational Multicenter Postmarketing Study

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Rocco Totaro

2015-01-01

Full Text Available Objective. The aim of this prospective observational multicenter postmarketing study was to evaluate fingolimod efficacy in a real world clinical setting. Methods. One hundred forty-two subjects with relapsing-remitting multiple sclerosis (RRMS were enrolled in three multiple sclerosis centers throughout Central and Southern Italy between January 2011 and September 2013. After enrollment, regular visits and EDSS assessment were scheduled every 3 months, and MRI scan was obtained every 12 months. Patients were followed up from 1 to 33 months (mean 14.95 ± 9.15 months. The main efficacy endpoints included the proportion of patients free from clinical relapses, from disability progression, from magnetic resonance imaging activity, and from any disease activity. Results. Out of 142 patients enrolled in the study, 88.1% were free from clinical relapse and 69.0% were free from disability progression; 68.5% of patients remained free from new or newly enlarging T2 lesions and 81.7% of patients were free from gadolinium enhancing lesions. Overall the proportion of patients free from any disease activity was 41.9%. Conclusions. Our data in a real world cohort are consistent with previous findings that yield convincing evidence for the efficacy of fingolimod in patients with RRMS.

Data on serologic inflammatory biomarkers assessed using multiplex assays and host characteristics in the Multicenter AIDS Cohort Study (MACS

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Heather S. McKay

2016-12-01

Full Text Available This article contains data on the associations between fixed and modifiable host characteristics and twenty-three biomarkers of inflammation and immune activation measured longitudinally in a cohort of 250 HIV-uninfected men from the Multicenter AIDS Cohort Study (1984–2009 after adjusting for age, study site, and blood draw time of day using generalized gamma regression. This article also presents associations between each biomarker and each host characteristic in a sample restricted to 2001–2009. These data are supplemental to our original research article entitled “Host factors associated with serologic inflammatory markers assessed using multiplex assays” (McKay, S. Heather, Bream, H. Jay, Margolick, B. Joseph, Martínez-Maza, Otoniel, Phair, P. John, Rinaldo, R. Charles, Abraham, G. Alison, L.P. Jacobson, 2016 [1].

Multicenter comparative study of conventional mechanical gas ventilation to tidal liquid ventilation in oleic acid injured sheep.

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Wolfson, Marla R; Hirschl, Ronald B; Jackson, J Craig; Gauvin, France; Foley, David S; Lamm, Wayne J E; Gaughan, John; Shaffer, Thomas H

2008-01-01

We performed a multicenter study to test the hypothesis that tidal liquid ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.

Medical students and controversial ethical issues: results from the multicenter study SBRAME.

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Lucchetti, Giancarlo; de Oliveira, Leandro Romani; Leite, José Roberto; Lucchetti, Alessandra Lamas Granero

2014-12-15

Medical students(MS) will face ethical issues throughout their lives as doctors. The present study aims to investigate medical students' opinions on controversial ethical issues and factors associated with these opinions. SBRAME (Spirituality and Brazilian Medical Education) is a multicenter study involving 12 Brazilian medical schools with 5950 MS. Participants completed a questionnaire that collected information on socio-demographic data, medical schools characteristics, religious beliefs and opinions on controversial ethical issues. Of all MS, 3630 participated in the survey (61.0%). The sample was 53.8% women and the mean age was 22.5 years. In general, most MS have no objections to prescription of birth control (90.8%), adult stem cell use (87.5%), embryonic stem cell use (82.0%) and abortion for genetic reasons (51.2%). Approximately half of students have no objections to human cloning (47.3%), 45.7% to withdrawal of artificial life support, 41.4% to euthanasia and 23.3% to abortion for failed contraception. Socio-demographic data such as age, gender and income had little influence on MS opinions. On the other hand, medical schools characteristics (number of medical students in the university, year of medical school foundation, location of the university and type of university) and religious aspects (religious affiliation, religious attendance, non-organizational religiousness and intrinsic religiousness) were highly correlated with their opinions. In general, MS with more supportive opinions on controversial ethical issues were less religious and from non-traditional (newer), urban, public and bigger universities. The current study reveals MS have different opinions regarding controversial ethical issues. Noteworthy, these opinions seem to be shaped more by university characteristics and religious beliefs than socio-demographic data.

How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study.

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Bémer, Pascale; Léger, Julie; Tandé, Didier; Plouzeau, Chloé; Valentin, Anne Sophie; Jolivet-Gougeon, Anne; Lemarié, Carole; Kempf, Marie; Héry-Arnaud, Geneviève; Bret, Laurent; Juvin, Marie Emmanuelle; Giraudeau, Bruno; Corvec, Stéphane; Burucoa, Christophe

2016-02-01

Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

De novo transcriptome assembly associated with fumonisin production by the rice pathogen Fusarium fujikuroi

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Keerthi S. Guruge

2018-06-01

Full Text Available The present study employed a next-generation sequencing method to assemble a de novo transcriptome database designed to distinguish gene expression changes exhibited by the fumonisin-producing fungus Fusarium fujikuroi when grown under ‘fumonisin-producing’ compared to ‘non-fumonisin-producing’ conditions. The raw data of this study have been deposited at DNA Data Bank of Japan (DDBJ under the accession ID DRA006146. Keywords: Fusarium fujikuroi, Fumonisin, Next-generation sequencing, Transcriptome, Gene-expression

Melhoramento do cafeeiro: XLII. Produtividade de progênies derivadas de hibridação dos cultivares Laurina e Mundo Novo Coffee breeding: XLII. Yield of progenies from crosses of Laurina and Mundo Novo cultivars of Coffea arabica L.

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Alcides Carvalho

1988-01-01

Full Text Available O cultivar Laurina de Coffea arabica L. caracteriza-se pelo pequeno porte, folhas de dimensões reduzidas, frutos afilados na base, sementes pequenas e afiladas, pequeno rendimento e reduzida produção. Apresenta, no entanto, bebida de boa qualidade e baixo teor de cafeína nas sementes. Suas principais características são controladas pela ação de um par de alelos recessivos lrlr, de acentuado efeito pleiotrópico. Devido ao atual interesse do comércio por produto de baixo teor de cafeína, iniciaram-se pesquisas tendo em vista principalmente aumentar a produtividade do 'Laurina'. Para esse fim, realizaram-se numerosas hibridações de cafeeiros do 'Laurina' com os do 'Mundo Novo' (Coffea arabica e, posteriormente, retrocruzamentos com o 'Mundo Novo'. Estudaram-se as progênies F2 e retrocruzamentos com o 'Mundo Novo' (RC em Campinas, em um experimento, anotando-se as produções por oito anos consecutivos. Separaram-se algumas progênies F2 em dois grupos, antes do plantio: normais (LrLr,Lrlr e laurina (Irlr. Como testemunhas, usaram-se progênies do 'Mundo Novo' e 'Catuaí Amarelo' de C. arabica. O conjunto de plantas F2 do grupo laurina e os retrocruzamentos tiveram produção média maior do que as plantas F2 normais, porém menor do que as testemunhas. Alguns retrocruzamentos e progênies F2 apresentaram plantas com razoável produtividade, indicando que, através de retrocruzamentos com o 'Mundo Novo', podem-se obter novos tipos comerciais com as características morfológicas do 'Laurina'. Fizeram-se considerações sobre a melhor capacidade de combinação do 'Laurina' com algumas seleções do 'Mundo Novo'.The Laurina cultivars of Coffea arabica L. has a reduced plant size, small leaves, small and pointed seeds and low yield capacity. However the seeds have a good cup quality and the desirable characteristic of low caffeine content The Laurina phenotype is supposed to be controlled by a pair of recessive alleles lrlr, with

Factors associated with nursing students' academic success or failure: a retrospective Italian multicenter study.

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Dante, A; Valoppi, G; Saiani, L; Palese, A

2011-01-01

With the increasing standardization of nursing education in Europe under the Bologna Process Declaration (1999), there is a growing interest in defining a common concept of academic success and/or failure, measuring associated factors and comparing differences and similarities between different countries. While there is literature available on these issues from other countries, the phenomenon has not been studied in Italy. The aim of this study was to define the factors associated with academic success or failure in an Italian cohort of nursing students on a bachelor's degree course. A retrospective multicenter study design was adopted. All students enrolling in the academic year 2004-05 on two different bachelor's courses in the north of Italy were interviewed. Only 81 of the 117 students considered (69.2%) concluded their course in three years. Multivariate analysis identified two factors determining academic success/failure: good results in the entry examination for the bachelor's degree in nursing sciences were associated with academic success (OR 4.217, IC(95%) 1.501-11.84), while family commitments, e.g. caring for children or elderly people were associated with academic failure (OR 0.120, IC(95%) 0.03-0.471). Academic failure has a strong impact on students, their families, the teaching faculties and the community, and its prevention is a challenge in the countries with a shortage of nurses. Copyright © 2010 Elsevier Ltd. All rights reserved.

Factors associated to depression and anxiety in medical students: a multicenter study

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Fernanda Brenneisen Mayer

2016-10-01

Full Text Available Abstract Background To evaluate personal and institutional factors related to depression and anxiety prevalence of students from 22 Brazilian medical schools. Methods The authors performed a multicenter study (August 2011 to August 2012, examining personal factors (age, sex, housing, tuition scholarship and institutional factors (year of the medical training, school legal status, location and support service in association with scores of Beck Depression Inventory (BDI and State Trait Anxiety Inventory (STAI. Results Of 1,650 randomly selected students, 1,350 (81.8 % completed the study. The depressive symptoms prevalence was 41 % (BDI > 9, state-anxiety 81.7 % and trait-anxiety in 85.6 % (STAI > 33. There was a positive relationship between levels of state (r = 0,591, p < 0.001 and trait (r = 0,718, p < 0.001 anxiety and depression scores. All three symptoms were positively associated with female sex and students from medical schools located in capital cities of both sexes. Tuition scholarship students had higher state-anxiety but not trait-anxiety or depression scores. Medical students with higher levels of depression and anxiety symptoms disagree more than their peers with the statements “I have adequate access to psychological support” and “There is a good support system for students who get stressed”. Conclusions The factors associated with the increase of medical students’ depression and anxiety symptoms were female sex, school location and tuition scholarship. It is interesting that tuition scholarship students showed state-anxiety, but not depression and trait-anxiety symptoms.

Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

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Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

2011-01-01

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

A Multicenter Comparative Study of Impulse Control Disorder in Latin American Patients With Parkinson Disease.

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Ramírez Gómez, Carolina Candelaria; Serrano Dueñas, Marcos; Bernal, Oscar; Araoz, Natalia; Sáenz Farret, Michel; Aldinio, Victoria; Montilla, Verónica; Micheli, Federico

Impulse control disorder (ICD) is a common adverse effect in patients with Parkinson disease who receive dopamine agonists; however, other factors are involved in its manifestations. To study the frequency and factors involved in the development of this adverse effect in a Latin American population, we conducted a cross-sectional multicenter study. Two hundred fifty-five patients in 3 Latin American centers were evaluated by examination and application of scales (Unified Parkinson's Disease Rating Scale, Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale, Hoehn and Yahr, Clinical Impression of Severity Index for Parkinson's Disease). Of the patients, 27.4% had ICD, most of whom were on dopamine agonists. Other associated risk factors included a younger age at onset of Parkinson disease, moderate symptoms, a shorter evolution of the clinical manifestations, rapid eye movement (REM) sleep disorder behavior, and the consumption of tea, mate, and alcohol. The frequency of ICD is higher in Latin America than in Anglo-Saxon populations. Consuming tea and mate, in addition to the use of dopamine agonists, is a factor that may demonstrate a genetic link that predisposes patients to the establishment of an ICD.

Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity: Multicenter Tracer Kinetic Study.

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Borén, Jan; Watts, Gerald F; Adiels, Martin; Söderlund, Sanni; Chan, Dick C; Hakkarainen, Antti; Lundbom, Nina; Matikainen, Niina; Kahri, Juhani; Vergès, Bruno; Barrett, P Hugh R; Taskinen, Marja-Riitta

2015-10-01

Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration. We focused on factors that predict the kinetics of very-low density lipoprotein 1 (VLDL1) triglycerides. A multicenter study using dual stable isotopes (deuterated leucine and glycerol) and multicompartmental modeling was performed to elucidate the kinetics of triglycerides and apoB in VLDL1 in 46 subjects with abdominal obesity and additional cardiometabolic risk factors. Results showed that plasma triglyceride concentrations were dependent on both the secretion rate (r=0.44, Ptriglycerides and VLDL1-apoB. Liver fat mass was independently and directly associated with secretion rates of VLDL1-triglycerides (r=0.56, Ptriglycerides (r=0.48, Ptriglyceride concentrations in abdominal obesity are determined by the kinetics of VLDL1 subspecies, catabolism being mainly dependent on apoC-III concentration and secretion on liver fat content. Reduction in liver fat and targeting apoC-III may be an effective approach for correcting triglyceride metabolism atherogenic dyslipidemia in obesity. © 2015 American Heart Association, Inc.

The QUASAR reproducibility study, Part II: Results from a multi-center Arterial Spin Labeling test-retest study.

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Petersen, Esben Thade; Mouridsen, Kim; Golay, Xavier

2010-01-01

Arterial Spin Labeling (ASL) is a method to measure perfusion using magnetically labeled blood water as an endogenous tracer. Being fully non-invasive, this technique is attractive for longitudinal studies of cerebral blood flow in healthy and diseased individuals, or as a surrogate marker of metabolism. So far, ASL has been restricted mostly to specialist centers due to a generally low SNR of the method and potential issues with user-dependent analysis needed to obtain quantitative measurement of cerebral blood flow (CBF). Here, we evaluated a particular implementation of ASL (called Quantitative STAR labeling of Arterial Regions or QUASAR), a method providing user independent quantification of CBF in a large test-retest study across sites from around the world, dubbed "The QUASAR reproducibility study". Altogether, 28 sites located in Asia, Europe and North America participated and a total of 284 healthy volunteers were scanned. Minimal operator dependence was assured by using an automatic planning tool and its accuracy and potential usefulness in multi-center trials was evaluated as well. Accurate repositioning between sessions was achieved with the automatic planning tool showing mean displacements of 1.87+/-0.95 mm and rotations of 1.56+/-0.66 degrees . Mean gray matter CBF was 47.4+/-7.5 [ml/100 g/min] with a between-subject standard variation SD(b)=5.5 [ml/100 g/min] and a within-subject standard deviation SD(w)=4.7 [ml/100 g/min]. The corresponding repeatability was 13.0 [ml/100 g/min] and was found to be within the range of previous studies.

