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Sample records for facilitate multicenter association

  1. Learned interval time facilitates associate memory retrieval

    PubMed Central

    van de Ven, Vincent; Kochs, Sarah; Smulders, Fren; De Weerd, Peter

    2017-01-01

    The extent to which time is represented in memory remains underinvestigated. We designed a time paired associate task (TPAT) in which participants implicitly learned cue–time–target associations between cue–target pairs and specific cue–target intervals. During subsequent memory testing, participants showed increased accuracy of identifying matching cue–target pairs if the time interval during testing matched the implicitly learned interval. A control experiment showed that participants had no explicit knowledge about the cue–time associations. We suggest that “elapsed time” can act as a temporal mnemonic associate that can facilitate retrieval of events associated in memory. PMID:28298554

  2. A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Gerdtsson, Anna S.; Malats, Núria; Säll, Anna; Real, Francisco X.; Porta, Miquel; Skoog, Petter; Persson, Helena; Wingren, Christer; Borrebaeck, Carl A. K.

    2015-01-01

    Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91–100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis. PMID:26587286

  3. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand

    PubMed Central

    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A.; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting. PMID:26629810

  4. The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

    PubMed Central

    White, Daniel K.; Neogi, Tuhina; Zhang, Yuqing; Felson, David; LaValley, Michael; Niu, Jingbo; Nevitt, Michael; Lewis, Cora E.; Torner, James; Douglas Gross, K.

    2012-01-01

    Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9 ± 3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain. PMID:22645666

  5. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

    PubMed Central

    2012-01-01

    Introduction CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis. PMID:22531499

  6. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

    PubMed Central

    Skolasky, Richard L.; Seaberg, Eric; Munro, Cynthia; Becker, James T.; Martin, Eileen; Ragin, Ann; Levine, Andrew; Miller, Eric

    2016-01-01

    Objective: To evaluate the frequency of HIV-associated neurocognitive disorder (HAND) in HIV+ individuals and determine whether the frequency of HAND changed over 4 years of follow-up. Methods: The Multicenter AIDS Cohort Study (MACS) is a prospective study of gay/bisexual men. Beginning in 2007, all MACS participants received a full neuropsychological test battery and functional assessments every 2 years to allow for HAND classification. Results: The frequency of HAND for the 364 HIV+ individuals seen in 2007–2008 was 33% and for the 197 HIV+ individuals seen at all time periods during the 2007–2008, 2009–2010, and 2011–2012 periods were 25%, 25%, and 31%, respectively. The overall frequency of HAND increased from 2009–2010 to 2011–2012 (p = 0.048). Over the 4-year study, 77% of the 197 HIV+ individuals remained at their same stage, with 13% showing deterioration and 10% showing improvement in HAND stage. Hypercholesterolemia was associated with HAND progression. A diagnosis of asymptomatic neurocognitive impairment was associated with a 2-fold increased risk of symptomatic HAND compared to a diagnosis of normal cognition. Conclusion: HAND remains common in HIV+ individuals. However, for the majority of HIV+ individuals on combination antiretroviral therapy with systemic virologic suppression, the diagnosis of HAND is not a progressive condition over 4 years of follow-up. Future studies should evaluate longitudinal changes in HAND and specific neurocognitive domains over a longer time period. PMID:26718568

  7. Reward association facilitates distractor suppression in human visual search.

    PubMed

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance.

  8. Brazilian multicenter study on prevalence of preterm birth and associated factors

    PubMed Central

    2010-01-01

    Background The occurrence of preterm birth remains a complex public health condition. It is considered the main cause of neonatal morbidity and mortality, resulting in a high likelihood of sequelae in surviving children. With variable incidence in several countries, it has grown markedly in the last decades. In Brazil, however, there are still difficulties to estimate its real occurrence. Therefore, it is essential to establish the prevalence and causes of this condition in order to propose prevention actions. This study intend to collect information from hospitals nationwide on the prevalence of preterm births, their associated socioeconomic and environmental factors, diagnostic and treatment methods resulting from causes such as spontaneous preterm labor, prelabor rupture of membranes, and therapeutic preterm birth, as well as neonatal results. Methods/Design This proposal is a multicenter cross-sectional study plus a nested case-control study, to be implemented in 27 reference obstetric centers in several regions of Brazil (North: 1; Northeast: 10; Central-west: 1; Southeast: 13; South: 2). For the cross sectional component, the participating centers should perform, during a period of six months, a prospective surveillance of all patients hospitalized to give birth, in order to identify preterm birth cases and their main causes. In the first three months of the study, an analysis of the factors associated with preterm birth will also be carried out, comparing women who have preterm birth with those who deliver at term. For the prevalence study, 37,000 births will be evaluated (at term and preterm), corresponding to approximately half the deliveries of all participating centers in 12 months. For the case-control study component, the estimated sample size is 1,055 women in each group (cases and controls). The total number of preterm births estimated to be followed in both components of the study is around 3,600. Data will be collected through a questionnaire all

  9. Prospective multicenter assessment of perioperative and minimum 2-year postoperative complication rates associated with adult spinal deformity surgery.

    PubMed

    Smith, Justin S; Klineberg, Eric; Lafage, Virginie; Shaffrey, Christopher I; Schwab, Frank; Lafage, Renaud; Hostin, Richard; Mundis, Gregory M; Errico, Thomas J; Kim, Han Jo; Protopsaltis, Themistocles S; Hamilton, D Kojo; Scheer, Justin K; Soroceanu, Alex; Kelly, Michael P; Line, Breton; Gupta, Munish; Deviren, Vedat; Hart, Robert; Burton, Douglas C; Bess, Shay; Ames, Christopher P

    2016-07-01

    OBJECTIVE Although multiple reports have documented significant benefit from surgical treatment of adult spinal deformity (ASD), these procedures can have high complication rates. Previously reported complications rates associated with ASD surgery are limited by retrospective design, single-surgeon or single-center cohorts, lack of rigorous data on complications, and/or limited follow-up. Accurate definition of complications associated with ASD surgery is important and may serve as a resource for patient counseling and efforts to improve the safety of patient care. The authors conducted a study to prospectively assess the rates of complications associated with ASD surgery with a minimum 2-year follow-up based on a multicenter study design that incorporated standardized data-collection forms, on-site study coordinators, and regular auditing of data to help ensure complete and accurate reporting of complications. In addition, they report age stratification of complication rates and provide a general assessment of factors that may be associated with the occurrence of complications. METHODS As part of a prospective, multicenter ASD database, standardized forms were used to collect data on surgery-related complications. On-site coordinators and central auditing helped ensure complete capture of complication data. Inclusion criteria were age older than 18 years, ASD, and plan for operative treatment. Complications were classified as perioperative (within 6 weeks of surgery) or delayed (between 6 weeks after surgery and time of last follow-up), and as minor or major. The primary focus for analyses was on patients who reached a minimum follow-up of 2 years. RESULTS Of 346 patients who met the inclusion criteria, 291 (84%) had a minimum 2-year follow-up (mean 2.1 years); their mean age was 56.2 years. The vast majority (99%) had treatment including a posterior procedure, 25% had an anterior procedure, and 19% had a 3-column osteotomy. At least 1 revision was required in 82

  10. Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients: A Multicenter Observational Study.

    PubMed

    Leveziel, Nicolas; Ragot, Stéphanie; Gand, Elise; Lichtwitz, Olivier; Halimi, Jean Michel; Gozlan, Julien; Gourdy, Pierre; Robert, Marie-Françoise; Dardari, Dured; Boissonnot, Michèle; Roussel, Ronan; Piguel, Xavier; Dupuy, Olivier; Torremocha, Florence; Saulnier, Pierre-Jean; Maréchaud, Richard; Hadjadj, Samy

    2015-08-01

    Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77-7.74; P = 0.0012) and of 4.29 (95% CI, 2.79-6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.

  11. A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

    PubMed Central

    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

    2015-01-01

    BACKGROUND 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. METHODS 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. RESULTS 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 < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION PTEN status assessed by FISH is an independent predictor for recurrence-free survival in

  12. Multicenter study on the prognosis associated with respiratory support for children with acute hypoxic respiratory failure.

    PubMed

    Guo, Fei; Hao, Lin; Zhen, Qing; Diao, Min; Zhang, Chonglin

    2016-11-01

    The objective of the present study was to explore the factors influencing the outcomes related to respiratory support of children with acute hypoxic respiratory failure (AHRF) in 30 hospitals. This was a non-controlled prospective and collaborative multicenter clinical study conducted from June, 2010 to May, 2011 (each hospital for 12 consecutive months). Children aged from 29 days to 6 years and who met the diagnostic standards of AHRF were enrolled as subjects for the study. After patients were enrolled, general parameters including disease diagnosis, treatment and prognosis were recorded. Then we analyzed the differences in prognosis and respiratory therapy of patients with AHRF. During the study period, 13,906 cases of AHRF were admitted among the 30 hospitals, accounting for 75.3% of the total number of patients with AHRF. The proportion in different hospitals ranged from 16 to 98%. A total of 492 children with hypoxic respiratory failure were admitted among the 30 hospitals. The prevalence rate was 3.54%, and the incidence of AHRF in each hospital was 4.54%. Tidal volume and respiratory support treatment were compared with the results from a 2006 study, and the differences were statistically significant in positive end-expiratory pressure (5 vs. 4, P=0.018), fraction of inspire O2 (0.5 vs. 0.4, P<0.001), pressure of artery O2 (70 vs. 60 mmHg, P<0.001) and peak inspiratory pressure (20 vs. 24 cm H2Ο, P<0.001). In conclusion, academic background and the level of regional economic development are factors which influence the prognosis of children with AHRF. On the basis of unapparent differences between academic background and the level of regional economic development, there is a substantial difference in the prognosis from different forms of respiratory support management for AHRF. Therefore, it is essential to develop respiratory support and the level of critical management of pediatric intensive care units.

  13. Visual outcomes in children with neurofibromatosis type 1-associated optic pathway glioma following chemotherapy: a multicenter retrospective analysis.