Identification of optimum sequencing depth especially for de novo genome assembly of small genomes using next generation sequencing data.

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Desai, Aarti; Marwah, Veer Singh; Yadav, Akshay; Jha, Vineet; Dhaygude, Kishor; Bangar, Ujwala; Kulkarni, Vivek; Jere, Abhay

2013-01-01

Next Generation Sequencing (NGS) is a disruptive technology that has found widespread acceptance in the life sciences research community. The high throughput and low cost of sequencing has encouraged researchers to undertake ambitious genomic projects, especially in de novo genome sequencing. Currently, NGS systems generate sequence data as short reads and de novo genome assembly using these short reads is computationally very intensive. Due to lower cost of sequencing and higher throughput, NGS systems now provide the ability to sequence genomes at high depth. However, currently no report is available highlighting the impact of high sequence depth on genome assembly using real data sets and multiple assembly algorithms. Recently, some studies have evaluated the impact of sequence coverage, error rate and average read length on genome assembly using multiple assembly algorithms, however, these evaluations were performed using simulated datasets. One limitation of using simulated datasets is that variables such as error rates, read length and coverage which are known to impact genome assembly are carefully controlled. Hence, this study was undertaken to identify the minimum depth of sequencing required for de novo assembly for different sized genomes using graph based assembly algorithms and real datasets. Illumina reads for E.coli (4.6 MB) S.kudriavzevii (11.18 MB) and C.elegans (100 MB) were assembled using SOAPdenovo, Velvet, ABySS, Meraculous and IDBA-UD. Our analysis shows that 50X is the optimum read depth for assembling these genomes using all assemblers except Meraculous which requires 100X read depth. Moreover, our analysis shows that de novo assembly from 50X read data requires only 6-40 GB RAM depending on the genome size and assembly algorithm used. We believe that this information can be extremely valuable for researchers in designing experiments and multiplexing which will enable optimum utilization of sequencing as well as analysis resources.

Health care utilization in patients with gout: a prospective multicenter cohort study.

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Singh, Jasvinder A; Bharat, Aseem; Khanna, Dinesh; Aquino-Beaton, Cleopatra; Persselin, Jay E; Duffy, Erin; Elashoff, David; Khanna, Puja P

2017-05-31

All published studies of health care utilization in gout have been cross-sectional to date, and most used a patient-reported diagnosis of gout. Our objective was to assess health care utilization and its predictors in patients with physician-confirmed gout in a prospective cohort study. In a multi-center prospective cohort study of U.S. veterans with rheumatologist-confirmed gout (N = 186; two centers), we assessed patient self-reported overall and gout-specific health care utilization with the Gout Assessment Questionnaire (GAQ) every 3-months for a 9-month period. Comparisons were made using the student's t test or the chi-square, Wilcoxon rank sum test or Fisher exact test, as appropriate. Mixed effects Poisson regression was used to assess potential correlates of gout-related health care utilization. Mean age was 64.6 years, 98% were men, 13% Hispanic or Latino, 32% were African-American, 6% did not graduate high school, mean serum urate was 8.3 and mean Deyo-Charlson score was 3.1. During the past year, mean gout-related visits were as follows: rheumatologist, 1.5; primary care physician, 2 visits; ≥1 inpatient visits, 7%; ≥1 ER visits, 26%; and urgent care/walk-in visit, 33%. In longitudinal analyses, African-American race and gout flares in the last 3 months were associated with significantly higher rate ratio of gout-related outpatient visits. African-American race and lack of college education were associated with significantly higher rate ratio for gout-related urgent visits and overnight stays. African-American race and recent gout flares were associated with higher outpatient utilization and African-American race and no college education with higher urgent or inpatient utilization. Future studies should examine whether modifiable predictors of utilization can be targeted to reduce healthcare utilization in patients with gout.

De Novo Advanced Adult-Onset Offending: New Evidence from a Population of Federal Correctional Clients.

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DeLisi, Matt; Tahja, Katherine N; Drury, Alan J; Elbert, Michael J; Caropreso, Daniel E; Heinrichs, Timothy

2018-01-01

Adult antisocial behavior is almost always predated by delinquency during childhood or adolescence; however, there is also evidence of adult-onset criminal offending. This study examined this controversial subgroup of offenders using self-reported and official data from a total population of federal correctional clients selected from the Midwestern United States. Difference of means t-tests, chi-square tests, and logistic regression models found that 11.7% of clients had an adult onset of offending and 2.7% of clients (n = 23) had an onset occurring at age 60 years or older. This group-introduced as de novo advanced adult-onset offenders-had high socioeconomic status, mixed evidence of adverse childhood experiences, and virtually no usage of drugs with the exception of alcohol. These offenders were primarily convicted of social security and white-collar crimes and evinced remarkably low psychopathology and criminal risk. More research is needed to replicate the phenomenon of de novo advanced adult-onset offending. © 2017 American Academy of Forensic Sciences.

NxRepair: error correction in de novo sequence assembly using Nextera mate pairs

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Rebecca R. Murphy

2015-06-01

Full Text Available Scaffolding errors and incorrect repeat disambiguation during de novo assembly can result in large scale misassemblies in draft genomes. Nextera mate pair sequencing data provide additional information to resolve assembly ambiguities during scaffolding. Here, we introduce NxRepair, an open source toolkit for error correction in de novo assemblies that uses Nextera mate pair libraries to identify and correct large-scale errors. We show that NxRepair can identify and correct large scaffolding errors, without use of a reference sequence, resulting in quantitative improvements in the assembly quality. NxRepair can be downloaded from GitHub or PyPI, the Python Package Index; a tutorial and user documentation are also available.

Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

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Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

2016-12-01

: Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

Results of a Peripheral Cutting Balloon Prospective Multicenter European Registry in Hemodialysis Vascular Access

International Nuclear Information System (INIS)

Peregrin, Jan H.; Rocek, Miloslav

2007-01-01

Purpose. To report initial experience with the Peripheral Cutting Balloon (PCB) in treatment of failing hemodialysis shunts. Methods. A total of 190 patients (95 men, 95 women; average age 64.4 ± 11.9 years, range 32-87 years) who were treated with the PCB for pressure-resistant stenosis, restenosis or failed percutaneous transluminal angioplasty (PTA) in the venous limb of an arteriovenous shunt were followed in seven European centers using a simple registry. The group consisted of 109 de novo lesions (57%) and 79 restenotic lesions (43%). Results. Technical success was achieved in 88.9% of cases. Primary patency was as follows (the results for whole group and simultaneous results for de novo lesions and restenoses are presented): 1 month (140 patients followed): 94%, 98%, and 93%; 3 months (116 patients followed): 93%, 98%, and 92%; 6 months (40 patients followed): 85%, 92%, and 79%; 12 months (27 patients followed): 74%, 87%, and 48%. No complication occurred. Patients experienced an equal or lower level of pain during the procedure compared with conventional PTA. Conclusion. The PCB proved to be successful in dilating pressure-resistant stenoses. We cannot conclude whether PCB angioplasty can lower the restenosis rate in hemodialysis access lesions, but the long-term patency for de novo lesions is high. A further randomized study is advisable

Novos encontros de anofelíneos em recipientes artificiais

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Oswaldo Paulo Forattini

1998-12-01

Full Text Available Assinalam-se novos encontros de anofelíneos em recipientes artificiais. Um deles diz respeito a formas imaturas de Anopheles bellator em criadouros experimentais e outro é concernente ao achado de An. albitarsis l.s., em recipiente abandonado. Tecem-se considerações sobre a pressão seletiva representada pela produção, cada vez maior, de objetos descartáveis.

[The tinnitus questionnaire. A standard instrument for grading the degree of tinnitus. Results of a multicenter study with the tinnitus questionnaire].

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Goebel, G; Hiller, W

1994-03-01

The clinical examination of patients with severe and chronic tinnitus must include associated psychological disturbances. The present paper describes traditional diagnostic methods of ENT practice as well as the Tinnitus Questionnaire (TQ) which has been evaluated in a number of studies. This instrument differentiates between emotional and cognitive distress, auditory perceptual difficulties and self-experienced intrusiveness produced by the tinnitus. The results of a German multicenter study are presented which show that the TQ can be used to demonstrate differences of tinnitus distress under different clinical conditions (e.g., ENT clinic vs psychosomatic clinic and in- vs out-patient care). The TQ can be employed for comparative studies in different tinnitus-related institutions and for the evaluation of the relative effects of different treatment approaches.

Building a better fragment library for de novo protein structure prediction.

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Saulo H P de Oliveira

Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

Building a Better Fragment Library for De Novo Protein Structure Prediction

Science.gov (United States)

de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

2015-01-01

Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial.

Science.gov (United States)

Schenkman, Margaret; Moore, Charity G; Kohrt, Wendy M; Hall, Deborah A; Delitto, Anthony; Comella, Cynthia L; Josbeno, Deborah A; Christiansen, Cory L; Berman, Brian D; Kluger, Benzi M; Melanson, Edward L; Jain, Samay; Robichaud, Julie A; Poon, Cynthia; Corcos, Daniel M

2018-02-01

Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise. To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial. The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control). High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months. Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score. A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the

Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence following Transplantation.

Science.gov (United States)

Welling, Theodore H; Eddinger, Kevin; Carrier, Kristen; Zhu, Danting; Kleaveland, Tyler; Moore, Derek E; Schaubel, Douglas E; Abt, Peter L

2018-05-05

Orthotopic liver transplantation (OLT) and resection are effective treatments for hepatocellular carcinoma (HCC). However, optimizing OLT and limiting HCC recurrence remains a vexing problem. New HCC MELD and allocation algorithms provide greater observation of HCC patients, many while receiving local-regional treatments. Potential benefits of local-regional treatment for limiting HCC recurrence post-OLT remain incompletely understood. Therefore we aimed to define HCC specific prognostic factors affecting recurrence in a contemporary, multi-center cohort of HCC patients undergoing OLT and specifically whether local-regional therapies limited recurrence. We identified 441 patients undergoing OLT for HCC at three major transplant centers from 2008-2013. Cox regression was used to analyze covariate-adjusted recurrence and mortality rates post-OLT. "Bridging" or "down-staging" therapy was used in 238 patients (54%) with transarterial chemoembolization (TACE) being used in 170 (71%) of treated patients. The survival rate post-OLT was 88% and 78% at 1 and 3 years, respectively, with HCC recurrence (28% of deaths) significantly increasing mortality rate (HR=19.87, pOLT. Local-regional therapy to achieve a pathologic response (decreasing tumor size) can limit HCC recurrences post-OLT. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Validation of the Spanish version of the Hip Outcome Score: a multicenter study.

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Seijas, Roberto; Sallent, Andrea; Ruiz-Ibán, Miguel Angel; Ares, Oscar; Marín-Peña, Oliver; Cuéllar, Ricardo; Muriel, Alfonso

2014-05-13

The Hip Outcome Score (HOS) is a self-reported questionnaire evaluating the outcomes of treatment interventions for hip pathologies, divided in 19 items of activities of daily life (ADL) and 9 sports' items. The aim of the present study is to translate and validate HOS into Spanish. A prospective and multicenter study with 100 patients undergoing hip arthroscopy was performed between June 2012 and January 2013. Crosscultural adaptation was used to translate HOS into Spanish. Patients completed the questionnaire before and after surgery. Feasibility, reliability, internal consistency, construct validity (correlation with Western Ontario and McMaster Universities Osteoarthritis Index), ceiling and floor effects and sensitivity to change were assessed for the present study. Mean age was 45.05 years old. 36 women and 64 men were included. Feasibility: 13% had at least one missing item within the ADL subscale and 17% within the sport subscale. Reliability: the translated version of HOS was highly reproducible with intraclass correlation coefficient of 0.95 for ADL and 0.94 for the sports subscale. Internal consistency was confirmed with Cronbach's alpha >0.90 in both subscales. Construct validity showed statistically significant correlation with WOMAC. Ceiling effect was observed in 6% and 12% for ADL and sports subscale, respectively. Floor effect was found in 3% and 37% ADL and sports subscale, respectively. Large sensitivity to change was shown in both subscales. The translated version of HOS into Spanish has shown to be feasible, reliable and sensible to changes for patients undergoing hip arthroscopy. This validated translation of HOS allows for comparisons between studies involving either Spanish- or English-speaking patients. Prognostic study, Level I.

Carotid Artery Injury in Anterior Cervical Spine Surgery: Multicenter Cohort Study and Literature Review.

Science.gov (United States)

Härtl, Roger; Alimi, Marjan; Abdelatif Boukebir, Mohamed; Berlin, Connor D; Navarro-Ramirez, Rodrigo; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel

2017-04-01

Retrospective study and literature review. To provide more comprehensive data about carotid artery injury (CAI) or cerebrovascular accident (CVA) related to anterior cervical spine surgery. We conducted a retrospective, multicenter, case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network. Medical records of 17 625 patients who went through cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were analyzed. Also, we performed a literature review using Medline and PubMed databases. The following terms were used alone, and in combination, to search for relevant articles: cervical, spine, surgery, complication, iatrogenic, carotid artery, injury, cerebrovascular accident, CVA, and carotid stenosis. Among 17 625 patients that were analyzed, no cases were reported to experienced CAI or CVA after cervical spine surgery. Nevertheless, in our PubMed search we found 157 articles, but only 5 articles matched our study objective criteria; 2 cases were reported to present CAI and 3 cases presented CVA. CAI and CVA related to anterior cervical spine surgeries are extremely rare. We were not able to find neither in our retrospective study nor in our literature research a correlation between the type or length of anterior cervical spine procedure with CVA or CAI complications. However, surgeons should be aware of the possibility of vascular complications and minimize intraoperative direct vascular manipulations or retraction. Preoperative screening for underlying vascular pathology and risk factors is also important.

A multicenter qualitative study on preventing hospital-acquired urinary tract infection in US hospitals.