    PubMed

    Fisher, Michael J; Loguidice, Michael; Gutmann, David H; Listernick, Robert; Ferner, Rosalie E; Ullrich, Nicole J; Packer, Roger J; Tabori, Uri; Hoffman, Robert O; Ardern-Holmes, Simone L; Hummel, Trent R; Hargrave, Darren R; Bouffet, Eric; Charrow, Joel; Bilaniuk, Larissa T; Balcer, Laura J; Liu, Grant T

    2012-06-01

    Optic pathway gliomas (OPGs) occur in 15%-20% of children with neurofibromatosis type 1 (NF1); up to half become symptomatic. There is little information regarding ophthalmologic outcomes after chemotherapy. A retrospective multicenter study was undertaken to evaluate visual outcomes following chemotherapy for NF1-associated OPG, to identify risks for visual loss, and to ascertain indications for treatment. Subjects included children undergoing initial treatment for OPGs with chemotherapy between January 1997 and December 2007. Of 115 subjects, visual acuity (VA) decline and tumor progression were the primary reasons to initiate treatment, although there were significant differences in the pattern of indications cited among the institutions. Eighty-eight subjects and 168 eyes were evaluable for VA outcome. At completion of chemotherapy, VA improved (32% of subjects), remained stable (40%), or declined (28%). Tumor location was the most consistent prognostic factor for poor VA outcome. There was poor correlation between radiographic and VA outcomes. Although visual outcomes for NF1-associated OPG are not optimal, approximately one-third of children regain some vision with treatment. Since radiographic outcomes do not predict visual outcomes, their use as the primary measure of treatment success is in question. The lack of consensus regarding the indications for treatment underlines the need for better standardization of care. Future clinical trials for OPG require standardized visual assessment methods and clear definitions of visual outcomes.

  14. Facilitated processing of visual stimuli associated with the body.

    PubMed

    Whiteley, Louise; Kennett, Steffan; Taylor-Clarke, Marisa; Haggard, Patrick

    2004-01-01

    Recent work on tactile perception has revealed enhanced tactile acuity and speeded spatial-choice reaction times (RTs) when viewing the stimulated body site as opposed to viewing a neutral object. Here we examine whether this body-view enhancement effect extends to visual targets. Participants performed a speeded spatial discrimination between two lights attached either to their own left index finger or to a wooden finger-shaped object, making a simple distal--proximal decision. We filmed either the finger-mounted or the object-mounted lights in separate experimental blocks and the live scene was projected onto a screen in front of the participants. Thus, participants responded to identical visual targets varying only in their context: on the body or not. Results revealed a large performance advantage for the finger-mounted stimuli: reaction times were substantially reduced, while discrimination accuracy was unaffected. With this finding we address concerns associated with previous work on the processing of stimuli attributed to the self and extend the finding of a performance advantage for such stimuli to vision.

  15. High protein intake is associated with low prevalence of frailty among old Japanese women: a multicenter cross-sectional study

    PubMed Central

    2013-01-01

    Background Protein intake has been inversely associated with frailty. However, no study has examined the effect of the difference of protein sources (animal or plant) or the amino acid composing the protein on frailty. Therefore, we examined the association of protein and amino acid intakes with frailty among elderly Japanese women. Methods A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 prefectures of Japan. Intakes of total, animal, and plant protein and eight selected amino acids were estimated from a validated brief-type self-administered diet history questionnaire and amino acid composition database. Frailty was defined as the presence of three or more of the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss. Results The number of subjects with frailty was 481 (23%). Adjusted ORs (95% CI) for frailty in the first, second, third, fourth, and fifth quintiles of total protein intake were 1.00 (reference), 1.02 (0.72, 1.45), 0.64 (0.45, 0.93), 0.62 (0.43, 0.90), and 0.66 (0.46, 0.96), respectively (P for trend = 0.001). Subjects categorized to the third, fourth, and fifth quintiles of total protein intake (>69.8 g/d) showed significantly lower ORs than those to the first quintile (all P <0.03). The intakes of animal and plant protein and all selected amino acids were also inversely associated with frailty (P for trend <0.04), with the multivariate adjusted OR in the highest compared to the lowest quintile of 0.73 for animal protein and 0.66 for plant protein, and 0.67-0.74 for amino acids, albeit that the ORs for these dietary variables were less marked than those for total protein. Conclusions Total protein intake was significantly inversely associated with frailty in elderly Japanese women. The association of total protein with

  16. Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

    PubMed Central

    Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik

    2017-01-01

    Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp. PMID:28178337

  17. Assessment of the Asian Neurogastroenterology and Motility Association Chronic Constipation Criteria: An Asian Multicenter Cross-sectional Study

    PubMed Central

    Gwee, Kok-Ann; Bergmans, Paul; Kim, JinYong; Coudsy, Bogdana; Sim, Angelia; Chen, Minhu; Lin, Lin; Hou, Xiaohua; Wang, Huahong; Goh, Khean-Lee; Pangilinan, John A; Kim, Nayoung; des Varannes, Stanislas Bruley

    2017-01-01

    Background/Aims There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. Methods This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator’s judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. Results The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator’s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. Conclusion This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC. PMID:27764907

  18. Factors associated with complicated erosive esophagitis: A Japanese multicenter, prospective, cross-sectional study

    PubMed Central

    Sakaguchi, Masahiro; Manabe, Noriaki; Ueki, Nobuo; Miwa, Jun; Inaba, Tomoki; Yoshida, Norimasa; Sakurai, Kouichi; Nakagawa, Masahiro; Yamada, Hajime; Saito, Michiya; Nakada, Koji; Iwakiri, Katsuhiko; Joh, Takashi; Haruma, Ken

    2017-01-01

    AIM To assess the clinical characteristics of patients with complicated erosive esophagitis (EE) and their associated factors. METHODS This prospective, cross-sectional study included patients diagnosed with EE by upper gastrointestinal endoscopy between October 2014 and March 2015 at 106 Japanese hospitals. Data on medical history, general condition, gastrointestinal symptoms, lifestyle habits, comorbidities, and endoscopic findings were collected using a standard form to create a dedicated database. Logistic regression analysis was used to calculate adjusted odds ratios (aOR) and 95%CI for the association with complicated EE. RESULTS During the study period, 1749 patients diagnosed with EE, 38.3% of whom were prescribed proton pump inhibitors (PPIs) were included. Of them, 143 (8.2%) had EE complications. Esophageal bleeding occurred in 84 (4.8%) patients, esophageal strictures in 45 (2.6%) patients, and 14 (0.8%) patients experienced both. Multivariate analysis showed that increased age (aOR: 1.05; 95%CI: 1.03-1.08), concomitant use of psychotropic agents (aOR: 6.51; 95%CI: 3.01-13.61), and Los Angeles grades B (aOR: 2.69; 95%CI: 1.48-4.96), C (aOR: 15.38; 95%CI: 8.62-28.37), and D (aOR: 71.49; 95%CI: 37.47-142.01) were significantly associated with complications, whereas alcohol consumption 2-4 d/wk was negatively associated (aOR: 0.23; 95%CI: 0.06-0.61). Analyzing associated factors with each EE complication separately showed esophageal ulcer bleeding were associated with increased age (aOR: 1.05; 95%CI: 1.02-1.07) and Los Angeles grades B (aOR: 3.60; 95%CI: 1.52-8.50), C (aOR: 27.61; 95%CI: 12.34-61.80), and D (aOR: 119.09; 95%CI: 51.15-277.29), while esophageal strictures were associated with increased age (aOR: 1.07; 95%CI: 1.04-1.10), gastroesophageal reflux symptom (aOR: 2.51; 95%CI: 1.39-4.51), concomitant use of psychotropic agents (aOR: 11.79; 95%CI: 5.06-27.48), Los Angeles grades C (aOR: 7.35; 95%CI: 3.32-16.25), and D (aOR: 20.34; 95%CI: 8

  19. Barriers and Facilitators Associated with Non-Surgical Treatment Use for Osteoarthritis Patients in Orthopaedic Practice

    PubMed Central

    Hofstede, Stefanie N.; Marang-van de Mheen, Perla J.; Vliet Vlieland, Thea P. M.; van den Ende, Cornelia H. M.; Nelissen, Rob G. H. H.; van Bodegom-Vos, Leti

    2016-01-01

    Introduction International evidence-based guidelines for the management of patients with hip and knee osteoarthritis (OA) recommend to start with (a combination of) non-surgical treatments, and using surgical intervention only if a patient does not respond sufficiently to non-surgical treatment options. Despite these recommendations, there are strong indications that non-surgical treatments are not optimally used in orthopaedic practice. To improve the adoption of non-surgical treatments, more insight is needed into barriers and facilitators of these treatments. Therefore, this study assessed which barriers and facilitators are associated with the use and prescription of different non-surgical treatments before hip and knee OA in orthopaedic practice among patients and orthopaedic surgeons in the Netherlands. Materials and Methods We performed two internet-based surveys among 172 orthopaedic surgeons and 174 OA patients. Univariate association and multivariable regression techniques are used to identify barriers and facilitators associated with the use of non-surgical treatments. Results Most barriers and facilitators among patients were associated with the use of physical therapy, lifestyle advice and dietary therapy. Among orthopaedic surgeons, most were associated with prescription of acetaminophen, dietary therapy and physical therapy. Examples of barriers and facilitators among patients included “People in my environment had positive experiences with a surgery” (facilitator for education about OA), and “Advice of people in my environment to keep on moving” (facilitator for lifestyle and dietary advice). For orthopaedic surgeons, examples were “Lack of knowledge about guideline” (barrier for lifestyle advice), “Agreements/ deliberations with primary care” and “Easy communication with a dietician” (facilitators for dietary therapy). Also the belief in the efficacy of these treatments was associated with increased prescription. Conclusions

  20. Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study

    PubMed Central

    Nagata, Naoyoshi; Niikura, Ryota; Yamada, Atsuo; Sakurai, Toshiyuki; Shimbo, Takuro; Kobayashi, Yuka; Okamoto, Makoto; Mitsuno, Yuzo; Ogura, Keiji; Hirata, Yoshihiro; Fujimoto, Kazuma; Akiyama, Junichi; Uemura, Naomi; Koike, Kazuhiko

    2016-01-01

    Background Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs. Methods In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use. Results In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545). Conclusions One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs

  1. Multicenter European Prevalence Study of Neurocognitive Impairment and Associated Factors in HIV Positive Patients.

    PubMed

    Haddow, Lewis J; Laverick, Rosanna; Daskalopoulou, Marina; McDonnell, Jeffrey; Lampe, Fiona C; Gilson, Richard; Speakman, Andrew; Antinori, Andrea; Balestra, Pietro; Bruun, Tina; Gerstoft, Jan; Nielsen, Lars; Vassilenko, Anna; Collins, Simon; Rodger, Alison J

    2017-01-31

    We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤-1 in at least 2 out of 5 cognitive domains. Participants' mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm(3); 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54-0.94) or with a university education (aPR 0.72, 95% CI 0.54-0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09-2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03-1.90).