Science.gov (United States)

Saint, Sanjay; Kowalski, Christine P; Forman, Jane; Damschroder, Laura; Hofer, Timothy P; Kaufman, Samuel R; Creswell, John W; Krein, Sarah L

2008-04-01

Although urinary tract infection (UTI) is the most common hospital-acquired infection, there is little information about why hospitals use or do not use a range of available preventive practices. We thus conducted a multicenter study to understand better how US hospitals approach the prevention of hospital-acquired UTI. This research is part of a larger study employing both quantitative and qualitative methods. The qualitative phase consisted of 38 semistructured phone interviews with key personnel at 14 purposefully sampled US hospitals and 39 in-person interviews at 5 of those 14 hospitals, to identify recurrent and unifying themes that characterize how hospitals have addressed hospital-acquired UTI. Four recurrent themes emerged from our study data. First, although preventing hospital-acquired UTI was a low priority for most hospitals, there was substantial recognition of the value of early removal of a urinary catheter for patients. Second, those hospitals that made UTI prevention a high priority also focused on noninfectious complications and had committed advocates, or "champions," who facilitated prevention activities. Third, hospital-specific pilot studies were important in deciding whether or not to use devices such as antimicrobial-impregnated catheters. Finally, external forces, such as public reporting, influenced UTI surveillance and infection prevention activities. Clinicians and policy makers can use our findings to develop initiatives that, for example, use a champion to promote the removal of unnecessary urinary catheters or exploit external forces, such public reporting, to enhance patient safety.

De novo post-pollen mitosis II tobacco pollen tube transcriptome

Czech Academy of Sciences Publication Activity Database

Hafidh, Said; Breznenová, Katarína; Honys, David

2012-01-01

Roč. 7, č. 8 (2012), s. 918-921 ISSN 1559-2316 R&D Projects: GA ČR GPP501/11/P321; GA ČR GA522/09/0858 Institutional research plan: CEZ:AV0Z50380511 Keywords : de novo pollen tube transcriptome * male gametophyte development * pollen tube growth Subject RIV: ED - Physiology

Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting.

Directory of Open Access Journals (Sweden)

Shannon M Lynch

Full Text Available Leukocyte telomere length(LTL has been associated with age, self-reported race/ethnicity, gender, education, and psychosocial factors, including perceived stress, and depression. However, inconsistencies in associations of LTL with disease and other phenotypes exist across studies. Population characteristics, including race/ethnicity, laboratory methods, and statistical approaches in LTL have not been comprehensively studied and could explain inconsistent LTL associations.LTL was measured using Southern Blot in 1510 participants from a multi-ethnic, multi-center study combining data from 3 centers with different population characteristics and laboratory processing methods. Main associations between LTL and psychosocial factors and LTL and race/ethnicity were evaluated and then compared across generalized estimating equations(GEE and linear regression models. Statistical models were adjusted for factors typically associated with LTL(age, gender, cancer status and also accounted for factors related to center differences, including laboratory methods(i.e., DNA extraction. Associations between LTL and psychosocial factors were also evaluated within race/ethnicity subgroups (Non-hispanic Whites, African Americans, and Hispanics.Beyond adjustment for age, gender, and cancer status, additional adjustments for DNA extraction and clustering by center were needed given their effects on LTL measurements. In adjusted GEE models, longer LTL was associated with African American race (Beta(β(standard error(SE = 0.09(0.04, p-value = 0.04 and Hispanic ethnicity (β(SE = 0.06(0.01, p-value = 0.02 compared to Non-Hispanic Whites. Longer LTL was also associated with less than a high school education compared to having greater than a high school education (β(SE = 0.06(0.02, p-value = 0.04. LTL was inversely related to perceived stress (β(SE = -0.02(0.003, p<0.001. In subgroup analyses, there was a negative association with LTL in African Americans with a high

The Experience of Surrogate Decision Makers on Being Approached for Consent for Patient Participation in Research. A Multicenter Study.

Science.gov (United States)

Burns, Karen E A; Prats, Clara Juando; Maione, Maria; Lanceta, Mary; Zubrinich, Celia; Jeffs, Lianne; Smith, Orla M

2017-02-01

Recruitment in critical care research differs from other contexts in important ways: patients lack decision-making capacity, uncertainty exists regarding patient prognosis, and critical illnesses are often associated with appreciable morbidity and mortality. We aimed to describe the experiences of surrogate decision makers (SDMs) in being approached for consent for critically ill patients to participate in research. A multicenter, qualitative study involving semistructured interviews with 26 SDMs, who provided or declined surrogate consent for research participation, at 5 Canadian centers nested within a multicenter observational study of research recruitment practices. Transcripts were reviewed by three qualitative researchers, and data were analyzed using grounded theory and a narrative critical analysis. SDMs were guided by an overarching desire for the patient to live. Surrogate research decision-making involved three sequential stages: (1) being approached; (2) reflecting on participation; and (3) making a decision. In stage 1, SDMs identified factors (their expectations, how they were approached, the attributes of the person approaching, and study risks and benefits) that characterized their consent encounter and affirmed a preference to be approached in person. If SDMs perceived the risk of participation to be too high or felt patients may not benefit from participation, they did not contemplate further. In stage 2, SDMs who knew the patient's wishes or had a deeper understanding of research prioritized the patient's wishes and the perceived benefits of participation. Without this information, SDMs prioritized obtaining more and better care for the patient, considered what was in their mutual best interests, and valued healthcare professional's knowledge. Trust in healthcare professionals was essential to proceeding further. In stage 3, SDMs considered six factors in rendering decisions. SDMs engaged in three sequential stages and considered six factors in

The de novo assembly of mitochondrial genomes of the extinct passenger pigeon (Ectopistes migratorius with next generation sequencing.

Directory of Open Access Journals (Sweden)

Chih-Ming Hung

Full Text Available The information from ancient DNA (aDNA provides an unparalleled opportunity to infer phylogenetic relationships and population history of extinct species and to investigate genetic evolution directly. However, the degraded and fragmented nature of aDNA has posed technical challenges for studies based on conventional PCR amplification. In this study, we present an approach based on next generation sequencing to efficiently sequence the complete mitochondrial genome (mitogenome of two extinct passenger pigeons (Ectopistes migratorius using de novo assembly of massive short (90 bp, paired-end or single-end reads. Although varying levels of human contamination and low levels of postmortem nucleotide lesion were observed, they did not impact sequencing accuracy. Our results demonstrated that the de novo assembly of shotgun sequence reads could be a potent approach to sequence mitogenomes, and offered an efficient way to infer evolutionary history of extinct species.

The De Novo Assembly of Mitochondrial Genomes of the Extinct Passenger Pigeon (Ectopistes migratorius) with Next Generation Sequencing

Science.gov (United States)

Hung, Chih-Ming; Lin, Rong-Chien; Chu, Jui-Hua; Yeh, Chia-Fen; Yao, Chiou-Ju; Li, Shou-Hsien

2013-01-01

The information from ancient DNA (aDNA) provides an unparalleled opportunity to infer phylogenetic relationships and population history of extinct species and to investigate genetic evolution directly. However, the degraded and fragmented nature of aDNA has posed technical challenges for studies based on conventional PCR amplification. In this study, we present an approach based on next generation sequencing to efficiently sequence the complete mitochondrial genome (mitogenome) of two extinct passenger pigeons (Ectopistes migratorius) using de novo assembly of massive short (90 bp), paired-end or single-end reads. Although varying levels of human contamination and low levels of postmortem nucleotide lesion were observed, they did not impact sequencing accuracy. Our results demonstrated that the de novo assembly of shotgun sequence reads could be a potent approach to sequence mitogenomes, and offered an efficient way to infer evolutionary history of extinct species. PMID:23437111

Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

Directory of Open Access Journals (Sweden)

Borba HHL

2017-01-01

Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

European multicenter study on melanoma immunoscintigraphy by means of 99mTc-labelled monoclonal antibody fragments

International Nuclear Information System (INIS)

Siccardi, A.G.; Viale, G.; Natali, P.G.; Scassellati, G.A.; Ferrone, S.

1990-01-01

A total of 493 melanoma patients were investigated by 20 European nuclear medicine departments by means of the same 99m Tc-labelled immunoradiopharmaceutical and the same immunoscintigraphy (ISG) protocol. (i) No chemical or clinical toxicity was detected during or following the studies. (ii) Positive results were obtained in 287/363 (79%) patients (321 carrying known lesions and 42 carrying previously occult lesions): In 231 (80%) of them, 402/402 lesions were imaged; in the remaining 56 ISG-positive patients, 108/204 lesions were imaged; in 76 patients 0/122 lesions were imaged. (iii) The fraction of melanoma lesions visualized by ISG was 510/728 (70.1%); 605 of these lesions were already documented at the time of the study, and 123 were previously occult. (iv) A total of 218 documented melanoma lesions (30%) were not visualized by ISG in 132 patients: About 70% of the ISG-negative lesions were of small size (less than 2 cm diameter). (v) The melanoma nature of 69/123 previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The results obtained in this study are similar to those obtained in the Italian Multicenter Study which had previously been carried out with 258 melanoma patients. (orig.)

Cost-effectiveness of healthy eating and/or physical activity promotion in pregnant women at increased risk of gestational diabetes mellitus : Economic evaluation alongside the DALI study, a European multicenter randomized controlled trial

NARCIS (Netherlands)

Broekhuizen, K. (Karen); D. Simmons (David); R. Devlieger (Roland); A. Van Assche (Andre); G. Jans (Goele); S. Galjaard (Sander); R. Corcoy (Rosa); J.M. Adelantado (Juan M); F. Dunne (Fidelma); G. Desoye (Gernot); J. Harreiter (Jurgen); A. Kautzky-Willer (Alexandra); P. Damm (Peter); E.R. Mathiesen (Elisabeth); D.M. Jensen (Dorte M.); L. Andersen (Liselotte); A. Lapolla (Annunziata); M.G. Dalfra (Maria G.); A. Bertolotto (Alessandra); E. Wender-Ozegowska (Ewa); A. Zawiejska (Agnieszka); D.J. Hill (David); F.J. Snoek (Frank); J.G.M. Jelsma (Judith G. M.); J.E. Bosmans (Judith); M.N. van Poppel (Mireille); van Dongen, J.M. (Johanna M.)

2018-01-01

markdownabstract__Background:__ Gestational diabetes mellitus (GDM) is associated with perinatal health risks to both mother and offspring, and represents a large economic burden. The DALI study is a multicenter randomized controlled trial, undertaken to add to the knowledge base on the

Developing de novo human artificial chromosomes in embryonic stem cells using HSV-1 amplicon technology.

Science.gov (United States)

Moralli, Daniela; Monaco, Zoia L

2015-02-01

De novo artificial chromosomes expressing genes have been generated in human embryonic stem cells (hESc) and are maintained following differentiation into other cell types. Human artificial chromosomes (HAC) are small, functional, extrachromosomal elements, which behave as normal chromosomes in human cells. De novo HAC are generated following delivery of alpha satellite DNA into target cells. HAC are characterized by high levels of mitotic stability and are used as models to study centromere formation and chromosome organisation. They are successful and effective as gene expression vectors since they remain autonomous and can accommodate larger genes and regulatory regions for long-term expression studies in cells unlike other viral gene delivery vectors currently used. Transferring the essential DNA sequences for HAC formation intact across the cell membrane has been challenging for a number of years. A highly efficient delivery system based on HSV-1 amplicons has been used to target DNA directly to the ES cell nucleus and HAC stably generated in human embryonic stem cells (hESc) at high frequency. HAC were detected using an improved protocol for hESc chromosome harvesting, which consistently produced high-quality metaphase spreads that could routinely detect HAC in hESc. In tumour cells, the input DNA often integrated in the host chromosomes, but in the host ES genome, it remained intact. The hESc containing the HAC formed embryoid bodies, generated teratoma in mice, and differentiated into neuronal cells where the HAC were maintained. The HAC structure and chromatin composition was similar to the endogenous hESc chromosomes. This review will discuss the technological advances in HAC vector delivery using HSV-1 amplicons and the improvements in the identification of de novo HAC in hESc.

An Angiopoietin-2 gene polymorphism in unexplained intrauterine fetal death: a multi-center study.

Science.gov (United States)

Huber, Ambros; Grimm, Christoph; Pietrowski, Detlef; Zeillinger, Robert; Bettendorf, Hertha; Husslein, Peter; Hefler, Lukas

2005-02-01

Angiopoietin-2 (Ang-2) is a potent regulator of angiogenesis and vascular tone. As vascular processes have been proposed to be involved in the pathogenesis of pregnancy associated complications such as late unexplained intrauterine fetal death (IUFD), we determined whether a common G/A polymorphism of the Ang-2 gene (ANGPT2) is associated with this condition. In a multicenter case-control study, we evaluated the common G/A polymorphism within exon 4 of the ANGPT2 gene using PCR in 90 women with IUFD and 90 healthy women with at least one uncomplicated full term pregnancy and no history of IUFD. Genotype (p=0.2; OR=1.4 [0.8-2.6]) and allele frequencies (p=0.1; OR=1.4 [0.9-2.1]) of the ANGPT2 polymorphism did not differ between women with IUFD and healthy women. A multivariate regression analysis with smoking habits and preexisting diabetes as covariates did not change the results. We are the first to report on a common polymorphism of the ANGPT2 gene in patients with late IUFD. The investigated ANGPT2 poylmorphism does not seem to be a candidate gene for IUFD in Caucasian women.

Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

DEFF Research Database (Denmark)

Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

2007-01-01

Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...... at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein...

Desire to Have Children Among Transgender People in Germany: A Cross-Sectional Multi-Center Study.