  2. The Use of a Sequenced Questioning Paradigm to Facilitate Associative Fluency in Preschoolers.

    ERIC Educational Resources Information Center

    Pellegrini, A. D.; Greene, Helen

    The extent to which free play versus sequenced questioning conditions facilitates preschoolers' associative fluency was investigated in this study. Twenty-four children (12 boys and 12 girls, with a mean age of 50.7 months) were randomly assigned to one of three conditions: free play, sequenced questioning, and control. In the sequenced…

  3. Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

    PubMed Central

    López Furst, María José; de Vedia, Lautaro; Fernández, Silvina; Gardella, Noella; Ganaha, María Cristina; Prieto, Sergio; Carbone, Edith; Lista, Nicolás; Rotryng, Flavio; Morera, Graciana I.; Mollerach, Marta; Stryjewski, Martín E.

    2013-01-01

    Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Materials and Methods Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina. PMID:24324543

  4. CraA, a Major Facilitator Superfamily Efflux Pump Associated with Chloramphenicol Resistance in Acinetobacter baumannii▿

    PubMed Central

    Roca, I.; Marti, S.; Espinal, P.; Martínez, P.; Gibert, I.; Vila, J.

    2009-01-01

    Acinetobacter baumannii has been increasingly associated with hospital-acquired infections, and the presence of multidrug resistance strains is of great concern to clinicians. A. baumannii is thought to possess a great deal of intrinsic resistance to several antimicrobial agents, including chloramphenicol, although the mechanisms involved in such resistance are not well understood. In this work, we have identified a major facilitator superfamily efflux pump present in most A. baumannii strains, displaying strong substrate specificity toward chloramphenicol. PMID:19581458

  5. HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation.

    PubMed

    Park, Jihye; Lammers, Fabienne; Herr, Winship; Song, Ji-Joon

    2012-10-23

    Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1(N) and HCF-1(C) subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.

  6. Central amygdala GluA1 facilitates associative learning of opioid reward.

    PubMed

    Cai, You-Qing; Wang, Wei; Hou, Yuan-Yuan; Zhang, Zhi; Xie, Jun; Pan, Zhizhong Z

    2013-01-23

    GluA1 subunits of AMPA glutamate receptors are implicated in the synaptic plasticity induced by drugs of abuse for behaviors of drug addiction, but GluA1 roles in emotional learning and memories of drug reward in the development of drug addiction remain unclear. In this study of the central nucleus of the amygdala (CeA), which is critical in emotional learning of drug reward, we investigated how adaptive changes in the expression of GluA1 subunits affected the learning process of opioid-induced context-reward association (associative learning) for the acquisition of reward-related behavior. In CeA neurons, we found that CeA GluA1 expression was significantly increased 2 h after conditioning treatment with morphine, but not 24 h after the conditioning when the behavior of conditioned place reference (CPP) was fully established in rats. Adenoviral overexpression of GluA1 subunits in CeA accelerated associative learning, as shown by reduced minimum time of morphine conditioning required for CPP acquisition and by facilitated CPP extinction through extinction training with no morphine involved. Adenoviral shRNA-mediated downregulation of CeA GluA1 produced opposite effects, inhibiting the processes of both CPP acquisition and CPP extinction. Adenoviral knockdown of CeA GluA2 subunits facilitated CPP acquisition, but did not alter CPP extinction. Whole-cell recording revealed enhanced electrophysiological properties of postsynaptic GluA2-lacking AMPA receptors in adenoviral GluA1-infected CeA neurons. These results suggest that increased GluA1 expression of CeA AMPA receptors facilitates the associative learning of context-drug reward, an important process in both development and relapse of drug-seeking behaviors in drug addiction.

  7. Fibroblast miR-210 overexpression is independently associated with clinical failure in Prostate Cancer – a multicenter (in situ hybridization) study

    PubMed Central

    Andersen, Sigve; Richardsen, Elin; Moi, Line; Donnem, Tom; Nordby, Yngve; Ness, Nora; Holman, Marte Eilertsen; Bremnes, Roy M.; Busund, Lill-Tove

    2016-01-01

    There is a need for better prognostication in prostate cancer (PC). “The micromanager of hypoxia”, microRNA-210 (miR-210) is directly linked to hypoxia, is overexpressed in PC and has been implied in tumor cell-fibroblast crosstalk. We investigated the prognostic impact of miR-210 in tumor cells and fibroblasts in PC. Tumor and stromal samples from a multicenter PC cohort of 535 prostatectomy patients were inserted into tissue microarrays. To investigate the expression of miR-210, we used in situ hybridization and two pathologists semiquantitatively scored its expression. Overexpression of miR-210 in tumor cells was not associated to biochemical failure-free survival (BFFS, p = 0.85) or clinical failure-free survival (CFFS, p = 0.09). However, overexpression of miR-210 in fibroblasts was significantly associated to a poor CFFS (p = 0.001), but not BFFS (p = 0.232). This feature was validated in both cohorts. Overexpression of miR-210 was independently associated with a reduced CFFS (HR = 2.76, CI 95% 1.25–6.09, p = 0.012). Overexpression of miR-210 in fibroblasts is independently associated with a poor CFFS. This highlights the importance of fibroblasts and cellular compartment crosstalk in PC. miR-210 is a candidate prognostic marker and potential therapeutic target in PC. PMID:27824162

  8. Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

    PubMed Central

    Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

    2014-01-01

    Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

  9. The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP)

    PubMed Central

    Souza, Renato T.; Cecatti, Jose G.; Passini, Renato; Tedesco, Ricardo P.; Lajos, Giuliane J.; Nomura, Marcelo L.; Rehder, Patricia M.; Dias, Tabata Z.; Haddad, Samira M.; Pacagnella, Rodolfo C.; Costa, Maria L.

    2016-01-01

    Background About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. Methods and Findings This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02–13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57–35.88), multiple

  10. Competition and facilitation between the marine nitrogen-fixing cyanobacterium Cyanothece and its associated bacterial community.

    PubMed

    Brauer, Verena S; Stomp, Maayke; Bouvier, Thierry; Fouilland, Eric; Leboulanger, Christophe; Confurius-Guns, Veronique; Weissing, Franz J; Stal, LucasJ; Huisman, Jef

    2014-01-01

    N2-fixing cyanobacteria represent a major source of new nitrogen and carbon for marine microbial communities, but little is known about their ecological interactions with associated microbiota. In this study we investigated the interactions between the unicellular N2-fixing cyanobacterium Cyanothece sp. Miami BG043511 and its associated free-living chemotrophic bacteria at different concentrations of nitrate and dissolved organic carbon and different temperatures. High temperature strongly stimulated the growth of Cyanothece, but had less effect on the growth and community composition of the chemotrophic bacteria. Conversely, nitrate and carbon addition did not significantly increase the abundance of Cyanothece, but strongly affected the abundance and species composition of the associated chemotrophic bacteria. In nitrate-free medium the associated bacterial community was co-dominated by the putative diazotroph Mesorhizobium and the putative aerobic anoxygenic phototroph Erythrobacter and after addition of organic carbon also by the Flavobacterium Muricauda. Addition of nitrate shifted the composition toward co-dominance by Erythrobacter and the Gammaproteobacterium Marinobacter. Our results indicate that Cyanothece modified the species composition of its associated bacteria through a combination of competition and facilitation. Furthermore, within the bacterial community, niche differentiation appeared to play an important role, contributing to the coexistence of a variety of different functional groups. An important implication of these findings is that changes in nitrogen and carbon availability due to, e.g., eutrophication and climate change are likely to have a major impact on the species composition of the bacterial community associated with N2-fixing cyanobacteria.

  11. Is there an association between prior anti-inflammatory drug exposure and occurrence of peritonsillar abscess (PTA)? A national multicenter prospective observational case-control study.

    PubMed

    Lepelletier, D; Pinaud, V; Le Conte, P; Bourigault, C; Asseray, N; Ballereau, F; Caillon, J; Ferron, C; Righini, C; Batard, E; Potel, G

    2017-01-01

    The aim of this study was to evaluate whether recent systemic anti-inflammatory agents (AIAs) exposure in patients with sore throat managed with or without antibiotic therapy influenced the risk of peritonsillar abscess (PTA). We conducted a multicenter case-control study in 13 French university hospitals in 2009-2012 comparing patients admitted with PTA to matched controls: patients with sore throat but without PTA who were followed up for 10 days after visiting their primary-care physician. In the multivariate stepwise logistic regression model comparing 120 cases with PTA to 143 controls, factors significantly associated with PTA were male gender (odds ratio [OR], 2.0; p = 0.03), smoking (OR, 2.0; p = 0.03), and prior self-medication with systemic AIAs (OR, 3.5; p = 0.01). Topical treatment was associated with significant protection against PTA (OR, 0.3; p < 0.001). In conclusion, self-medication with systemic AIAs appears to be an independent factor associated with the occurrence of PTA. This is an important message as non-steroidal AIAs access is favored by their over-counter availability in pharmacies. This finding must be interpreted with caution due to the study design and a prospective, randomized study is needed to substantiate these possible causal risk factors.

  12. Sibling Facilitation Mediates the Association Between Older and Younger Sibling Alcohol Use in Late Adolescence

    PubMed Central

    Samek, Diana R.; McGue, Matt; Keyes, Margaret; Iacono, William G.

    2014-01-01

    Previous research has shown adolescent siblings are similar in their alcohol use and that this similarity is largely due to their shared environment. Using a genetically-informed sibling sample (196 full-biological pairs, 384 genetically unrelated pairs), we confirmed that the extent to which older siblings facilitate younger siblings’ alcohol use (i.e., help them get alcohol) was one factor contributing to this shared environmental association. All analyses controlled for parent and peer influences. Findings were not moderated by sibling differences in genetic relatedness, gender, or ethnicity. Proximity in sibling age strengthened these associations, somewhat. Results were especially strong for sibling pairs where the older sibling was of legal drinking age. Implications for prevention and intervention are discussed. PMID:26640355

  13. Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis

    PubMed Central

    2012-01-01

    Background Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. Findings Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. Conclusions The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting

  14. Complication rates associated with 3-column osteotomy in 82 adult spinal deformity patients: retrospective review of a prospectively collected multicenter consecutive series with 2-year follow-up.