Science.gov (United States)

Auer, Matthias K; Fuss, Johannes; Nieder, Timo O; Briken, Peer; Biedermann, Sarah V; Stalla, Günter K; Beckmann, Matthias W; Hildebrandt, Thomas

2018-05-01

Many trans individuals undergo medical interventions that result in irreversible loss of fertility. Little is known about their desire to have children and attitudes toward fertility preservation options. To study how the desire for children and the use of fertility preservation options varies among trans women and trans men in different transitioning stages in Germany. In this cross-sectional multi-center study, N = 99 trans women and N = 90 trans men were included. Of these, 26 of each sex were just about to start medical treatment. Outcome parameter were the prevalence and determinants of a desire to have children in trans persons. Before treatment, a desire for children was significantly higher in trans men compared to trans women (P = .016). In contrast, in those who had already started treatment, a current desire to have children was equally present in about one fourth of participants of both genders while the interest in having children in the future was significantly higher in trans women (69.9%) than in trans men (46.9%; P = .034). Although 76.1% of trans women and 76.6% of trans men indicated that they had at least thought about preserving germ cells before starting medical transition, only 9.6% of trans women and 3.1% of trans men had put this idea into practice. Most trans men in both groups indicated that insemination of a female partner with sperm from an unrelated donor was a suitable option to fulfill their child wish, potentially explaining their low interest in preserving their own germ cells. Finally, a logistic regression analysis accounting for potential confounders revealed that overall trans women were more than twice as likely to have a current desire to have children (odds ratio 2.58), and this wish was on average 5.3% lower with each year of increasing age. A low level of fertility preservation among trans persons is contrasted by a high level of desire for children. This highlights the importance of counseling trans individuals

Air contamination for predicting wound contamination in clean surgery: A large multicenter study.

Science.gov (United States)

Birgand, Gabriel; Toupet, Gaëlle; Rukly, Stephane; Antoniotti, Gilles; Deschamps, Marie-Noelle; Lepelletier, Didier; Pornet, Carole; Stern, Jean Baptiste; Vandamme, Yves-Marie; van der Mee-Marquet, Nathalie; Timsit, Jean-François; Lucet, Jean-Christophe

2015-05-01

The best method to quantify air contamination in the operating room (OR) is debated, and studies in the field are controversial. We assessed the correlation between 2 types of air sampling and wound contaminations before closing and the factors affecting air contamination. This multicenter observational study included 13 ORs of cardiac and orthopedic surgery in 10 health care facilities. For each surgical procedure, 3 microbiologic air counts, 3 particles counts of 0.3, 0.5, and 5 μm particles, and 1 bacteriologic sample of the wound before skin closure were performed. We collected data on surgical procedures and environmental characteristics. Of 180 particle counts during 60 procedures, the median log10 of 0.3, 0.5, and 5 μm particles was 7 (interquartile range [IQR], 6.2-7.9), 6.1 (IQR, 5.4-7), and 4.6 (IQR, 0-5.2), respectively. Of 180 air samples, 50 (28%) were sterile, 90 (50%) had 1-10 colony forming units (CFU)/m(3) and 40 (22%) >10 CFU/m(3). In orthopedic and cardiac surgery, wound cultures at closure were sterile for 24 and 9 patients, 10 and 11 had 1-10 CFU/100 cm(2), and 0 and 6 had >10 CFU/100 cm(2), respectively (P air microbial counts (P contamination (P = .22). This study suggests that particle counting is a good surrogate of airborne microbiologic contamination in the OR. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Determinants of Severity in Acute Pancreatitis: A Nation-wide Multicenter Prospective Cohort Study.

Science.gov (United States)

Sternby, Hanna; Bolado, Federico; Canaval-Zuleta, Héctor J; Marra-López, Carlos; Hernando-Alonso, Ana I; Del-Val-Antoñana, Adolfo; García-Rayado, Guillermo; Rivera-Irigoin, Robin; Grau-García, Francisco J; Oms, Lluís; Millastre-Bocos, Judith; Pascual-Moreno, Isabel; Martínez-Ares, David; Rodríguez-Oballe, Juan A; López-Serrano, Antonio; Ruiz-Rebollo, María L; Viejo-Almanzor, Alejandro; González-de-la-Higuera, Belén; Orive-Calzada, Aitor; Gómez-Anta, Ignacio; Pamies-Guilabert, José; Fernández-Gutiérrez-Del-Álamo, Fátima; Iranzo-González-Cruz, Isabel; Pérez-Muñante, Mónica E; Esteba, María D; Pardillos-Tomé, Ana; Zapater, Pedro; de-Madaria, Enrique

2018-04-18

The aim of this study was to compare and validate the different classifications of severity in acute pancreatitis (AP) and to investigate which characteristics of the disease are associated with worse outcomes. AP is a heterogeneous disease, ranging from uneventful cases to patients with considerable morbidity and high mortality rates. Severity classifications based on legitimate determinants of severity are important to correctly describe the course of disease. A prospective multicenter cohort study involving patients with AP from 23 hospitals in Spain. The Atlanta Classification (AC), Revised Atlanta Classification (RAC), and Determinant-based Classification (DBC) were compared. Binary logistic multivariate analysis was performed to investigate independent determinants of severity. A total of 1655 patients were included; 70 patients (4.2%) died. RAC and DBC were equally superior to AC for describing the clinical course of AP. Although any kind of organ failure was associated with increased morbidity and mortality, persistent organ failure (POF) was the most significant determinant of severity. All local complications were associated with worse outcomes. Infected pancreatic necrosis correlated with high morbidity, but in the presence of POF, it was not associated to higher mortality when compared with sterile necrotizing pancreatitis. Exacerbation of previous comorbidity was associated with increased morbidity and mortality. The RAC and DBC both signify an advance in the description and differentiation of AP patients. Herein, we describe the complications of the disease independently associated to morbidity and mortality. Our findings are valuable not only when designing future studies on AP but also for the improvement of current classifications.

De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

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Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

2018-05-08

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

Norgal: extraction and de novo assembly of mitochondrial DNA from whole-genome sequencing data.

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Al-Nakeeb, Kosai; Petersen, Thomas Nordahl; Sicheritz-Pontén, Thomas

2017-11-21

Whole-genome sequencing (WGS) projects provide short read nucleotide sequences from nuclear and possibly organelle DNA depending on the source of origin. Mitochondrial DNA is present in animals and fungi, while plants contain DNA from both mitochondria and chloroplasts. Current techniques for separating organelle reads from nuclear reads in WGS data require full reference or partial seed sequences for assembling. Norgal (de Novo ORGAneLle extractor) avoids this requirement by identifying a high frequency subset of k-mers that are predominantly of mitochondrial origin and performing a de novo assembly on a subset of reads that contains these k-mers. The method was applied to WGS data from a panda, brown algae seaweed, butterfly and filamentous fungus. We were able to extract full circular mitochondrial genomes and obtained sequence identities to the reference sequences in the range from 98.5 to 99.5%. We also assembled the chloroplasts of grape vines and cucumbers using Norgal together with seed-based de novo assemblers. Norgal is a pipeline that can extract and assemble full or partial mitochondrial and chloroplast genomes from WGS short reads without prior knowledge. The program is available at: https://bitbucket.org/kosaidtu/norgal .

Contribution of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic to de novo presentations of heart disease in the Heart of Soweto Study cohort.

Science.gov (United States)

Sliwa, Karen; Carrington, Melinda J; Becker, Anthony; Thienemann, Friedrich; Ntsekhe, Mpiko; Stewart, Simon

2012-04-01

The contemporary impact of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic on heart disease in South Africa (>5 million people affected) is unknown. The Heart of Soweto Study provides a unique opportunity to identify the contribution of cardiac manifestations of this epidemic to de novo presentations of heart disease in an urban African community in epidemiological transition. Chris Hani Baragwanath Hospital services the >1 million people living in Soweto, South Africa. A prospective, clinical registry captured data from all de novo cases of heart disease presenting to the Cardiology Unit during 2006-08. We describe all cases where HIV/AIDS was concurrently diagnosed. Overall, 518 of 5328 de novo cases of heart disease were identified as HIV-positive (9.7%) with 54% of these prescribed highly active anti-retroviral therapies on presentation. Women (62%) and Africans (97%) predominated with women being significantly younger than men 38 ± 13 vs. 42 ± 13 years (P = 0.002). The most common primary diagnosis attributable to HIV/AIDS was HIV-related cardiomyopathy (196 cases, 38%); being prescribed more anti-retroviral therapy (127/196 vs. 147/322; odds ratio 2.85, 95% confidence interval 1.81-3.88) with higher viral loads [median 110 000 (inter-quartile range 26 000-510 000) vs. 19 000 (3200-87 000); P = 0.018] and a lower CD4 count [median 180 (71-315) vs. 211 (96-391); P = 0.019] than the rest. An additional 128 cases (25%) were diagnosed with pericarditis/pericardial effusion with a range of other concurrent diagnoses evident, including 42 cases (8.1%) of HIV-related pulmonary arterial hypertension. Only 14 of all 581 cases of coronary artery disease (CAD) (2.4%, mean age 41 ± 13 years) were confirmed HIV-positive. Cardiac manifestations of HIV/AIDS identified within this cohort were relatively infrequent. While HIV-related cardiomyopathy and pericardial disease remain important targets for early detection and treatment in

Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

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Brzheskiy, Vladimir V; Efimova, Elena L; Vorontsova, Tatiana N; Alekseev, Vladimir N; Gusarevich, Olga G; Shaidurova, Ksenia N; Ryabtseva, Alla A; Andryukhina, Olga M; Kamenskikh, Tatiana G; Sumarokova, Elena S; Miljudin, Eugeny S; Egorov, Eugeny A; Lebedev, Oleg I; Surov, Alexander V; Korol, Andrii R; Nasinnyk, Illia O; Bezditko, Pavel A; Muzhychuk, Olena P; Vygodin, Vladimir A; Yani, Elena V; Savchenko, Alla Y; Karger, Elena M; Fedorkin, Oleg N; Mironov, Alexander N; Ostapenko, Victoria; Popeko, Natalia A; Skulachev, Vladimir P; Skulachev, Maxim V

2015-12-01

This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient. In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated. This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed. Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage. Mitotech LLC.

De novo origin of VCY2 from autosome to Y-transposed amplicon.

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Peng-Rong Cao

Full Text Available The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y

Effectiveness of Psychosocial Interventions in Complex Palliative Care Patients: A Quasi-Experimental, Prospective Multicenter Study.

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Mateo-Ortega, Dolors; Gómez-Batiste, Xavier; Maté, Jorge; Beas, Elba; Ela, Sara; Lasmarias, Cristina; Limonero, Joaquín T

2018-03-13

To determine whether specific psychosocial interventions can ease discomfort in palliative care (PC) patients, particularly in those with high levels of pain or emotional distress. Changes in the psychological parameters of 8333 patients were assessed in a quasi-experimental, prospective, multicenter, single group pretest/post-test study. Psychosocial care was delivered by 29 psychosocial care teams (PSTs; 137 professionals). Pre- and post-intervention changes in these variables were assessed: mood, anxiety, and emotional distress. Patients were classified as complex, when presented with high levels of anxiety, mood, suffering (or perception of time as slow), and distress (or unease, or discomfort), or noncomplex. These groups were compared to assess changes in suffering-related parameters from baseline. Psychosocial interventions reduced patients' suffering. These interventions were more effective in complex patients. After successive psychosocial interventions, the level of suffering in complex patients decreased until close to parity with noncomplex patients, suggesting that patients with major complexity could benefit most from specific psychosocial treatment. These findings support the importance of assessing and treating patients' psychosocial needs.

Novos liberalismos e a Grande Recessão: princípios para uma política externa crítica

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Igor Abdalla

2014-06-01

Full Text Available O artigo analisa a emergência, nas últimas décadas, de novo liberalismo internacionalista de cunho tecnocrático, que se divorcia do liberalismo clássico criado pelo filósofo crítico Immanuel Kant. O novo liberalismo, que coincide com o processo de globalização das finanças, inverte o elemento emancipatório do liberalismo kantiano para apresentar-se como instância de ratificação do poder. Como resultado, os novos liberais são incapazes de analisar criticamente eventos como a Grande Recessão. Em contraposição ao novo liberalismo tecnocrático propõem-se princípios para uma política externa crítica para o Brasil. Em termos empíricos, escrutina-se a evolução do processo de globalização das finanças do ponto de vista do poder, com enfoque sobre as crises financeiras no mundo em desenvolvimento e a Grande Recessão de 2008. Propugnam-se os seguintes argumentos: (i o novo liberalismo contradiz o liberalismo clássico; (ii o novo liberalismo legitima interesses de atores hegemônicos voltados para a liberalização e a desregulamentação financeiras sem limites, que se encontram na raiz da Grande Recessão; (iii a política externa brasileira deve resgatar elementos do liberalismo clássico no contexto de crise gerado pela Grande Recessão.

Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

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Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

2015-05-01

The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-read sequencing and de novo assembly of a Chinese genome

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Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arr...

De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly.

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Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

2015-11-26

Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

Tug-of-war between classical and multicenter bonds in H-(Be)n-H species

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Lundell, Katie A.; Boldyrev, Alexander I.

2018-05-01

Quantum chemical calculations were performed for beryllium homocatenated compounds [H-(Be)n-H]. Global minimum structures were found using machine searches (Coalescence Kick method) with density functional theory. Chemical bonding analysis was performed with the Adaptive Natural Density Partitioning method. It was found that H-(Be)2-H and H-(Be)3-H clusters are linear with classical two-center two-electron bonds, while for n > 3, three-dimensional structures are more stable with multicenter bonding. Thus, at n = 4, multicenter bonding wins the tug-of-war vs. the classical bonding.

Cinema utópico: a construção de um novo homem e um novo mundo

OpenAIRE

Erika Savernini Lopes

2011-01-01

O cinema, desde seus primórdios, prefigurou o espaço cibernético como um novo espaço imaterial construído coletivamente. A concepção desse outro lugar não físico para o qual o homem poderia migrar estabelece para o cinema e para o ciberespaço uma relação direta com as utopias. Na acepção do romance filosófico de Thomas More, a Utopia define-se como um outro espaço não-existente, irrealizável e ideal que diagnostica o atual. O cinema carregaria caracteres fundamentais da Utopia tanto no que se...

Deregulation of S-adenosylmethionine biosynthesis and regeneration improves methylation in the E. coli de novo vanillin biosynthesis pathway.

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Kunjapur, Aditya M; Hyun, Jason C; Prather, Kristala L J

2016-04-11

Vanillin is an industrially valuable molecule that can be produced from simple carbon sources in engineered microorganisms such as Saccharomyces cerevisiae and Escherichia coli. In E. coli, de novo production of vanillin was demonstrated previously as a proof of concept. In this study, a series of data-driven experiments were performed in order to better understand limitations associated with biosynthesis of vanillate, which is the immediate precursor to vanillin. Time-course experiments monitoring production of heterologous metabolites in the E. coli de novo vanillin pathway revealed a bottleneck in conversion of protocatechuate to vanillate. Perturbations in central metabolism intended to increase flux into the heterologous pathway increased average vanillate titers from 132 to 205 mg/L, but protocatechuate remained the dominant heterologous product on a molar basis. SDS-PAGE, in vitro activity measurements, and L-methionine supplementation experiments suggested that the decline in conversion rate was influenced more by limited availability of the co-substrate S-adenosyl-L-methionine (AdoMet or SAM) than by loss of activity of the heterologous O-methyltransferase. The combination of metJ deletion and overexpression of feedback-resistant variants of metA and cysE, which encode enzymes involved in SAM biosynthesis, increased average de novo vanillate titers by an additional 33% (from 205 to 272 mg/L). An orthogonal strategy intended to improve SAM regeneration through overexpression of native mtn and luxS genes resulted in a 25% increase in average de novo vanillate titers (from 205 to 256 mg/L). Vanillate production improved further upon supplementation with methionine (as high as 419 ± 58 mg/L), suggesting potential for additional enhancement by increasing SAM availability. Results from this study demonstrate context dependency of engineered pathways and highlight the limited methylation capacity of E. coli. Unlike in previous efforts to improve SAM or

De novo dominant mutation of SOX10 gene in a Chinese family with Waardenburg syndrome type II.

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Chen, Kaitian; Zong, Ling; Liu, Min; Zhan, Yuan; Wu, Xuan; Zou, Wenting; Jiang, Hongyan

2014-06-01

Waardenburg syndrome is a rare genetic disorder, inherited as an autosomal dominant trait. The condition is characterized by sensorineural hearing loss and pigment disturbances of the hair, skin, and iris. The de novo mutation in the SOX10 gene, responsible for Waardenburg syndrome type II, is rarely seen. The present study aimed to identify the genetic causes of Waardenburg syndrome type II in a Chinese family. Clinical and molecular evaluations were conducted in a Chinese family with Waardenburg syndrome type II. A novel SOX10 heterozygous c.259-260delCT mutation was identified. Heterozygosity was not observed in the parents and sister of the proband, indicating that the mutation has arisen de novo. The novel frameshift mutation, located in exon 3 of the SOX10 gene, disrupted normal amino acid coding from Leu87, leading to premature termination at nucleotide 396 (TGA). The high mobility group domain of SOX10 was inferred to be partially impaired. The novel heterozygous c.259-260delCT mutation in the SOX10 gene was considered to be the cause of Waardenburg syndrome in the proband. The clinical and genetic characterization of this family would help elucidate the genetic heterogeneity of SOX10 in Waardenburg syndrome type II. Moreover, the de novo pattern expanded the mutation data of SOX10. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Antecedents of organizational citizenship behavior among Iranian nurses: a multicenter study.

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Taghinezhad, Fakhredin; Safavi, Mahboobe; Raiesifar, Afsaneh; Yahyavi, Sayed Hossein

2015-10-08

Organizational citizenship behavior (OCB) improves efficiency and employees' participation and generally provides a good ambiance. This study was conducted to determine the role of job satisfaction (JS), organizational commitment (OC) and procedural justice (PJ) in explaining OCB among nurses working in fifteen educational-treatment centers in Tehran-Iran, to provide guidelines for health care managers' further understanding of how to encourage citizenship behavior among nurses. In this multi-center descriptive-correlational study 373 nurses were evaluated through a Multi-stage cluster sampling method after obtaining approval from the Ethics Committee of Islamic Azad University, Tehran Medical Branch and Tehran University of Medical Sciences Research Deputy. Nurses who signed the informed consent and holding a bachelor or master degree, having a minimum one year of job experience and not having organizational management position during the questionnaire distribution were included in the study. In order to collect data, Demographic questionnaire, Podsakoff et al. (Leadersh Q 1(2):107-142, 1990) OCB questionnaire, OC questionnaire, Aelterman et al. (Educ Stud 33(3):285-297, 2007) JS questionnaire and PJ questionnaire were used. These questionnaires were translated into Persian and content validity was confirmed by an expert group; their reliability was calculated by the internal consistency Cronbach alpha coefficient and it was satisfied. Data were analyzed by descriptive statistics, Comparative mean tests, correlation coefficient and multiple-regression in the SPSS software version 11. The general mean and all five aspects of OCB that ranked higher than 3 were evaluated in a "quite desired" state. The mean for perceived procedural justice, the general mean for JS and the mean of general grade for OC from the nurses' was in "quite desired" state. Finding from multiple regression indicated that OC and PJ exhibit about 19 % of OCB variance totally which is

De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

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Guella, Ilaria; Huh, Linda; McKenzie, Marna B.; Toyota, Eric B.; Bebin, E. Martina; Thompson, Michelle L.; Cooper, Gregory M.; Evans, Daniel M.; Buerki, Sarah E.; Adam, Shelin; Van Allen, Margot I.; Nelson, Tanya N.; Connolly, Mary B.; Farrer, Matthew J.

2016-01-01

Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report. PMID:27872899

Três casos de hipertensão e Fístula Arteriovenosa Renal: com uma fístula de novo Tres casos de hipertención y Fístula Arteriovenosa Renal: con una fístula de novo Three cases of hypertension and Renal Arteriovenous fistula with a de novo fistula

Directory of Open Access Journals (Sweden)

Natalia Correa Vieira Melo

2009-05-01

Full Text Available Fístula Arteriovenosa Renal (FAVR é uma causa rara e potencialmente reversível de hipertensão e insuficiência renal e/ou cardíaca. O tratamento da FAVR visa preservar o máximo de parênquima renal e, concomitantemente, erradicar os sintomas e efeitos hemodinâmicos decorrentes da FAVR. No presente estudo, serão relatados três casos de FAVR, incluindo um caso de FAVR idiopática de novo, que se apresentaram com hipertensão e insuficiência renal e/ou cardíaca, e descrever a terapêutica adotada e os resultados obtidos.La Fístula Arteriovenosa Renal (FAVR es una causa rara y potencialmente reversible de hipertensión e insuficiencia renal y/o cardíaca. El tratamiento de la FAVR busca preservar el máximo de parénquima renal y, concomitantemente, erradicar los síntomas y efectos hemodinámicos resultantes de la FAVR. En el presente estudio, se relatarán tres casos de FAVR, incluyendo un caso de FAVR idiopática de novo, que se presentaron con hipertensión e insuficiencia renal y/o cardíaca, y describir la terapéutica adoptada y los resultados obtenidos.The Renal Arteriovenous Fistula (RAVF is a rare and potentially reversible cause of hypertension and kidney and/or heart failure. The treatment of RAVF aims at preserving the most of the renal parenchyma and, concomitantly, eradicating the symptoms and hemodynamic effects caused by the RAVF. The present study reports three cases of RAVF, including one case of a de novo idiopathic RAVF, which presented with hypertension and kidney and/or heart failure and describes the therapeutic measures used to treat these patients as well as the outcomes.

Assessment of thromboprophylaxis in medical patients hospitalized in Andalusia. A multicenter study.

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Navarro Puerto, M A; Medrano Ortega, F J; Izquierdo Guerrero, R; Calderón Sandubete, E; Buzón-Barrera, M L; Marín-León, I

2015-04-01

Hospitalized patients are a population at risk for venous thromboembolism (VTE). The PRETEMED-2007 clinical practice guidelines help identify high-risk medical patients who are suited to thromboprophylaxis. These guidelines therefore provide a standard for prophylaxis in such patients. We evaluated the risk of VTE and the adjustment of thromboprophylaxis to the standards of the PRETEMED-2007 guidelines in patients hospitalized in internal medicine departments. An observational, cross-sectional multicenter study was performed in 2010 in 16 hospitals in Andalusia and included 20 consecutive patients per center. The study variables were age, sex, risk factors for VTE and hemorrhage, the risk-adjusted PRETEMED of VTE, adjustment of thromboembolic prophylaxis at admission and at discharge and hospital mortality. The study included 293 patients (57.8% men) with a mean age of 69 (±15) years. The most common triggers for VTE were acute severe infection (27.3%) and neoplasia (16.4%). Some 43.4% of the patients presented a risk of hemorrhage. The risk of VTE at admission and discharge was high in 47.8% and 31% and moderate in 8.2% and 10.6%, respectively. A total of 91.7% and 17.3% of the patients underwent prophylaxis with low-molecular-weight heparin on admission and at discharge, respectively. The prescription was appropriate for 59.9% of the patients at admission (overutilization 38.4%, underutilization 1.7%) and for 74.7% at discharge (overutilization 5.4%, underutilization 19.9%). The adjustment was greater in patients older than 60 years and with greater hemorrhagic risk. For 60% of the patients admitted to the departments of internal medicine in Andalusia, the thromboprophylaxis was appropriate. The inadequacy of thromboprophylaxis (40%) is mostly due to overutilization. These results suggest significant space for improvement. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Nutrition-related risk indexes and long-term mortality in noncritically ill inpatients who receive total parenteral nutrition (prospective multicenter study).

Science.gov (United States)

Tapia, María José; Ocón, Julia; Cabrejas-Gómez, Carmen; Ballesteros-Pomar, María D; Vidal-Casariego, Alfonso; Arraiza-Irigoyen, Carmen; Olivares, Josefina; Conde-García, Ma Carmen; García-Manzanares, Álvaro; Botella-Romero, Francisco; Quílez-Toboso, Rosa P; Cabrerizo, Lucio; Rubio, Miguel A; Chicharro, Luisa; Burgos, Rosa; Pujante, Pedro; Ferrer, Mercedes; Zugasti, Ana; Petrina, Estrella; Manjón, Laura; Diéguez, Marta; Carrera, Ma José; Vila-Bundo, Anna; Urgelés, Juan Ramón; Aragón-Valera, Carmen; Sánchez-Vilar, Olga; Bretón, Irene; García-Peris, Pilar; Muñoz-Garach, Araceli; Márquez, Efren; del Olmo, Dolores; Pereira, José Luis; Tous, María C; Olveira, Gabriel

2015-10-01

Malnutrition in hospitalized patients is associated with an increased risk of death, in both the short and the long term. The purpose of this study was to determine which nutrition-related risk index predicts long-term mortality better (three years) in patients who receive total parenteral nutrition (TPN). This prospective, multicenter study involved noncritically ill patients who were prescribed TPN during hospitalization. Data were collected on Subjective Global Assessment (SGA), Nutritional Risk Index (NRI), Geriatric Nutritional Risk Index (GNRI), body mass index, albumin and prealbumin, as well as long-term mortality. Over the 1- and 3-year follow-up periods, 174 and 244 study subjects (28.8% and 40.3%) respectively, died. Based on the Cox proportional hazards survival model, the nutrition-related risk indexes most strongly associated with mortality were SGA and albumin (Nutrition and Metabolism. All rights reserved.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer.

Science.gov (United States)

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-08-01

Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Cost-effectiveness of healthy eating and/or physical activity promotion in pregnant women at increased risk of gestational diabetes mellitus : Economic evaluation alongside the DALI study, a European multicenter randomized controlled trial

NARCIS (Netherlands)

Broekhuizen, Karen; Simmons, David; Devlieger, Roland; van Assche, André; Jans, Goele; Galjaard, Sander; Corcoy, Rosa; Adelantado, Juan M.; Dunne, Fidelma; Desoye, Gernot; Harreiter, Jürgen; Kautzky-Willer, Alexandra; Damm, Peter; Mathiesen, Elisabeth R.; Jensen, Dorte M.; Andersen, Liselotte L.; Lapolla, Annunziata; Dalfra, Maria G.; Bertolotto, Alessandra; Wender-Ozegowska, Ewa; Zawiejska, Agnieszka; Hill, David; Snoek, Frank J.; Jelsma, Judith G.M.; Bosmans, Judith E.; van Poppel, Mireille N.M.; van Dongen, Johanna M.

2018-01-01

Background: Gestational diabetes mellitus (GDM) is associated with perinatal health risks to both mother and offspring, and represents a large economic burden. The DALI study is a multicenter randomized controlled trial, undertaken to add to the knowledge base on the effectiveness of interventions

Utility of an Abbreviated Dizziness Questionnaire to Differentiate Between Causes of Vertigo and Guide Appropriate Referral: A Multicenter Prospective Blinded Study.

Science.gov (United States)

Roland, Lauren T; Kallogjeri, Dorina; Sinks, Belinda C; Rauch, Steven D; Shepard, Neil T; White, Judith A; Goebel, Joel A

2015-12-01

Test performance of a focused dizziness questionnaire's ability to discriminate between peripheral and nonperipheral causes of vertigo. Prospective multicenter. Four academic centers with experienced balance specialists. New dizzy patients. A 32-question survey was given to participants. Balance specialists were blinded and a diagnosis was established for all participating patients within 6 months. Multinomial logistic regression was used to evaluate questionnaire performance in predicting final diagnosis and differentiating between peripheral and nonperipheral vertigo. Univariate and multivariable stepwise logistic regression were used to identify questions as significant predictors of the ultimate diagnosis. C-index was used to evaluate performance and discriminative power of the multivariable models. In total, 437 patients participated in the study. Eight participants without confirmed diagnoses were excluded and 429 were included in the analysis. Multinomial regression revealed that the model had good overall predictive accuracy of 78.5% for the final diagnosis and 75.5% for differentiating between peripheral and nonperipheral vertigo. Univariate logistic regression identified significant predictors of three main categories of vertigo: peripheral, central, and other. Predictors were entered into forward stepwise multivariable logistic regression. The discriminative power of the final models for peripheral, central, and other causes was considered good as measured by c-indices of 0.75, 0.7, and 0.78, respectively. This multicenter study demonstrates a focused dizziness questionnaire can accurately predict diagnosis for patients with chronic/relapsing dizziness referred to outpatient clinics. Additionally, this survey has significant capability to differentiate peripheral from nonperipheral causes of vertigo and may, in the future, serve as a screening tool for specialty referral. Clinical utility of this questionnaire to guide specialty referral is discussed.

The association between concomitant use of serotonergic antidepressants and lithium-induced polyuria. A multicenter medical chart review study.