    PubMed

    Smith, Justin S; Shaffrey, Christopher I; Klineberg, Eric; Lafage, Virginie; Schwab, Frank; Lafage, Renaud; Kim, Han Jo; Hostin, Richard; Mundis, Gregory M; Gupta, Munish; Liabaud, Barthelemy; Scheer, Justin K; Diebo, Bassel G; Protopsaltis, Themistocles S; Kelly, Michael P; Deviren, Vedat; Hart, Robert; Burton, Doug; Bess, Shay; Ames, Christopher P

    2017-02-17

    OBJECTIVE Although 3-column osteotomy (3CO) can provide powerful alignment correction in adult spinal deformity (ASD), these procedures are complex and associated with high complication rates. The authors' objective was to assess complications associated with ASD surgery that included 3CO based on a prospectively collected multicenter database. METHODS This study is a retrospective review of a prospectively collected multicenter consecutive case registry. ASD patients treated with 3CO and eligible for 2-year follow-up were identified from a prospectively collected multicenter ASD database. Early (≤ 6 weeks after surgery) and delayed (> 6 weeks after surgery) complications were collected using standardized forms and on-site coordinators. RESULTS Of 106 ASD patients treated with 3CO, 82 (77%; 68 treated with pedicle subtraction osteotomy [PSO] and 14 treated with vertebral column resection [VCR]) had 2-year follow-up (76% women, mean age 60.7 years, previous spine fusion in 80%). The mean number of posterior fusion levels was 12.9, and 17% also had an anterior fusion. A total of 76 early (44 minor, 32 major) and 66 delayed (13 minor, 53 major) complications were reported, with 41 patients (50.0%) and 45 patients (54.9%) affected, respectively. Overall, 64 patients (78.0%) had at least 1 complication, and 50 (61.0%) had at least 1 major complication. The most common complications were rod breakage (31.7%), dural tear (20.7%), radiculopathy (9.8%), motor deficit (9.8%), proximal junctional kyphosis (PJK, 9.8%), pleural effusion (8.5%), and deep wound infection (7.3%). Compared with patients who did not experience early or delayed complications, those who had these complications did not differ significantly with regard to age, sex, body mass index, Charlson Comorbidity Index, American Society of Anesthesiologists score, smoking status, history of previous spine surgery or spine fusion, or whether the 3CO performed was a PSO or VCR (p ≥ 0.06). Twenty-seven (33

  15. Prevention of NSAID-associated gastroduodenal injury in healthy volunteers-a randomized, double-blind, multicenter study comparing DA-9601 with misoprostol.

    PubMed

    Lee, Kang Nyeong; Lee, Oh Young; Choi, Myung-Gyu; Choi, Seok Reyol; Lee, Dong Ho; Lee, Yong Chan; Kim, Tae Nyeun; Choi, Suck Chei; Rew, Jong Sun; Seol, Sang-Yong

    2011-08-01

    In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

  16. Association between the p.Thr1406Asn polymorphism of the carbamoyl-phosphate synthetase 1 gene and necrotizing enterocolitis: A prospective multicenter study

    PubMed Central

    Moonen, Rob M.; Cavallaro, Giacomo; Huizing, Maurice J.; González-Luis, Gema E.; Mosca, Fabio; Villamor, Eduardo

    2016-01-01

    The p.Thr1406Asn (rs1047891) polymorphism of the carbamoyl-phosphate synthetase 1 (CPS1) gene has been linked to functional consequences affecting the downstream availability of the nitric oxide precursor L-arginine. L-arginine concentrations are decreased in preterm infants with necrotizing enterocolitis (NEC). In this multicenter prospective study, we investigated the association of the p.Thr1406Asn polymorphism with NEC in 477 preterm infants (36 cases of NEC) from 4 European neonatal intensive care units (Maastricht, Las Palmas de Gran Canaria, Mantova, and Milan). Allele and genotype frequencies of the p.Thr1406Asn polymorphism did not significantly differ between the infants with and without NEC. In contrast, the minor A-allele was significantly less frequent in the group of 64 infants with the combined outcome NEC or death before 34 weeks of corrected gestational age than in the infants without the outcome (0.20 vs. 0.31, P = 0.03). In addition, a significant negative association of the A-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.54, 95% CI 0.29–0.99) and the additive (aOR 0.58, 95% CI 0.36–0.93) genetic models. In conclusion, our study provides further evidence that a functional variant of the CPS1 gene may contribute to NEC susceptibility. PMID:27833157

  17. Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

    PubMed Central

    Lee, Kang Nyeong; Lee, Oh Young; Choi, Myung-Gyu; Choi, Seok Reyol; Lee, Dong Ho; Lee, Yong Chan; Kim, Tae Nyeun; Choi, Suck Chei; Rew, Jong Sun

    2011-01-01

    In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 µg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects. PMID:21860559

  18. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2014-10-01

    AD_________________ Award Number: W81XWH-10-1-0894 TITLE: Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration...DATES COVERED 15 Sep 2013 - 14 Sep 2014 4. TITLE AND SUBTITLE Multicenter Clinical Trial of Keratin Biomaterial for 5a. CONTRACT NUMBER Peripheral...has developed a keratin biomaterial hydrogel that can be used as luminal filler in nerve guidance conduits to facilitate nerve regeneration

  19. DNA barcoding facilitates associations and diagnoses for Trichoptera larvae of the Churchill (Manitoba, Canada) area

    PubMed Central

    2013-01-01

    Background The North American Trichoptera larvae are poorly known at the species level, despite their importance in the understanding of freshwater fauna and critical use in biomonitoring. This study focused on morphological diagnoses for larvae occurring in the Churchill, Manitoba area, representing the largest larval association effort for the caddisflies at any given locality thus far. The current DNA barcode reference library of Trichoptera (available on the Barcode of Life Data Systems) was utilized to provide larval-adult associations. Results The present study collected an additional 23 new species records for the Churchill area, increasing the total Trichoptera richness to 91 species. We were able to associate 62 larval taxa, comprising 68.1% of the Churchill area Trichoptera taxa. This endeavor to identify immature life stage for the caddisflies enabled the development of morphological diagnoses, production of photographs and an appropriate taxonomic key to facilitate larval species analyses in the area. Conclusions The use of DNA for associations of unknown larvae with known adults proved rapid and successful. This method should accelerate the state-of-knowledge for North American Trichoptera larvae as well as other taxonomic lineages. The morphological analysis should be useful for determination of material from the Churchill area. PMID:23425021

  20. Cerebral Activity Associated with Transient Sleep-Facilitated Reduction in Motor Memory Vulnerability to Interference

    PubMed Central

    Albouy, Geneviève; King, Bradley R.; Schmidt, Christina; Desseilles, Martin; Dang-Vu, Thien Thanh; Balteau, Evelyne; Phillips, Christophe; Degueldre, Christian; Orban, Pierre; Benali, Habib; Peigneux, Philippe; Luxen, André; Karni, Avi; Doyon, Julien; Maquet, Pierre; Korman, Maria

    2016-01-01

    Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories. PMID:27725727

  1. Cerebral Activity Associated with Transient Sleep-Facilitated Reduction in Motor Memory Vulnerability to Interference.

    PubMed

    Albouy, Geneviève; King, Bradley R; Schmidt, Christina; Desseilles, Martin; Dang-Vu, Thien Thanh; Balteau, Evelyne; Phillips, Christophe; Degueldre, Christian; Orban, Pierre; Benali, Habib; Peigneux, Philippe; Luxen, André; Karni, Avi; Doyon, Julien; Maquet, Pierre; Korman, Maria

    2016-10-11

    Motor memory consolidation is characterized, in part, by a sleep-facilitated decrease in susceptibility to subsequent interfering experiences. Surprisingly, the cerebral substrates supporting this phenomenon have never been examined. We used fMRI to investigate the neural correlates of the influence of sleep on interference to motor memory consolidation. Healthy young adults were trained on a sequential motor task, and subsequently practiced a second competing sequence after an interval including diurnal sleep or wakefulness. Participants were then retested on the initial sequence 8 h and 24 h (including nocturnal sleep) after training. Results demonstrated that a post-training nap significantly protected memory against interference at 8 h and modulated the link between cerebral activity and behavior, such that a smaller post-interference decrease in cortico-striatal activity was associated with better performance. Interestingly, the protective effect of a nap was only transitory, as both groups performed similarly at 24 h. Activity in cortico-striatal areas that was disrupted during the day, presumably due to interference and accentuated in the absence of a nap, was restored overnight. Altogether, our findings offer the first evidence that cortico-striatal areas play a critical role in the transient sleep-facilitated reduction in motor memory vulnerability and in the overnight restoration of previously degraded memories.

  2. A Cross-sectional Study of the Association Between Chronic Hepatitis C Virus Infection and Subclinical Coronary Atherosclerosis Among Participants in the Multicenter AIDS Cohort Study

    PubMed Central

    McKibben, Rebeccah A.; Haberlen, Sabina A.; Post, Wendy S.; Brown, Todd T.; Budoff, Matthew; Witt, Mallory D.; Kingsley, Lawrence A.; Palella, Frank J.; Thio, Chloe L.; Seaberg, Eric C.

    2016-01-01

    Background. Hepatitis C virus (HCV) infection may increase the risk of cardiovascular disease (CVD). We evaluated the association of chronic HCV infection and coronary atherosclerosis among participants in the Multicenter AIDS Cohort Study. Methods. We assessed 994 men with or without human immunodeficiency virus (HIV) infection (87 of whom had chronic HCV infection) for coronary plaque, using noncontrast coronary computed tomography (CT); 755 also underwent CT angiography. We then evaluated the associations of chronic HCV infection and HIV infection with measures of plaque prevalence, extent, and stenosis. Results. After adjustment for demographic characteristics, HIV serostatus, behaviors, and CVD risk factors, chronic HCV infection was significantly associated with a higher prevalence of coronary artery calcium (prevalence ratio, 1.29; 95% confidence interval [CI], 1.02–1.63), any plaque (prevalence ratio, 1.26; 95% CI, 1.09–1.45), and noncalcified plaque (prevalence ratio, 1.42; 95% CI, 1.16–1.75). Chronic HCV infection and HIV infection were independently associated with the prevalence of any plaque and of noncalcified plaque, but there was no evidence of a synergistic effect due to HIV/HCV coinfection. The prevalences of coronary artery calcium, any plaque, noncalcified plaque, a mixture of noncalcified and calcified plaque, and calcified plaque were significantly higher among men with an HCV RNA load of ≥2 × 106 IU/mL, compared with findings among men without chronic HCV infection. Conclusions. Chronic HCV infection is associated with subclinical CVD, suggesting that vigilant assessments of cardiovascular risk are warranted for HCV-infected individuals. Future research should determine whether HCV infection duration or HCV treatment influence coronary plaque development. PMID:26216904

  3. Implementation of Departmental Quality Strategies Is Positively Associated with Clinical Practice: Results of a Multicenter Study in 73 Hospitals in 7 European Countries

    PubMed Central

    2015-01-01

    Background Given the amount of time and resources invested in implementing quality programs in hospitals, few studies have investigated their clinical impact and what strategies could be recommended to enhance its effectiveness. Objective To assess variations in clinical practice and explore associations with hospital- and department-level quality management systems. Design Multicenter, multilevel cross-sectional study. Setting and Participants Seventy-three acute care hospitals with 276 departments managing acute myocardial infarction, deliveries, hip fracture, and stroke in seven countries. Intervention None. Measures Predictor variables included 3 hospital- and 4 department-level quality measures. Six measures were collected through direct observation by an external surveyor and one was assessed through a questionnaire completed by hospital quality managers. Dependent variables included 24 clinical practice indicators based on case note reviews covering the 4 conditions (acute myocardial infarction, deliveries, hip fracture and stroke). A directed acyclic graph was used to encode relationships between predictors, outcomes, and covariates and to guide the choice of covariates to control for confounding. Results and Limitations Data were provided on 9021 clinical records by 276 departments in 73 hospitals. There were substantial variations in compliance with the 24 clinical practice indicators. Weak associations were observed between hospital quality systems and 4 of the 24 indicators, but on analyzing department-level quality systems, strong associations were observed for 8 of the 11 indicators for acute myocardial infarction and stroke. Clinical indicators supported by higher levels of evidence were more frequently associated with quality systems and activities. Conclusions There are significant gaps between recommended standards of care and clinical practice in a large sample of hospitals. Implementation of department-level quality strategies was significantly

  4. Association between Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study (GEMS) and Types of Handwashing Materials Used by Caretakers in Mirzapur, Bangladesh

    PubMed Central

    Baker, Kelly K.; Dil Farzana, Fahmida; Ferdous, Farzana; Ahmed, Shahnawaz; Kumar Das, Sumon; Faruque, A. S. G.; Nasrin, Dilruba; Kotloff, Karen L.; Nataro, James P.; Kolappaswamy, Krishnan; Levine, Myron M.

    2014-01-01

    Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62–1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children. PMID:24778193

  5. Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial

    PubMed Central

    2014-01-01

    Background Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. Methods/design To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. Discussion The results of this study will provide a new strategy to help relieve AIMSS. Trial registration ISCTN: ISRCTN06129599 (assigned 14 August 2013). PMID:24885324

  6. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  7. Randomized Multicenter Trial of the Effects of Melanoma-Associated Helper Peptides and Cyclophosphamide on the Immunogenicity of a Multipeptide Melanoma Vaccine

    PubMed Central

    Slingluff, Craig L.; Petroni, Gina R.; Chianese-Bullock, Kimberly A.; Smolkin, Mark E.; Ross, Merrick I.; Haas, Naomi B.; von Mehren, Margaret; Grosh, William W.

    2011-01-01

    Purpose This multicenter randomized trial was designed to test whether melanoma-associated helper peptides augment CD8+ T-cell responses to a melanoma vaccine and whether cyclophosphamide (CY) pretreatment augments CD4+ or CD8+ T-cell responses to that vaccine. Patients and Methods In all, 167 eligible patients with resected stage IIB to IV melanoma were randomly assigned to four vaccination study arms. Patients were vaccinated with 12 class I major histocompatibility complex–restricted melanoma peptides (12MP) to stimulate CD8+ T cells and were randomly assigned to receive a tetanus helper peptide or a mixture of six melanoma-associated helper peptides (6MHP) to stimulate CD4+ T cells. Before vaccination, patients were also randomly assigned to receive CY pretreatment or not. T-cell responses were assessed by an ex vivo interferon gamma ELISpot assay. Clinical outcomes and toxicities were recorded. Results Vaccination with 12MP plus tetanus induced CD8+ T-cell responses in 78% of patients and CD4+ T-cell responses to tetanus peptide in 93% of patients. Vaccination with 12MP plus 6MHP induced CD8+ responses in 19% of patients and CD4+ responses to 6MHP in 48% of patients. CY had no significant effect on T-cell responses. Overall 3-year survival was 79% (95% CI, 71% to 86%), with no significant differences (at this point) by study arm. Conclusion Melanoma-associated helper peptides paradoxically decreased CD8+ T-cell responses to a melanoma vaccine (P < .001), and CY pretreatment had no immunologic or clinical effect. Prior work showed immunologic and clinical activity of 6MHP alone. Possible explanations for negative effects on CD8 responses include modulation of homing receptor expression or induction of antigen-specific regulatory T cells. PMID:21690475

  8. Ant association facilitates the evolution of diet breadth in a lycaenid butterfly

    PubMed Central

    Forister, Matthew L.; Gompert, Zachariah; Nice, Chris C.; Forister, Glen W.; Fordyce, James A.

    2011-01-01

    The role of mutualistic interactions in adaptive diversification has not been thoroughly examined. Lycaenid butterflies provide excellent systems for exploring mutualistic interactions, as more than half of this family is known to use ants as a resource in interactions that range from parasitism to mutualism. We investigate the hypothesis that protection from predators offered to caterpillars by ants might facilitate host-range evolution. Specifically, experiments with the butterfly Lycaeides melissa investigated the role of ant association in the use of a novel host, alfalfa, Medicago sativa, which is a sub-optimal host for larval development. Survival on alfalfa is increased by the presence of ants, thus supporting the hypothesis that interaction with ants might be important for host-range evolution. Using a demographic model to explore ecological conditions associated with host-range expansion in L. melissa, we conclude that the presence of ants might be an essential component for populations persisting on the novel, sub-optimal host. PMID:21047856

  9. Parenteral Nutrition–Associated Hyperglycemia in Non–Critically Ill Inpatients Increases the Risk of In-Hospital Mortality (Multicenter Study)

    PubMed Central

    Olveira, Gabriel; Tapia, María José; Ocón, Julia; Cabrejas-Gómez, Carmen; Ballesteros-Pomar, María D.; Vidal-Casariego, Alfonso; Arraiza-Irigoyen, Carmen; Olivares, Josefina; Conde-García, Maria del Carmen; García-Manzanares, Álvaro; Botella-Romero, Francisco; Quílez-Toboso, Rosa P.; Cabrerizo, Lucio; Matia, Pilar; Chicharro, Luisa; Burgos, Rosa; Pujante, Pedro; Ferrer, Mercedes; Zugasti, Ana; Prieto, Javier; Diéguez, Marta; Carrera, María José; Vila-Bundo, Anna; Urgelés, Juan Ramón; Aragón-Valera, Carmen; Rovira, Adela; Bretón, Irene; García-Peris, Pilar; Muñoz-Garach, Araceli; Márquez, Efren; del Olmo, Dolores; Pereira, José Luis; Tous, María C.

    2013-01-01

    OBJECTIVE Hyperglycemia may increase mortality in patients who receive total parenteral nutrition (TPN). However, this has not been well studied in noncritically ill patients (i.e., patients in the nonintensive care unit setting). The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality. RESULTS The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47–21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA1c levels. CONCLUSIONS Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality. PMID:23223407

  10. Multicenter study of street foods in 13 towns on four continents by the food and environmental hygiene study group of the international network of pasteur and associated institutes.

    PubMed

    Garin, B; Aïdara, A; Spiegel, A; Arrive, P; Bastaraud, A; Cartel, J L; Aissa, R Ben; Duval, P; Gay, M; Gherardi, C; Gouali, M; Karou, T G; Kruy, S L; Soares, J L; Mouffok, F; Ravaonindrina, N; Rasolofonirina, N; Pham, M T; Wouafo, M; Catteau, M; Mathiot, C; Mauclere, P; Rocourt, J

    2002-01-01

    An international multicenter study of ready-to-eat foods, sandwiches, and ice creams or sorbets sold in the streets and their vendors was carried out to assess the microbiological quality of these foods and to identify characteristics of the vendors possibly associated with pathogens. Thirteen towns in Africa, America, Asia, and Oceania were involved in the study. A single protocol was used in all 13 centers: representative sampling was by random selection of vendors and a sample of foods bought from each of these vendors at a time and date selected at random. Microbiological analyses were carried out using standardized Association Française de Normalisation methods, and the use of a standardized questionnaire to collect data concerning the characteristics of the vendors. Fifteen surveys were carried out, with 3,003 food samples from 1,268 vendors. The proportion of unsatisfactory food samples was between 12.7 and 82.9% for ice creams and sorbets and between 11.3 and 92% for sandwiches. For ice creams and sorbets, the sale of a large number of units (>80 per day) increased the risk of unsatisfactory food by a factor of 2.8 (95% confidence interval [CI]: 1.5 to 5.1), lack of training in food hygiene by 6.6 (95% CI: 1.1 to 50). and by a factor of 2.8 (95% CI: 1.4 to 5.4) for mobile vendors. These risk factors were not identified for sandwiches, this difference may be due to the presence of a cooking step in their preparation. These results show that the poor microbiological quality of these street foods constitutes a potential hazard to public health, that the extent of this hazard varies between the cities studied, and that vendors' health education in food safety is a crucial factor in the prevention of foodborne infections.

  11. Low Dose Parenteral Soybean Oil for the Prevention of Parenteral Nutrition Associated Liver Disease in Neonates with Gastrointestinal Disorders: a Multi-Center Randomized Controlled Pilot Study

    PubMed Central

    Calkins, Kara L.; Havranek, Thomas; Kelley-Quon, Lorraine I.; Cerny, Laura; Flores, Martiniano; Grogan, Tristan; Shew, Stephen B.