Science.gov (United States)

Wilting, I; Egberts, A C G; Movig, K L L; Laarhoven, J H M van; Heerdink, E R; Nolen, W A

2008-07-01

A previous study aimed at revealing the prevalence and determinants of lithium induced polyuria suggested an increased risk of polyuria (urine volume > or =3 L/24 h) in those using serotonergic antidepressants next to lithium. The objective of our study was to re-evaluate this secondary finding in another study population. We performed a multicenter medical chart review study in patients using lithium in whom a 24-hour urine volume had been determined. We included 116 patients, twelve (26%)of the 46 patients with polyuria used serotonergic antidepressants compared to ten (14%) of the 70 patients without polyuria. We found an increased risk of polyuria in lithium users concurrently using serotonergic antidepressants (oddsratio 2.86; 95% confidence interval 1.00-8.21), adjusted for age, gender, use of antiepileptics and thyreomimetics. Our results confirm the previous secondary finding of an increased risk of polyuria in patients using serotonergic antidepressants next to lithium. Physicians should take this into account when evaluating polyuria in patients using lithium and when choosing an antidepressant in patients using lithium.

Los "intelectuales" y el Estado Novo

Directory of Open Access Journals (Sweden)

Luís REIS TORGAL

2010-02-01

Full Text Available RESUMEN: El concepto de “intelectual” es difícil de definir y sin duda se debate constantemente. Sin embargo, es importante reflexionar sobre él a fin de comprender su significado y los problemas que implica. Sea como fuere, a un Estado autoritario “moderno” se le supone una única ideología que tiene que difundirse por medio de una propaganda bien organizada, proceso en el que los intelectuales desempeñan un papel significativo. El “Nuevo Estado” de Salazar encaja en esta categoría y sin duda el conocimiento acerca de sus “intelectuales” es fundamental. En este artículo, el objetivo es proporcionar algunos ejemplos interesantes de “intelectuales” o de simples “funcionarios políticos” con inclinación intelectual a fin de indicar el sentido y complejidad de un estudio con una dimensión distinta sobre este asunto. A este fin han sido seleccionadas tres personalidades responsables de la actividad ideológica y cultural de gran relieve en el Estado de Salazar: António Ferro, João Ameal y Costa Brochado. Palabras clave: Estado Novo; Authotitarianism; Salazar, António de Oliveira; Intellectuals; Ferro, António; Brochado, Idalino da Costa; Ameal, João. ABSTRACT: The concept of the “intellectual” is difficult to define and undoubtedly constantly debated. It is nevertheless important to reflect on it in order to understand its meaning and the problems involved with it. Be that as it may, a “modern” authoritarian State presumes a single ideology which has to be diffused by means of well-organised propaganda, in which process “intellectuals” play a significant role. Salazar’s “New State” fits this category and, undoubtedly, knowledge about its “intellectuals” is fundamental. The objective in this article is to provide some interesting examples of “intellectuals” or simple “political functionar- ies” with an intellectual bent so as to indicate the sense and complexity of a study of a

Factors contributing to disability in rheumatoid arthritis patients: An Egyptian multicenter study.

Science.gov (United States)

Hammad, Marwa; Eissa, Mervat; Dawa, Ghada A

2018-04-30

Minimizing disability and enhancing physical function to its optimal levels is still a challenge in management of rheumatoid arthritis (RA). The aim is to identify factors leading to disability in RA. This is a cross-sectional Egyptian multicenter study carried out on 215 RA patients attending to our inpatient and outpatient rheumatology clinics during 4 months starting from April to July 2017 who agreed to participate in the study; 170 patients were from Cairo University hospitals and 45 from Zagazig University hospitals. We recorded a number of possible risk factors including demographic, clinical, serological and therapeutic factors. The assessment of patients' disability was done using Modified HAQ (MHAQ). A significant positive correlation was found between MHAQ and different markers of activity in addition to age and depression score (P<0.001). Illiteracy accounted for higher MHAQ scores (P=0.001). A higher MHAQ was found in patients with ischemic heart disease (P<0.05). Patients with erosions on X-rays had significantly higher MHAQ scores. Subluxations also accounted for higher MHAQ scores (P=0.000). Aging, illiteracy, disease activity, erosions, subluxations, depression and ischemic heart disease were all related to higher disability. Good control of disease activity which in turn reduces erosions and subluxations is mandatory. Screening for depression and proper use of anti-depressants is of great value. Proper screening and prophylaxis is recommended against ischemic heart disease by controlling modifiable risk factors like obesity, dyslipidaemia, hypertension, smoking and sedentary lifestyle. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

The reliability of echocardiographic left ventricular wall motion index to identify high-risk patients for multicenter studies

DEFF Research Database (Denmark)

Gislason, Gunnar H; Gadsbøll, Niels; Quinones, Miguel A

2006-01-01

that were screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16-segment LV model. RESULTS: The external echocardiographer systematically found lower values of WMI than the core laboratory. The average...... difference in WMI was 0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI ... overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV-WMI as a useful tool for selecting high-risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment...

in silico Whole Genome Sequencer & Analyzer (iWGS): a computational pipeline to guide the design and analysis of de novo genome sequencing studies

Science.gov (United States)

The availability of genomes across the tree of life is highly biased toward vertebrates, pathogens, human disease models, and organisms with relatively small and simple genomes. Recent progress in genomics has enabled the de novo decoding of the genome of virtually any organism, greatly expanding it...

Risk Factors for Malnutrition among Older Adults in the Emergency Department: A Multicenter Study.

Science.gov (United States)

Burks, Collin E; Jones, Christopher W; Braz, Valerie A; Swor, Robert A; Richmond, Natalie L; Hwang, Kay S; Hollowell, Allison G; Weaver, Mark A; Platts-Mills, Timothy F

2017-08-01

Among older adults, malnutrition is common, often missed by healthcare providers, and influences recovery from illness or injury. To identify modifiable risk factors associated with malnutrition in older patients. Prospective cross-sectional multicenter study. 3 EDs in the South, Northeast, and Midwest. Non-critically ill, English-speaking adults aged ≥65 years. Random time block sampling was used to enroll patients. The ED interview assessed malnutrition using the Mini Nutritional Assessment Short-Form. Food insecurity and poor oral health were assessed using validated measures. Other risk factors examined included depressive symptoms, limited mobility, lack of transportation, loneliness, and medication side effects, qualified by whether the patient reported the risk factor affected their diet. The population attributable risk proportion (PARP) for malnutrition was estimated for each risk factor. In our sample (n = 252), the prevalence of malnutrition was 12%. Patient characteristics associated with malnutrition included not having a college degree, being admitted to the hospital, and residence in an assisted living facility. Of the risk factors examined, the PARPs for malnutrition were highest for poor oral health (54%; 95% CI 16%, 78%), food insecurity (14%; 95% CI 3%, 31%), and lack of transportation affecting diet (12%; 95% CI 3%, 28%). Results of this observational study identify multiple modifiable factors associated with the problem of malnutrition in older adults. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Normative data for Aδ contact heat evoked potentials in adult population: a multicenter study.

Science.gov (United States)

Granovsky, Yelena; Anand, Praveen; Nakae, Aya; Nascimento, Osvaldo; Smith, Benn; Sprecher, Elliot; Valls-Solé, Josep

2016-05-01

There has been a significant increase over recent years in the use of contact heat evoked potentials (CHEPs) for the evaluation of small nerve fiber function. Measuring CHEP amplitude and latency has clinical utility for the diagnosis and assessment of conditions with neuropathic pain. This international multicenter study aimed to provide reference values for CHEPs to stimuli at 5 commonly examined body sites. Contact heat evoked potentials were recorded from 226 subjects (114 females), distributed per age decade between 20 and 79 years. Temperature stimuli were delivered by a thermode (32°C-51°C at a rate of 70°C/s). In phase I of the study, we investigated side-to-side differences and reported the maximum normal side-to-side difference in Aδ CHEP peak latency and amplitude for leg, forearm, and face. In phase II, we obtained normative data for 3 CHEP parameters (N2P2 amplitude, N2 latency, and P2 latency), stratified for gender and age decades from face, upper and lower limbs, and overlying cervical and lumbar spine. In general, larger CHEP amplitudes were associated with higher evoked pain scores. Females had CHEPs of larger amplitude and shorter latency than males. This substantive data set of normative values will facilitate the clinical use of CHEPs as a rapid, noninvasive, and objective technique for the assessment of patients presenting with neuropathic pain.

Association of Fetal Abdominal–Head Circumference Size Difference With Shoulder Dystocia: A Multicenter Study

Science.gov (United States)

Endres, Loraine; DeFranco, Emily; Conyac, Theresa; Adams, Marci; Zhou, Ying; Magner, Kristin; O'Rourke, Luke; Bernhard, Kiley A.; Siddiqui, Danish; McCormick, Anna; Abramowicz, Jacques; Merkel, Ronald; Jawish, Rana; Habli, Mounira; Floman, Alissa; Magann, Everett F.; Chauhan, Suneet P.

2015-01-01

Objective This study aims to determine if shoulder dystocia is associated with a difference in the fetal abdominal (AC) to head circumference (HC) of 50 mm or more noted on antenatal ultrasound. Study Design A multicenter matched case–control study was performed comparing women who had shoulder dystocia to controls who did not. Women with vaginal births of live born nonanomalous singletons ≥ 36 weeks of gestation with an antenatal ultrasound within 4 weeks of delivery were included. Controls were matched for gestational age, route of delivery, and diabetes status. Results We identified 181 matched pairs. Only 5% of the fetuses had an AC to HC of ≥ 50 mm. The proportion of AC to HC difference of ≥ 50 mm was significantly higher in shoulder dystocia cases (8%) than controls (1%, p = 0.002). With multivariate regression, the three significant factors associated with shoulder dystocia were AC to HC ≥ 50 mm (odds ratio [OR], 7.3; confidence interval [CI], 1.6–33.3; p = 0.010), femur length (OR, 1.1; CI, 1.0–1.2; p = 0.002), and induced labor (OR, 1.8; CI, 1.1–3.1; p = 0.027). Conclusion A prenatal ultrasound finding of a difference in AC to HC of ≥ 50 mm while uncommon is associated with shoulder dystocia. PMID:26495163

Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience

NARCIS (Netherlands)

Prummel, Mark F.; Bakker, Annemieke; Wiersinga, Wilmar M.; Baldeschi, Lelio; Mourits, Maarten P.; Kendall-Taylor, Pat; Perros, Petros; Neoh, Chris; Dickinson, A. Jane; Lazarus, John H.; Lane, Carol M.; Heufelder, Armin E.; Kahaly, George J.; Pitz, Suzanne; Orgiazzi, Jacques; Hullo, Alain; Pinchera, Aldo; Marcocci, Claudio; Sartini, Maria S.; Rocchi, Roberto; Nardi, Marco; Krassas, Gerry E.; Halkias, A.

2003-01-01

To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on

EX-MET study: exercise in prevention on of metabolic syndrome - a randomized multicenter trial: rational and design.

Science.gov (United States)

Tjønna, Arnt Erik; Ramos, Joyce S; Pressler, Axel; Halle, Martin; Jungbluth, Klaus; Ermacora, Erika; Salvesen, Øyvind; Rodrigues, Jhennyfer; Bueno, Carlos Roberto; Munk, Peter Scott; Coombes, Jeff; Wisløff, Ulrik

2018-04-02

Metabolic syndrome substantially increases risk of cardiovascular events. It is therefore imperative to develop or optimize ways to prevent or attenuate this condition. Exercise training has been long recognized as a corner-stone therapy for reducing individual cardiovascular risk factors constituting the metabolic syndrome. However, the optimal exercise dose and its feasibility in a real world setting has yet to be established. The primary objective of this randomized trial is to investigate the effects of different volumes of aerobic interval training (AIT) compared to the current exercise guideline of moderate-intensity continuous training (MICT) on the composite number of cardiovascular disease risk factors constituting the metabolic syndrome after a 16 week, 1-year, and 3-year follow-up. This is a randomized international multi-center trial including men and women aged ≥30 years diagnosed with the metabolic syndrome according to the International Diabetes Federation criteria. Recruitment began in August 2012 and concluded in December 2016. This trial consists of supervised and unsupervised phases to evaluate the efficacy and feasibility of different exercise doses on the metabolic syndrome in a real world setting. This study aims to include and randomize 465 participants to 3 years of one of the following training groups: i) 3 times/week of 4 × 4 min AIT at 85-95% peak heart rate (HRpeak); ii) 3 times/week of 1 × 4 min AIT at 85-95% HRpeak; or iii) 5-7 times/week of ≥30 min MICT at 60-70% HRpeak. Clinical examinations, physical tests and questionnaires are administered to all participants during all testing time points (baseline, 16 weeks and after 1-, and 3-years). This multi-center international trial indeed aims to ease the burden in healthcare/economic cost arising from treating end-stage CVD related conditions such as stroke and myocardial infarction, that could eventually emerge from the metabolic syndrome condition. Clinical

Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?

Directory of Open Access Journals (Sweden)

Banović Marko

2010-01-01

Full Text Available Introduction. Acute heart failure (AHF is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. Objective. To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF and to identify differences in blood levels of biomarkers and echocardiography findings. Methods. This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%, and patients with acute worsening of CHF (54.7%. Results. Acute congestion (60% was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1% was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 μmol/l; p<0.05, urea (12.63 vs 7.82 mmol/l; p<0.05, BNP (1440.11 vs 712.24 pg/ml; p<001 and NTproBNP (9097.00 vs 2827.70 pg/ml; p<0.01 on admission, and lower values of M-mode left ventricular ejection fraction (LVEF during hospitalization (49.44% vs 42.94%; p<0.05. The follow-up after one year revealed still significantly higher BNP (365.49 vs 164.02 pg/ ml; p<0.05 and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs 54.41% and 39.52% vs 47.88%; p<0.05. Conclusion. Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

Sentinel node biopsy for early-stage melanoma - Accuracy and morbidity in MSLT-I, an international multicenter trial

NARCIS (Netherlands)

Morton, DL; Cochran, AJ; Thompson, JF; Elashoff, R; Essner, R; Glass, EC; Mozzillo, N; Nieweg, OE; Roses, DF; Hoekstra, HJ; Karakousis, CP; Reintgen, DS; Coventry, BJ; Wang, HJ

Objective:The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. Summary

Effectiveness and Persistence with Liraglutide Among Patients with Type 2 Diabetes in Routine Clinical Practice--EVIDENCE: A Prospective, 2-Year Follow-Up, Observational, Post-Marketing Study.