    2015-01-01

    Background Neonates with gastrointestinal disorders (GD) are at high risk for parenteral nutrition associated liver disease (PNALD). Soybean-based intravenous lipid emulsions (S-ILE) have been associated with PNALD. This study’s objective was to determine if a lower dose when compared to a higher dose of S-ILE prevents cholestasis without compromising growth. Material and Methods This multi-center randomized controlled pilot study enrolled subjects with GD who were ≤ 5 days of age to a low dose (approximately 1 g/kg/day) (LOW) or control dose of S-ILE (approximately 3 g/kg/day) (CON). The primary outcome was cholestasis (direct bilirubin (DB) > 2 mg/dL) after the first seven days of age. Secondary outcomes included growth, PN duration, and late onset sepsis. Results Baseline characteristics were similar between the LOW (n=20) and CON groups (n=16). When the LOW group was compared to the CON group, there was no difference in cholestasis (30% vs. 38%, p=0.7) or secondary outcomes. However, mean (±SE) DB rate of change over the first eight weeks (0.07±0.04 vs. 0.3±0.09 mg/dL/week, p=0.01) and entire study (0.008±0.03 vs. 0.2±0.07 mg/dL/week, p=0.02) was lower in the LOW group when compared to the CON group. Conclusion In neonates with GD who received a lower dose of S-ILE, DB increased at a slower rate in comparison to neonates who received a higher dose of S-ILE. Growth was comparable between the groups. This study demonstrates a need for a larger, randomized controlled trial comparing two different S-ILE doses for cholestasis prevention in neonates at risk for PNALD. PMID:26024828

  12. Epicardial Fat is Associated with Duration of Antiretroviral Therapy and Coronary Atherosclerosis: The Multicenter AIDS Cohort Study

    PubMed Central

    Brener, Michael; Ketlogetswe, Kerunne; Budoff, Matthew; Jacobson, Lisa P.; Li, Xiuhong; Rezaeian, Panteha; Razipour, Aryabod; Palella, Frank J; Kingsley, Lawrence; Witt, Mallory D; George, Richard T; Post, Wendy S

    2014-01-01

    Objective Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis. Design We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men. Methods We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus. Results HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusions Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV. PMID:24809732

  13. Graphics Processing Unit-Based Bioheat Simulation to Facilitate Rapid Decision Making Associated with Cryosurgery Training.

    PubMed

    Keelan, Robert; Zhang, Hong; Shimada, Kenji; Rabin, Yoed

    2016-04-01

    This study focuses on the implementation of an efficient numerical technique for cryosurgery simulations on a graphics processing unit as an alternative means to accelerate runtime. This study is part of an ongoing effort to develop computerized training tools for cryosurgery, with prostate cryosurgery as a developmental model. The ability to perform rapid simulations of various test cases is critical to facilitate sound decision making associated with medical training. Consistent with clinical practice, the training tool aims at correlating the frozen region contour and the corresponding temperature field with the target region shape. The current study focuses on the feasibility of graphics processing unit-based computation using C++ accelerated massive parallelism, as one possible implementation. Benchmark results on a variety of computation platforms display between 3-fold acceleration (laptop) and 13-fold acceleration (gaming computer) of cryosurgery simulation, in comparison with the more common implementation on a multicore central processing unit. While the general concept of graphics processing unit-based simulations is not new, its application to phase-change problems, combined with the unique requirements for cryosurgery optimization, represents the core contribution of the current study.

  14. Incontinence-associated skin damage in nursing home residents: a secondary analysis of a prospective, multicenter study.

    PubMed

    Zimmaro Bliss, Donna; Zehrer, Cindy; Savik, Kay; Thayer, Debra; Smith, Graham

    2006-12-01

    More than half of the nursing home population is incontinent of urine or feces, presenting challenges to perineal skin health. To determine the occurrence and severity of skin damage in nursing home residents with incontinence, a secondary analysis of data collected from a multisite, open-label, quasi-experimental study of cost and efficacy of four regimens for preventing incontinence-associated dermatitis in nursing home residents was performed. Sixteen randomly selected nursing homes from across the US were included in the study. Participating nursing home residents were incontinent of urine and/or feces and free of skin damage. Of the 1,918 persons screened, 51% (n = 981) qualified for prospective surveillance. Perineal skin was assessed over a 6-week period; frequency, type, and severity of skin damage were observed. Skin damage developed after a median of 13 (range 6 to 42) days in 45 out of 981 residents (4.6%), of which 3.4% was determined to be incontinence-associated dermatitis. Some residents (14 out of 45, 31%) had incontinence-associated dermatitis of other skin damage in more than one area. This study is one of the first to report the characteristics of incontinence-associated dermatitis in a large sample of nursing home residents. The sample size and random selection of nursing homes impart generalizability to the findings. Incontinence-associated dermatitis is a risk in nursing home residents, especially those with fecal incontinence. These findings suggest that the rate and severity of incontinence-associated dermatitis are low with close monitoring and use of a defined skin care regimen that includes a pH-balanced cleanser and moisture barrier.

  15. Prenatal stress as a modifier of associations between phthalate exposure and reproductive development: results from a multicenter pregnancy cohort study

    PubMed Central

    Barrett, Emily S.; Parlett, Lauren E.; Sathyanarayana, Sheela; Redmon, J. Bruce; Nguyen, Ruby H. N.; Swan, Shanna H.

    2015-01-01

    Background Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). Methods Phthalate metabolites (including those of diethylhexyl phthalate [DEHP] and their molar sum [∑DEHP]) were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as “lower” and “higher” stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress group) using adjusted multiple regression interaction models. Results In the lower stress group, first trimester ∑DEHP was inversely associated with two measures of male AGD: anoscrotal distance (AGD-AS; β=−1.78; 95% CI: −2.97, −0.59) and anopenile distance (AGD-AP; β=−1.61; 95% CI: −3.01, −0.22). By contrast, associations in the higher stress group were mostly positive and non-significant in male infants. No associations were observed in girls. Conclusions Associations between prenatal phthalate exposure and altered genital development were only apparent in sons of mothers who reported no SLEs during pregnancy. Prenatal stress and phthalates may interact to shape fetal development in ways that have not been previously explored. PMID:26576028

  16. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

    PubMed

    Myint, Thein; Anderson, Albert M; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W; Jhaveri, Malhar; Greenberg, Richard N; Bamberger, David M; Rodgers, Mark; Crawford, Timothy N; Wheat, L Joseph

    2014-01-01

    Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p < 0.0001) and 5% death (p = 0.28) in the PC group. Relapse occurred in 53% of the nonadherent patients but not in the adherent patients (p < 0.0001). Sixty-seven percent of patients with initial central nervous system (CNS) histoplasmosis relapsed compared to 15% of patients without CNS involvement (p = 0.0004), which may be accounted for by nonadherence. In addition, patients with antigenuria above 2.0 ng/mL at 1-year follow-up were 12.82 times (95% confidence interval, 2.91-55.56) more likely to relapse compared to those with antigenuria below 2.0 ng/mL. Discontinuation of antifungal therapy was safe in adherent patients who completed at least 1 year of antifungal treatment, and had CD4 counts >150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

  17. Progression of renal damage in glycogen storage disease type I is associated to hyperlipidemia: a multicenter prospective Italian study.

    PubMed

    Melis, Daniela; Cozzolino, Mariarosaria; Minopoli, Giorgia; Balivo, Francesca; Parini, Rossella; Rigoldi, Miriam; Paci, Sabrina; Dionisi-Vici, Carlo; Burlina, Alberto; Andria, Generoso; Parenti, Giancarlo

    2015-04-01

    Angiotensin converting enzyme (ACE)-inhibitors decrease glomerular hyperfiltration but not microalbuminuria and proteinuria in glycogen storage disease type I. In the current study, we demonstrated that severe hyperlipidemia is associated with ACE-inhibitor ineffectiveness. We underline the importance of adequate metabolic control in glycogen storage disease type I. A combination therapy with ACE-inhibitors and lipid lowering drugs might be considered.

  18. Association of a 62 Variant Type 2 Diabetes Genetic Risk Score with Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study

    PubMed Central

    Dauriz, Marco; Porneala, Bianca C.; Guo, Xiuqing; Bielak, Lawrence F.; Peyser, Patricia A.; Durant, Nefertiti H.; Carnethon, Mercedes R.; Bonadonna, Riccardo C.; Bonora, Enzo; Bowden, Donald W.; Florez, Jose C.; Fornage, Myriam; Hivert, Marie-France; Jacobs, David R.; Kabagambe, Edmond K.; Lewis, Cora E.; Murabito, Joanne M.; Rasmussen-Torvik, Laura J.; Rich, Stephen S.; Vassy, Jason L.; Yao, Jie; Carr, Jeffrey J.; Kardia, Sharon L.R.; Siscovick, David; O'Donnell, Christopher J.; Rotter, Jerome I.; Dupuis, Josée; Meigs, James B.