Science.gov (United States)

Gautier, Jean-Francois; Martinez, Luc; Penfornis, Alfred; Eschwège, Eveline; Charpentier, Guillaume; Huret, Benoît; Madani, Suliya; Gourdy, Pierre

2015-09-01

The aim of this study was to investigate whether the efficacy of liraglutide observed in randomized controlled trials translates into therapeutic benefits in the French population during routine clinical practice. This observational, prospective, multicenter study included 3152 adults with type 2 diabetes who had recently started or were about to start liraglutide treatment. During 2 years of follow-up, an evaluation of the reasons for prescribing liraglutide, maintenance dose of liraglutide, changes in combined antidiabetic treatments, level of glycemic control, change in body weight and body mass index (BMI), patient satisfaction with diabetes treatment and safety of liraglutide were investigated. The primary study endpoint was the proportion of patients still receiving liraglutide and presenting with HbA1c effectiveness of liraglutide in real-world clinical practice is similar to that observed in randomized controlled trials. Novo Nordisk A/S. ClinicalTrials.gov identifier, NCT01226966.

Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis.

Science.gov (United States)

Kumagai, Jinpei; Hofland, Johannes; Erkens-Schulze, Sigrun; Dits, Natasja F J; Steenbergen, Jacobie; Jenster, Guido; Homma, Yukio; de Jong, Frank H; van Weerden, Wytske M

2013-11-01

Despite an initial response to hormonal therapy, patients with advanced prostate cancer (PC) almost always progress to castration-resistant disease (CRPC). Although serum testosterone (T) is reduced by androgen deprivation therapy, intratumoral T levels in CRPC are comparable to those in prostate tissue of eugonadal men. These levels could originate from intratumoral conversion of adrenal androgens and/or from de novo steroid synthesis. However, the relative contribution of de novo steroidogenesis to AR-driven cell growth is unknown. The relative contribution of androgen biosynthetic pathways to activate androgen receptor (AR)-regulated cell growth and expression of PSA, FKBP5, and TMPRSS2 was studied at physiologically relevant levels of adrenal androgen precursors and intermediates of de novo androgen biosynthesis in human prostate cancer cell lines, PC346C, VCaP, and LNCaP. In PC346C and VCaP, responses to pregnenolone and progesterone were absent or minimal, while large effects of adrenal androgen precursors were found. VCaP CRPC clones overexpressing CYP17A1 did not acquire an increased ability to use pregnenolone or progesterone to activate AR. In contrast, all precursors stimulated growth and gene expression in LNCaP cells, presumably resulting from the mutated AR in these cells. Our data indicate that at physiological levels of T precursors PC cells can generally convert adrenal androgens, while de novo steroidogenesis is not generally possible in PC cells and is not able to support AR transactivation and PC growth. © 2013 Wiley Periodicals, Inc.

Multicenter study differentiated thyroid carcinoma (MSDS). Diminished acceptance of adjuvant external beam radiotherapy

International Nuclear Information System (INIS)

Biermann, M.; Pixberg, M.K.; Schober, O.; Schuck, A.; Willich, N.; Heinecke, A.; Koepke, W.; Schmid, K.W.; Dralle, H.

2003-01-01

Aim: The Multicenter Study Differentiated Thyroid Carcinoma (MSDS) is an ongoing study in Germany, Austria, and Switzerland on the clinical benefit of adjuvant external beam radiotherapy (RTx) for locally invasive differentiated thyroid carcinoma (DTC) in TNM stages pT4 pNO/1/xMO/x (5th ed. 1997). Methods: MSDS was designed as a prospective randomized trial. Patients receive thyroidectomy, radioiodine therapy (RIT) to ablate the thyroid remnant, and TSH-suppressive L-thyroxine therapy with or without RTx after documented elimination of cervical iodine-131 uptake (http://msds-studie.uni-muenster.de). Results: 311 patients were enrolled between January 2000 and March 2003. 279 patients met the trial's inclusion criteria. 45 consented to randomization, of whom 17 were randomized into treatment arm A (RTx) and 18 into arm B (no RTx). Advised by the trial's independent Data Monitoring and Safety Committee, the MSDS steering committee decided to terminate randomization in April 2003 and continue MSDS as a prospective cohort study. 23 of the 234 patients in the observation arm of the trial were prescribed RTx by their physicians. Thus, 14% of the trial cohort were randomized or assigned to receive RTx (intention-to-treat analysis). In contrast, at least 44% of all patients with pT4 papillary DTC in Germany in the nationwide PCES study underwent RTx in 1996 (p 2 -test). Conclusions: Acceptance of external beam RTx as a treatment modality for DTC has receded to a degree that accrual of a sufficient number of patients for a randomized trial has been impossible. Observation of the trial cohort is continued in order to assess clinical event rates with and without RTx and chronic RTx toxicity. (orig.) [de

Shigella isolates from the global enteric multicenter study inform vaccine development.

Science.gov (United States)

Livio, Sofie; Strockbine, Nancy A; Panchalingam, Sandra; Tennant, Sharon M; Barry, Eileen M; Marohn, Mark E; Antonio, Martin; Hossain, Anowar; Mandomando, Inacio; Ochieng, John B; Oundo, Joseph O; Qureshi, Shahida; Ramamurthy, Thandavarayan; Tamboura, Boubou; Adegbola, Richard A; Hossain, Mohammed Jahangir; Saha, Debasish; Sen, Sunil; Faruque, Abu Syed Golam; Alonso, Pedro L; Breiman, Robert F; Zaidi, Anita K M; Sur, Dipika; Sow, Samba O; Berkeley, Lynette Y; O'Reilly, Ciara E; Mintz, Eric D; Biswas, Kousick; Cohen, Dani; Farag, Tamer H; Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C; Kotloff, Karen L; Nataro, James P; Levine, Myron M

2014-10-01

Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children aged Shigella was 1 of the 4 most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto xylose lysine desoxycholate and MacConkey agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore, MD) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to the Centers for Disease Control and Prevention for quality control. Shigella dysenteriae and S. boydii accounted for 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b, and S. flexneri 1b. A broad-spectrum Shigella vaccine must protect against S. sonnei and 15 S. flexneri serotypes/subserotypes. A quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but 1 (rare) remaining subserotype through shared S. flexneri group antigens. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study

Science.gov (United States)

Liang, Ying; Cao, Changan; Zhu, Cheng; Wang, Chuanyue; Zhang, Congpei; Dong, Fang; Yang, Fude; Deng, Hong; Yu, Jingjie; Tang, Jisheng; Su, Lei; Xin, Limin; Hong, Ling; Gao, Minglong; Tang, Muni; Xie, Shiping; Lu, Shuiping; Liu, Tiebang; Xu, Xiaojin; Wang, Xijin; Li, Xuanzi; Wang, Xueyi; Li, Yi; Zhang, Yong; Chen, Zhiyu

2016-01-01

Abstract Introduction This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients. Methods A multicenter, single‐arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Results A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events. Discussion Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia. PMID:27020720

Radiotherapy, especially at young age, increases the risk for de novo brain tumors in patients treated for pituitary tumors

NARCIS (Netherlands)

Burman, Pia; Van Beek, André P.; Biller, Beverly M.K.; Camacho-Hubner, Cecilia; Mattsson, Anders F.

Background: Excess mortality due to de novo malignant brain tumors was recently found in a national study of patients with hypopituitarism following treatment of pituitary tumors. Here, we examined a larger multi-national cohort to corroborate and extend this observation. Objective: To investigate

Scattering of charged particles by a multicenter potential

International Nuclear Information System (INIS)

Gerasimov, O.I.; Stienko, A.G.

1994-01-01

Exact expressions are obtained for the amplitude and elastic cross section in the case of scattering of charged particles by a multicenter pseudopotential that includes the Coulomb potential and an arbitrary number of short-range potentials (modeled by zero-range potentials). Asymptotic limits are calculated and explicit expressions are found for the amplitudes of scattering by few-nucleon complexes modeled by superpositions of the Coulomb potential and purely point potentials

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

Science.gov (United States)

Nakai, Yousuke; Yamamoto, Ryuichi; Matsuyama, Masato; Sakai, Yuji; Takayama, Yukiko; Ushio, Jun; Ito, Yukiko; Kitamura, Katsuya; Ryozawa, Shomei; Imamura, Tsunao; Tsuchida, Kouhei; Hayama, Jo; Itoi, Takao; Kawaguchi, Yoshiaki; Yoshida, Yu; Sugimori, Kazuya; Shimura, Kenji; Mizuide, Masafumi; Iwai, Tomohisa; Nishikawa, Ko; Yagioka, Hiroshi; Nagahama, Masatsugu; Toda, Nobuo; Saito, Tomotaka; Yasuda, Ichiro; Hirano, Kenji; Togawa, Osamu; Nakamura, Kenji; Maetani, Iruru; Sasahira, Naoki; Isayama, Hiroyuki

2018-05-01

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Axial Globe Position Measurement: A Prospective Multi-center Study by the International Thyroid Eye Disease Society

Science.gov (United States)

Bingham, Chad M.; Sivak-Callcott, Jennifer A.; Gurka, Matthew J.; Nguyen, John; Hogg, Jeffery P.; Feldon, Steve E.; Fay, Aaron; Seah, Lay-Leng; Strianese, Diego; Durairaj, Vikram D.; Uddin, Jimmy; Devoto, Martin H.; Harris, Matheson; Saunders, Justin; Osaki, Tammy H.; Looi, Audrey; Teo, Livia; Davies, Brett W.; Elefante, Andrea; Shen, Sunny; Realini, Tony; Fischer, William; Kazim, Michael

2015-01-01

Purpose Identify a reproducible measure of axial globe position (AGP) for multicenter studies of patients with thyroid eye disease (TED). Methods This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, computed tomography (CT) was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer, not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times, not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, ICC’s, Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using intraclass correlation coefficients (ICC). Results Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37mm (15.96 – 28.90mm) right, 21.22mm (15.87 – 28.70mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18mm and 25mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948 – 0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47mm (10.92 – 30

Emotional exhaustion is associated with work related stressors: a cross-sectional multicenter study in Malaysian public hospitals.

Science.gov (United States)

Khoo, Erwin J; Aldubai, Sami; Ganasegeran, Kurubaran; Lee, Bernice Xe; Zakaria, Nurul A; Tan, Kah K

2017-06-01

Emotional exhaustion is an important component of burnout. Burnout is common among doctors. It affects the physical and mental health of doctors, their performance and the quality of care they provide. This study aimed to investigate the level and factors associated with emotional exhaustion among doctors in pediatric practice in Malaysia. A self-administered questionnaire was used in this multicenter cross-sectional study. It included questions on the socio-demographics, work characteristics, Emotional Exhaustion, Perceived Stress Scale and sources of job stress. Descriptive, univariate and multivariate analysis were conducted using the SPSS software. A total of 197 doctors working in the Pediatric department in eight hospitals returned complete questionnaire. High and moderate emotional exhaustion was reported by 25.4% and 24.4% doctors, respectively. In bivariate analysis, 29 out of the 38 items of sources of stress showed significant association with emotional exhaustion (p appreciation from supervisors, lack of incentives and promotions, time pressures and deadlines to meet, and setting unrealistic goals of having them imposed on oneself (p workplace but not with socio-demographic factors.

Health status, resource consumption, and costs of dysthymia. A multi-center two-year longitudinal study.

Science.gov (United States)

Barbui, Corrado; Motterlini, Nicola; Garattini, Livio

2006-02-01

In this study we estimated the health status, resource consumption and costs of a large cohort of patients with early and late-onset dysthymia. The DYSCO (DYSthymia COsts) project is a multi-center observational study which prospectively followed for two years a randomly chosen sample of patients with dysthymia in the Italian primary health care system. A total of 501 patients were followed for two years; 81% had early-onset dysthymic disorder. During the study, improvement was seen in most domains of the 36-Item Short Form Health Survey (SF-36) questionnaire. Comparison of the SF-36 scores for the two groups showed that only the physical health index significantly differed during the two years. The use of outpatient consultations, laboratory tests and diagnostic procedures was similar in the two groups, but patients with early-onset dysthymia were admitted significantly more than late-onset cases. Hospital admissions were almost entirely responsible for the higher total cost per patient per year of early-onset dysthymia. A first limitation of this study is that general practitioners were selected on the basis of their willingness to participate, not at random; secondly, no information was collected on concomitant psychiatric comorbidities. The present study provides the first prospective, long-term data on service use and costs in patients with dysthymia. Differently from patients with early-onset dysthymia, patients with late-onset dysthymia were admitted less and cost less.

Contrôle genético dos "frutos chochos" no Café "Mundo Novo" Manofactorial inheritance of "empty-locule" in the Mundo Novo coffee

Directory of Open Access Journals (Sweden)

A. J. T. Mendes

1955-01-01

-cut separation of Mundo Novo coffee populations into two classes : a plants in which the discoid endosperm is not formed (normal plants ; and b plants in which the disc occurs (hight percentage of empty locules. A survey was made of three Mundo Novo plantings representing different generations of an once-existing small group of plants. Under the assumption that the original plants (maximum of eight plants were Dd (F1, the first plantings made with their seeds represented F2 populations and should have DD and Dd individuals in a ratio of 1:2. A second planting has been made with seed collected from 400 plants that represented another group of the supposed F2 generation; assuming that this F2 had 1DD:2Dd, and that 10% of cross pollination occurred, this F3 population should consist of DD and Dd individuals in the ratio of 59:41. A third group of plants that was examined had been planted with seed collected from 15 plants selected from the first planting of the F2 generation. Sampling of these 15 parent plants indicated that according to the presence of discoid endosperm they were 4DD:11Dd; assuming that 10% of cross pollination occurred and taking into account that an equal number (20 of seedlings was selected from each progeny, it was expected that the ratio in this F3 lot would be 51:49. Samples of 100,100, and 262 plants that were examined in the one lot that represented an F2 generation and in the two others that represented F3 generations, respectively, confirmed the above-mentioned expectations. Individual study of the plants belonging to the 15 progenies showed that the 197 plants derived from the 11 Dd plants were in the ratio of 1DD:2Dd; among the 65 plants derived from the 4 DD individuals, only four were Dd, which corresponds closely to a possible 10% of cross pollination. Emasculated flowers of Dd plants that were pollinated with DD pollen produced only normal seeds, thus confirming the genetic origin of empty locules. The frequency of empty locules only seldom reaches

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

DEFF Research Database (Denmark)

Muona, M.; Berkovic, S. F.; Dibbens, L. M.