    2015-01-01

    Background Type 2 diabetes (T2D) and cardiovascular disease (CVD) share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results In a cross-sectional analysis including up to 9,210 European Americans, 3,773 African Americans, 1,446 Hispanic Americans and 773 Chinese Americans without known CVD and enrolled in the FHS, CARDIA, MESA and GENOA studies, we tested a 62 T2D-loci genetic risk score (GRS62) for association with measures of SCA, including coronary artery (CACS) or abdominal aortic calcium score, common (CCA-IMT) and internal carotid artery intima-media thickness, and ankle-brachial index (ABI). We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors adjusted model (significance = p<0.01 = 0.05/5, number of traits analyzed). An inverse association with CACS in MESA Europeans (fully-adjusted p=0.004) and with CCA-IMT in FHS (p=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance sub-GRS in FHS and CARDIA. Conclusions SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and CVD risk loci. PMID:25805414

  19. THE ASSOCIATION BETWEEN PHYSIOLOGIC DEAD-SPACE FRACTION AND MORTALITY IN PATIENTS WITH THE ACUTE RESPIRATORY DISTRESS SYNDROME ENROLLED INTO A PROSPECTIVE MULTI-CENTERED CLINICAL TRIAL

    PubMed Central

    Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D.; Calfee, Carolyn S.; Matthay, Michael A

    2014-01-01

    Objective To test the association between pulmonary dead-space fraction (VD/VT) and mortality in patients with ARDS (Berlin Definition, PaO2/FiO2 ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. Design Prospective, multi-center study. Setting Medical-surgical intensive care units in the United States. Subjects 126 ALI patients enrolled into a phase III randomized, placebo-controlled study of aerosolized albuterol. Interventions None Measurements and Main Results VD/VT and pulmonary mechanics were measured within 4 hours of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend towards higher VD/VT compared to survivors (0.62 ± 0.11 vs. 0.56 ± 0.11 respectively, p = 0.08). Differences in VD/VT between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs. 0.55 ± 0.11 respectively, p = 0.01) and 2 (0.67 ± 0.12 vs. 0.56 ± 0.11 respectively, p=0.004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in VD/VT [95% confidence interval]: 6.84 [1.62–28.84] p = 0.01; and study day 2: 4.90 [1.28–18.73] p = 0.02) after adjusting for VD/VT, PaO2/FiO2, oxygenation index, vasopressor use and the primary risk for ARDS. Using a Cox proportional hazard model, VD/VT was associated with a trend towards higher mortality (HR = 4.37 [CI: 0.99 – 19.32]; p = 0.052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI: 1.12 – 3.35] p = 0.04). Conclusions Markedly elevated VD/VT (≥ 0.60) in early ARDS is associated with higher mortality. Measuring VD/VT may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. PMID:24381187

  20. Enterovirus 71 Virion-Associated Galectin-1 Facilitates Viral Replication and Stability

    PubMed Central

    Lee, Pei-Huan; Liu, Chia-Ming; Ho, Tzong-Shiann; Tsai, Yi-Che; Lin, Chi-Cheng; Wang, Ya-Fang; Chen, Yuh-Ling; Yu, Chun-Keung; Wang, Shih-Min; Liu, Ching-Chuan; Shiau, Ai-Li; Lei, Huan-Yao; Chang, Chih-Peng

    2015-01-01

    Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children’s health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells.Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection. PMID:25706563

  1. Characterization of community-associated Staphylococcus aureus from skin and soft-tissue infections: a multicenter study in China.

    PubMed

    Liu, Ying; Xu, Zhe; Yang, Zhou; Sun, Juan; Ma, Lin

    2016-12-21

    We evaluated the epidemiological and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children and adult patients with skin and soft-tissue infections (SSTIs) in China. Prospective community-acquired S. aureus SSTI surveillance was conducted in 23 hospitals over a 24-month period. Susceptibility to 16 antimicrobials was evaluated using the agar dilution method. StatApriori was used to determine statistically significant association trends. The genotypic characteristics of CA-MRSA isolates were tested by staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing, and multilocus sequence typing. The presence of Panton-Valentine leukocidin (pvl) genes was determined. Overall, 71.6% (1946/2716) of cases were community-associated S. aureus. CA-MRSA accounted for 2.6% (51). Out of 1895 methicillin-sensitive S. aureus strains, 97.3% were resistant to erythromycin, 96.6% to penicillin and 89.1% to clindamycin. No S. aureus strains were resistant to vancomycin. Thirteen sequence types (STs) and 17 spa types were detected among the CA-MRSA strains. The most prevalent sequence type was ST121 (19/51, 37.3%), followed by ST59 (13/51, 25.5%). In addition, t437 was predominant, accounting for 43.1% (22/51). Only five (9.8%) of the CA-MRSA strains harbored pvl genes. There were no significant differences in antibiotic sensitivity profiles between ST121 and non-ST121 MRSA isolates. However, ST121 strains tended to be more resistant to cefazolin, whereas non-ST121 strains were more resistant to chloramphenicol. In conclusion, CA-MRSA infections are rare among Chinese SSTI patients. MRSA strains in China have diverse genetic backgrounds, with ST121 being the predominant clone. Fusidic acid and mupirocin remain effective for topical treatment.

  2. Association between levonorgestrel emergency contraception and the risk of ectopic pregnancy: a multicenter case-control study

    PubMed Central

    Zhang, Jian; Li, Cheng; Zhao, Wei-Hong; Xi, Xiaowei; Cao, Shu-Jun; Ping, Hua; Qin, Guo-Juan; Cheng, Linan; Huang, He-Feng

    2015-01-01

    Cases of ectopic pregnancy (EP) following levonorgestrel emergency contraception (LNG-EC) failure have been reported continuously, but whether there is an association between EP risk and LNG-EC is unclear. We concluded a case-control study to explore this association by recruiting 2,411 EP patients as case group, and 2,416 women with intrauterine pregnancy and 2,419 non-pregnant women as control groups. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated and adjusted for potential confounding factors. Previous use of LNG-EC was not correlated with the EP. Compared to women who did not use contraceptives, current use of LNG-EC reduced the risk for intrauterine pregnancy (Adjusted OR [AOR] = 0.20, 95%CI: 0.14–0.27), but did not increase the risk for EP (AOR2 = 1.04, 95%CI: 0.76–1.42). Furthermore, compared to women who did not have further act of intercourse, women with unprotected further act of intercourse were at a higher risk of EP (AOR1 = 2.35, 95%CI: 1.17–4.71), and women with repeated use of LNG-EC for further intercourse during the same cycle was also associated with a higher risk for EP (AOR1 = 3.08, 95%CI: 1.09–8.71; AOR2 = 2.49, 95%CI: 1.00–6.19). A better understanding of the risk of EP following LNG-EC failure can optimize LNG-EC use and thus reduce the risk of EP. PMID:25674909

  3. Characterization of community-associated Staphylococcus aureus from skin and soft-tissue infections: a multicenter study in China

    PubMed Central

    Liu, Ying; Xu, Zhe; Yang, Zhou; Sun, Juan; Ma, Lin

    2016-01-01

    We evaluated the epidemiological and molecular features of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and methicillin-sensitive S. aureus (MSSA) from children and adult patients with skin and soft-tissue infections (SSTIs) in China. Prospective community-acquired S. aureus SSTI surveillance was conducted in 23 hospitals over a 24-month period. Susceptibility to 16 antimicrobials was evaluated using the agar dilution method. StatApriori was used to determine statistically significant association trends. The genotypic characteristics of CA-MRSA isolates were tested by staphylococcal cassette chromosome mec (SCCmec) typing, staphylococcal protein A (spa) typing, and multilocus sequence typing. The presence of Panton–Valentine leukocidin (pvl) genes was determined. Overall, 71.6% (1946/2716) of cases were community-associated S. aureus. CA-MRSA accounted for 2.6% (51). Out of 1895 methicillin-sensitive S. aureus strains, 97.3% were resistant to erythromycin, 96.6% to penicillin and 89.1% to clindamycin. No S. aureus strains were resistant to vancomycin. Thirteen sequence types (STs) and 17 spa types were detected among the CA-MRSA strains. The most prevalent sequence type was ST121 (19/51, 37.3%), followed by ST59 (13/51, 25.5%). In addition, t437 was predominant, accounting for 43.1% (22/51). Only five (9.8%) of the CA-MRSA strains harbored pvl genes. There were no significant differences in antibiotic sensitivity profiles between ST121 and non-ST121 MRSA isolates. However, ST121 strains tended to be more resistant to cefazolin, whereas non-ST121 strains were more resistant to chloramphenicol. In conclusion, CA-MRSA infections are rare among Chinese SSTI patients. MRSA strains in China have diverse genetic backgrounds, with ST121 being the predominant clone. Fusidic acid and mupirocin remain effective for topical treatment. PMID:27999423

  4. Evidence of sleep-facilitating effect on formation of novel semantic associations: an event-related potential (ERP) study.

    PubMed

    Lin, Chun-Cheng; Yang, Chien-Ming

    2014-12-01

    Paired-associates learning of unrelated words can reflect the formation of a new association in the semantic network. Research results on the facilitating effect of sleep on unrelated word-pair associates learning remain contradictory. The behavioral measures used in previous studies may not have been sensitive enough to reflect the process of new word association during sleep. The present study used the N400 component of event-related potential (ERP) to further assess the facilitating effect of sleep on the formation of new semantic associations. Thirty subjects were randomly assigned to either the Sleep group or the Wakefulness group. After paired-associates learning and pre-test, they underwent nocturnal sleep and sleep deprivation, respectively. A post-test was conducted after the subjects had one night of recovery sleep. ERPs were recorded during both test phases. Behavioral data showed significant differences in improvements in recognition and decreases in reaction time from pre-test to post-test between the Sleep and Wakefulness groups. The N400 peak amplitude attenuated significantly after sleep, but not after wakefulness. These results suggest that sleep has a facilitating effect on the formation of novel associations. Unexpectedly, slow wave sleep was negatively correlated with improvement in recognition during the post-test but was positively correlated with the number of word-pairs acquired during the learning phase. This may the result of a ceiling effect limiting the improvement achieved in subjects who learned better during the learning phase.

  5. A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical Intensive Care Units

    PubMed Central

    Smithburger, Pamela L.; Buckley, Mitchell S.; Culver, Mark A.; Sokol, Sarah; Lat, Ishaq; Handler, Steven M.; Kirisci, Levent; Kane-Gill, Sandra L.