2015-01-01

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonicclonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo...

A multicenter reproducibility study of single-voxel 1H-MRS of the medial temporal lobe

International Nuclear Information System (INIS)

Traeber, Frank; Block, Wolfgang; Guer, Okan; Schild, Hans H.; Freymann, Nikolaus; Heun, Reinhard; Jessen, Frank; Kucinski, Thomas; Hammen, Thilo; Ende, Gabriele; Pilatus, Ulrich; Hampel, Harald

2006-01-01

Proton magnetic resonance spectroscopy ( 1 H-MRS) has provided evidence for a reduction of N-acetyl-aspartate (NAA) in the medial temporal lobe (MTL) in cerebral disorders such as Alzheimer's Disease. Within the 1 H-MRS study of the German Research Network on Dementia, we determined the multicenter reproducibility of single-voxel 1 H-MRS of the MTL. At five sites with 1.5T MR systems, single-voxel 1 H spectra from the MTL of an identical healthy subject were measured. The same subject was also examined at one of the sites five times to assess intracenter stability. The protocol included water-suppressed spectra with TE 272 ms and TE 30 ms and unsuppressed spectra for absolute quantification of metabolite concentrations. The intracenter reproducibility of absolute NAA concentration, expressed as coefficient of variation (CV), was 1.8%. CV for the concentrations of creatine (Cr), choline (Cho), and myoinositol (MI) and for the ratios NAA/Cr, NAA/Cho, and MI/NAA varied by 11-16%. Intercenter CV was 3.9% for NAA and were below 10% for all other metabolites and metabolic ratios. Our study demonstrates that quantitative assessment of NAA with single-voxel MRS can be performed with high intercenter reproducibility. This is the basis for applying 1 H-MRS in large-scale early recognition and treatment studies in MTL affecting disorders. (orig.)

A SA8000 e a responsabilidade social das empresas: a emergência de um novo paradigma?

OpenAIRE

Lopes, Ana Catarina Marques Figueiredo Caetano

2004-01-01

Mestrado em Desenvolvimento e Cooperação Internacional A Responsabilidade Social das Empresas, não é um tema novo. Durante muito tempo foi discutido e interpretado no âmbito do debate sobre as responsabilidades que uma empresa deve assumir para além daquelas que tem perante os seus accionistas, e das impostas por lei. Hoje, observamos a emergência de um novo paradigma assente no reconhecimento que o sector privado não só pode, mas deve, fazer mais para combater a pobreza, preservar o meio ...

Conversion to belatacept in maintenance kidney-transplant patients: A retrospective multicenter European study.

Science.gov (United States)

Darres, Amandine; Ulloa, Camillo; Brakemeier, Susanne; Garrouste, Cyril; Bestard, Oriol; Del Bello, Arnaud; Sberro Soussan, Rebecca; Dürr, Michael; Budde, Klemens; Legendre, Christophe; Kamar, Nassim

2018-03-22

The use of belatacept is not yet approved for maintenance kidney-transplant patients. This retrospective multicenter European study aimed to assess the efficacy and safety of conversion to belatacept in a large cohort of patients in a real-life setting, and to identify the predictive factors for improved kidney function after the switch. Two-hundred and nineteen maintenance kidney-transplant patients from 5 European kidney-transplant centers were converted to belatacept at 21.2 (0.1-337.1) months posttransplantation, mainly because of impaired kidney function. Thirty-two patients were converted to belatacept within the first 3 months posttransplantation. The mean duration of follow-up was 21.9±20.2 months. The actuarial rate of patients still on belatacept-based therapy was 77.6%. Mean estimated glomerular-filtration rate (eGFR) increased from 32±16.4 at baseline to 38±20 mL/min/1.73 m (ppredictive factor for a significant increase in eGFR (of 5 and 10 mL/min/1.73 m at 3 and 12 months after the switch, respectively). Eighteen patients (8.2%) presented with an acute-rejection episode after conversion; 3 developed a donor-specific antibody (DSA). Overall efficacy and safety were good, including for the 35 patients that had a DSA at conversion. The conversion to belatacept was effective, especially when performed early after transplantation.

A multicenter prospective study to assess the effect of early cleavage on embryo quality, implantation, and live-birth rate.

Science.gov (United States)

de los Santos, Maria José; Arroyo, Gemma; Busquet, Ana; Calderón, Gloria; Cuadros, Jorge; Hurtado de Mendoza, Maria Victoria; Moragas, Marta; Herrer, Raquel; Ortiz, Agueda; Pons, Carme; Ten, Jorge; Vilches, Miguel Angel; Figueroa, Maria José

2014-04-01

To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates. Prospective cross-sectional study. Multicenter study. Seven hundred embryo transfers and 1,028 early-stage human embryos. None. Implantation according to the presence of EC and embryo quality. The presence of EC is associated with embryo quality, especially in cycles with autologous oocytes. However, the use of EC as an additional criterion for selecting an embryo for transfer does not appear to significantly improve likelihood of implantation. Furthermore, embryos that presented EC had live-birth rates per implanted embryo similar to those that did not show any sign of cleavage. At least for conventional embryo culture and morphologic evaluations, the additional evaluation of EC in embryos may not be valuable to improve embryo implantation. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Antimicrobial peptide capsids of de novo design.

Science.gov (United States)

De Santis, Emiliana; Alkassem, Hasan; Lamarre, Baptiste; Faruqui, Nilofar; Bella, Angelo; Noble, James E; Micale, Nicola; Ray, Santanu; Burns, Jonathan R; Yon, Alexander R; Hoogenboom, Bart W; Ryadnov, Maxim G

2017-12-22

The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that-by emulating the virus architecture-assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function-they destroy bacteria on contact.

The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study.

Science.gov (United States)

Mekinian, Arsène; Lazzaroni, Maria Grazia; Kuzenko, Anna; Alijotas-Reig, Jaume; Ruffatti, Amelia; Levy, Pierre; Canti, Valentina; Bremme, Katarina; Bezanahary, Holy; Bertero, Tiziana; Dhote, Robin; Maurier, Francois; Andreoli, Laura; Benbara, Amélie; Tigazin, Ahmed; Carbillon, Lionel; Nicaise-Roland, Pascale; Tincani, Angela; Fain, Olivier

2015-06-01

In European multicenter study, we aimed to describe the real-life hydroxychloroquine use in APS patients during pregnancy and determine its benefit in refractory obstetrical APS. We analyzed the outcome of pregnancies treated by hydroxychloroquine in patients with APS or asymptomatic antiphospholipid (aPL) antibodies carriers. Thirty patients with APS with 35 pregnancies treated by hydroxychloroquine were analyzed. Comparing the outcome of pregnancies treated by the addition of hydroxychloroquine to previous pregnancies under the conventional treatment, pregnancy losses decreased from 81% to 19% (phydroxychloroquine amount (400mg per day) were the factors associated with pregnancy outcome. Considering 14 patients with previous refractory obstetrical APS (n=5 with obstetrical and thrombotic primary APS and n=9 with purely obstetrical APS), all with previous pregnancy losses under treatment (aspirin with LMWH in 11 cases and LMWH in 3 cases), the addition of hydroxychloroquine resulted in live born babies in 11/14 (78%) cases (phydroxychloroquine addition in patients with refractory obstetrical APS and raises the need of prospective studies to confirm our preliminary study. Copyright © 2015 Elsevier B.V. All rights reserved.

COMPULS: design of a multicenter phenotypic, cognitive, genetic, and magnetic resonance imaging study in children with compulsive syndromes

Directory of Open Access Journals (Sweden)

Jilly Naaijen

2016-10-01

Full Text Available Abstract Background Compulsivity, the closely linked trait impulsivity and addictive behaviour are associated with several neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD, autism spectrum disorder (ASD, and obsessive compulsive disorder (OCD. All three disorders show impaired fronto-striatal functioning, which may be related to altered glutamatergic signalling. Genetic factors are also thought to play an important role in the aetiology of compulsivity-related disorders. Methods The COMPULS study is a multi-center study designed to investigate the relationship between the traits compulsivity, impulsivity, and, to a lesser extent, addictive behaviour within and across the neurodevelopmental disorders ADHD, ASD, and OCD. This will be done at the phenotypic, cognitive, neural, and genetic level. In total, 240 participants will take part in COMPULS across four different sites in Europe. Data collection will include diagnostic interviews, behavioural questionnaires, cognitive measures, structural, functional and spectral neuroimaging, and genome-wide genetic information. Discussion The COMPULS study will offer the unique opportunity to investigate several key aspects of compulsivity across a large cohort of ADHD, ASD and OCD patients.

[Multicenter Ozurdex® assessment for diabetic macular edema: MOZART study].

Science.gov (United States)

Guigou, S; Hajjar, C; Parrat, E; Merite, P Y; Pommier, S; Matonti, F; Prost-Magnin, O; Meyer, F

2014-06-01

To evaluate the efficiency and safety of intravitreal implant of 0.7mg dexamathasone in visual impairment due to diabetic macular edema (DME). This was a retrospective, multicenter, study. Seventy-four patients, with a mean age of 65 years, followed for at least 6 months (mean follow-up: 9.8 months) were included in 5 French eye clinics (P 1.5 collective). The mean systolic blood pressure was 138mmHg and the mean HbA1c was 7.2%. We monitored 2 systemic parameters: blood pressure and glycemic balance. Best-corrected visual acuity (BCVA), central retinal thickness (CRT, Spectralis OCT), intraocular pressure (IOP) and cataract progression are studied at baseline and then at 1, 2, 4 and 6 months. The average CRT decrease was: 239μm at month 2 (M2) and 135μm at month 6 (M6). The mean improvement from baseline of BCVA is 8.5 letters at M2 and 7.6 letters at M6. A gain greater than 15 letters is found in 27% of patients at M6. For naive patients the BCVA is 71 letters versus 60 letters (P<0.05). Patients with a baseline CRT <500mmHg have a BCVA of 66 letters versus 57 letters (P<0.05). The mean rate injections was 1.2 at 6 months with an average of 5.4 months for reinjection. Ocular hypertension greater than 25mmHg, managed by topical treatment, is observed in 13.4% of patients. No glaucoma surgery was necessary. Dexamethasone has an anatomical and functional effectiveness in the treatment of DME. Outcomes for naive patients and lower CRT suggest that the duration of diabetes mellitus and previous treatments are negative factors of recovery. Side effects are rare and manageable. Ozurdex(®) seems to be a treatment for visual impairment due to DME with a favorable safety profile. Patient follow-up must be adapted to half-life of the product with a control before M1 (intraocular pressure) and before M5 (DME recurrence, BCVA). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Neonatal outcome following new assisted reproductive technology regulations in Turkey - a nationwide multicenter point prevalence study.

Science.gov (United States)

Kultursay, Nilgun; Yalaz, Mehmet; Koroglu, Ozge Altun

2015-01-01

In March 2010, a new legislation about assisted reproductive technology (ART) activities, favoring single embryo transfer, was introduced in Turkey. Consequences of new regulations on neonatal outcome have not been evaluated in multicenter studies yet. In this study, our aim was to evaluate neonatal outcome of infants from medically assisted reproduction (MAR) pregnancies in the post-legislation era. A point prevalence study was conducted at 51 centers in Turkey on 1 April 2013. Data about fertility treatments and neonatal characteristics were evaluated for "live births" (Group 1) and "patients being cared in the NICU" (Group 2). Seventeen (4%) of 420 infants in group 1, and 89 (8.1%) of 1094 infants in group 2 were born after MAR pregnancies. The ratio of multiple births in MAR pregnancies was still very high as 47.1% for group 1, 69.1% for group 2 infants. MAR babies constituted 9.9% of infants in Level 3 NICUs and 7.6% infants in Level 2 NICUs. MAR was associated with increased risk of multiple births and prematurity. After the new legislation, multiple birth rates are still high in MAR pregnancies, resulting in unfavorable neonatal outcomes. Efforts to decrease multiple birth rates should be encouraged.

Linear mixed-effects models for central statistical monitoring of multicenter clinical trials

OpenAIRE

Desmet, L.; Venet, D.; Doffagne, E.; Timmermans, C.; BURZYKOWSKI, Tomasz; LEGRAND, Catherine; BUYSE, Marc

2014-01-01

Multicenter studies are widely used to meet accrual targets in clinical trials. Clinical data monitoring is required to ensure the quality and validity of the data gathered across centers. One approach to this end is central statistical monitoring, which aims at detecting atypical patterns in the data by means of statistical methods. In this context, we consider the simple case of a continuous variable, and we propose a detection procedure based on a linear mixed-effects model to detect locat...

Adversity and Syndemic Production Among Men Participating in the Multicenter AIDS Cohort Study: A Life-Course Approach

Science.gov (United States)

Lim, Sin How; Plankey, Michael W.; Chmiel, Joan S.; Guadamuz, Thomas T.; Kao, Uyen; Shoptaw, Steven; Carrico, Adam; Ostrow, David; Stall, Ron

2013-01-01

Objectives. We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study. Methods. Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland–Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production. Results. Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ2 = 247.94; P < .001; df = 22). Conclusions. We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM. PMID:23153154

A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia.

Science.gov (United States)

Li, Xin; Li, Juan; Hu, Yanjie; Xie, Wei; Du, Wen; Liu, Wei; Li, Xiaoqing; Chen, Xiangjun; Li, Hongrui; Wang, Junfeng; Zhang, Lannan; Huang, Shiang

2012-06-01

Cytogenetics and molecular cytogenetics of 1466 Chinese patients with de novo acute lymphoblastic leukemia (ALL) were studied. Cytogenetic results were available in 1175 patients. Cross-correlations of 23 subclasses of cytogenetic abnormalities were described. Childhood cases had higher incidences of normal karyotype, t(1;19), +8, 12q-, +21, +22 and high hyperdiploidy with 51-65 chromosomes, and lower incidences of t(9;22) and -5/5q- than adult ones (all pcytogenetic subclasses with immunophenotyping subgroups of ALL were studied. Our study presents the cytogenetic characteristics of a large series of Chinese ALL patients. Copyright © 2011 Elsevier Ltd. All rights reserved.