    2016-01-01

    Objective Prior research indicates off-label use is common in the intensive care unit (ICU); however the safety of off-label use has not been assessed. The study objective was to determine the incidence of adverse drug reactions (ADRs) associated with off-label use and evaluate off-label use as a risk factor for the development of ADRs in an adult ICU population. Setting Medical ICUs at three academic medical centers Patients Adult patients (age ≥ 18 years old) receiving medication therapy Interventions All administered medications were evaluated for Food and Drug Administration (FDA) approved or off-label use. Patients were assessed daily for the development of an ADR through active surveillance. Three ADR assessment instruments were used to determine the probability of an ADR resulting from drug therapy. Severity and harm of the ADR were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of ADRs. Measurements and Main Results Overall, 1654 patient days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen ADRs were categorized dichotomously (FDA or off-label), with 56% and 44% being associated with FDA approved and off-label use, respectively. The number of ADRs for medications administered and number of harmful and severe ADRs did not differ for medications used for FDA approved or off-label use (0.74% vs 0.67%, p = 0.336; 33 vs. 31 events, p=0.567; 24 vs. 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of ADRs increases by 8% for every one additional off-label medication (HR = 1.08; 95 % CI: 1.018–1.154). Conclusion While ADRs do not occur more frequently with off-label use, ADR risk increases with each additional off-label medication used. PMID:25855897

  6. Lack of Association Found between Helicobacter pylori Infection and Diarrhea-Predominant Irritable Bowel Syndrome: A Multicenter Retrospective Study

    PubMed Central

    Xiong, Feng; Xiong, Man; Ma, Zonghui; Huang, Senxiong; Li, Aimin

    2016-01-01

    Aims. The association between Helicobacter pylori (H. pylori) infection and diarrhea-predominant irritable bowel syndrome (IBS-D) is still controversial. Here we performed a retrospective study to explore this issue. Methods. A total of 502 inpatients with Rome III confirmed IBS-D and known H. pylori status from 8 hospitals were enrolled. H. pylori-positive patients, hospitalized in the recent year, were followed up to evaluate the effects of H. pylori eradication on IBS-D clinical course. Results. Of the 502 IBS-D patients, 206 were H. pylori-positive, with an infection rate that has no significant difference with that of the general population in Guangdong province (p = 0.348). For patients followed up, no significant differences were noted as to overall symptoms (p = 0.562), abdominal pain/discomfort (p = 0.777), bloating (p = 0.736), stool frequency (p = 0.835), or stool characteristics (p = 0.928) between the H. pylori-eradicated group and the control group. The results were the same in long-term follow-up patients except the improvement of bloating, which showed that the bloating score in the H. pylori-eradicated group was significantly lower (p = 0.047). Conclusions. No significant correlation between H. pylori infection and IBS-D was noted. Overall, IBS-D patients may not benefit from H. pylori eradication. PMID:27493660

  7. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial

    PubMed Central

    Ozawa, Hideki; Uemura, Naomi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the 13C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), 13C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  8. The Association between Life Satisfaction and the Extent of Depression, Anxiety and Stress among Iranian Nurses: A Multicenter Survey

    PubMed Central

    Yazdanshenas Ghazwin, Manijeh; Kavian, Mohammad; Ahmadloo, Mohsen; Jarchi, Alemeh; Golchin Javadi, Shaghayegh; Latifi, Sahar; Ghajarzadeh, Mahsa

    2016-01-01

    Objective: The determinants of satisfaction of life (SWL) are poorly described among Iranian employed nurses. This study aimed to assess the effect of various factors including age, gender, marital status, depression, anxiety and stress on SWL among Iranian nurses. Method: Employed nurses in three teaching hospitals were invited to participate in this study. Ninety-four nurses (65 women and 29 men) participated in this study. Depression, anxiety, stress scale (DASS-21) was used to measure the related variables. Satisfaction with Life Scale (SWLS) was used to assess SWL. Multivariate analysis was utilized to examine the relationship between multiple variables. Results: A noticeable proportion of Iranian employed nurses were either dissatisfied or extremely dissatisfied with life (45%). Severe depression was related to lower scores of SWLS (P: 0.001, r = −0.32). The similar outcomes were detected between anxiety and stress scales, and SWLS (P: 0.023, r = −0.23 and P: 0.008, r = −0.27 for anxiety and stress, respectively). Although females were more vulnerable to depression (P: 0.010) and stress (P: 0.013), the overall effect of gender on SWL was insignificant (0.41). Satisfactions with financial power and work environment were associated with higher scores of SWLS (P: 0.030 and 0.042, respectively). Marital status was not related to severity of depression, anxiety, stress and SWLS (P: 0.39, 0.38, 0.80, and 0.61, respectively). Conclusion: This study revealed that poor satisfaction with financial status and work environment, depression, anxiety and stress are the major determinants of satisfaction with life among Iranian employed nurses. PMID:27437009

  9. Age-Associated Perceptions of Physical Activity Facilitators and Barriers Among Women in Rural Southernmost Illinois

    PubMed Central

    Carnahan, Leslie R.; Peacock, Nadine R.

    2016-01-01

    Introduction Women living in rural areas in the United States experience disproportionately high rates of diseases such as obesity and heart disease and are less likely than women living in urban areas to meet daily physical activity (PA) recommendations. The purpose of our research was to understand age-specific perceptions of barriers and facilitators to rural women engaging in PA and to identify strategies to promote PA among these women. Methods As part of a community health assessment to learn about women’s health issues, 110 adult women participated in 14 focus groups. The women were divided into 4 age groups, and focus groups were held in various community settings. We used qualitative analysis methods to explore themes in the women’s narratives, including themes related to PA knowledge, PA behavior, and access to PA facilities. Results Participants described multiple and often conflicting individual, social, and environmental barriers and facilitators to PA. Several barriers and facilitators were shared across age groups (eg, competing priorities and inadequate knowledge about PA’s role in disease prevention and disease management). Other barriers (eg, illness and injury) and facilitators (eg, PA as a social opportunity) differed by age group. Conclusion Rural women in southernmost Illinois have often contradictory barriers and facilitators to PA, and those barriers and facilitators are different at different points in a woman’s life. Our findings suggest the need for multilevel, multisector approaches to promote PA. Additionally, this research supports the need for tailored PA promotion programs for rural women to address the barriers these women face across their lifespan. PMID:27685431

  10. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

    SciTech Connect

    Anacak, Yavuz; Miller, Robert C.; Constantinou, Nikos; Mamusa, Angela M.; Epelbaum, Ron; Li Yexiong; Calduch, Anna Lucas; Kowalczyk, Anna; Weber, Damien C.; Kadish, Sidney P.; Poortmans, Philip; Kamer, Serra; Ozsahin, Mahmut

    2012-01-01

    Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

  11. Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

    PubMed Central

    Kim, Sung-Bae; Lee, Jung Shin; Kim, Heung Tae; Im, Yong Hyuck; Kim, Tae Won; Ryoo, Baek Yeol; Park, Yeon Hee; Park, Joon Oh; Park, Keunchil; Katoh, Hitoshi; Yamamoto, Minoru

    2007-01-01

    Abstract Background: Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan. Objective: The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH. Methods: This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study. Results: Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1–23] and day 6, 5.5 [1–17

  12. Teacher Discussion Facilitation: A New Measure and Its Associations with Students' Perceived Understanding, Interest, and Engagement

    ERIC Educational Resources Information Center

    Finn, Amber N.; Schrodt, Paul

    2016-01-01

    Two studies were conducted to develop a low-inference, behavioral measure of teacher discussion facilitation in the college classroom. In Study 1 (N = 360), a pilot inventory was developed from extant research. In Study 2 (N = 360), confirmatory factor analyses supported the dimensional structure of the pilot inventory and yielded a new, Teacher…

  13. Association between serum levels of C-reactive protein and response to treatment of chemotherapy-induced anemia in patients with solid tumors: a multicenter, prospective, observational study.

    PubMed

    Esquerdo Galiana, Gaspar; Cervera, Jose Manuel; Barrajón, Enrique; Juárez, Asunción; Llorca, Cristina; Díaz, Nieves; López, Antonio; Peiró, Rafael

    2013-03-01

    Our objective was to determine the association between C-reactive protein (CRP) levels at initiation of anemia treatment and response in solid tumor patients with chemotherapy (CT)-induced anemia. This was a multicenter, prospective, observational study which included adult patients with solid tumor initiating treatment for CT-induced anemia. Data were collected up to 16 weeks, or until premature discontinuation. We included 98 patients (median age 62.5 years, 64 % males, 57 % with ECOG 0-1, 85.7 % at stages III-IV and 54.1 % undergoing palliative CT). Mean (SD) Hb levels at baseline were 10.3 (0.9) g/dL (85.7 % < 11 g/dL) and median (Q1; Q3) CRP was 16.4 mg/L (3.9; 77.8) (68 % ≥ 5 mg/L). A total of 96 % of patients initiated erythropoiesis-stimulating agents (ESA) and iron supplementation; 4 % initiated iron monotherapy. After a median of 85 days, 65 % of patients had Hb ≥ 11 g/dL (in absence of transfusion) (mean change: +0.86 g/dL, 95 % confidence interval (CI) 0.53-1.19). A total of 8 patients required transfusion. A significant correlation (r = -0.39, p = 0.003) was observed between baseline CRP and final Hb levels. In the multivariate linear regression analysis, the independent predictors of higher final Hb levels were a high baseline Hb (adjusted ß = +0.69 g/dL for each g/dL of baseline Hb, 95 % CI 0.17-1.21) and a low log baseline CRP (-0.62 for each log mg/L, 95 %CI -1.22 to -0.02). Our results suggest that, in patients with solid tumors and CT-induced anemia, high CRP levels at treatment initiation predict a poor response to treatment with ESA and iron, independently from anemia severity at therapy initiation and from other patient and disease characteristics.

  14. Learning-facilitated synaptic plasticity occurs in the intermediate hippocampus in association with spatial learning

    PubMed Central

    Kenney, Jana; Manahan-Vaughan, Denise

    2013-01-01

    The dorsoventral axis of the hippocampus is differentiated into dorsal, intermediate, and ventral parts. Whereas the dorsal part is believed to specialize in processing spatial information, the ventral may be equipped to process non-spatial information. The precise role of the intermediate hippocampus is unclear, although recent data suggests it is functionally distinct, at least from the dorsal hippocampus. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with robust synaptic plasticity (>24 h) when a spatial learning event is coupled with afferent stimulation that would normally not lead to a lasting plasticity response: in the dorsal hippocampus novel space facilitates robust expression of long-term potentiation (LTP), whereas novel spatial content facilitates long-term depression (LTD). We explored whether the intermediate hippocampus engages in this kind of synaptic plasticity in response to novel spatial experience. In freely moving rats, high-frequency stimulation at 200 Hz (3 bursts of 15 stimuli) elicited synaptic potentiation that lasted for at least 4 h. Coupling of this stimulation with the exploration of a novel holeboard resulted in LTP that lasted for over 24 h. Low frequency afferent stimulation (1 Hz, 900 pulses) resulted in short-term depression (STD) that was significantly enhanced and prolonged by exposure to a novel large orientational (landmark) cues, however LTD was not enabled. Exposure to a holeboard that included novel objects in the holeboard holes elicited a transient enhancement of STD of the population spike (PS) but not field EPSP, and also failed to facilitate the expression of LTD. Our data suggest that the intermediate dentate gyrus engages in processing of spatial information, but is functionally distinct to the dorsal dentate gyrus. This may in turn reflect their assumed different roles in synaptic information processing and memory formation. PMID:24194716

  15. Bolting multicenter solutions

    NASA Astrophysics Data System (ADS)

    Bena, Iosif; Bossard, Guillaume; Katmadas, Stefanos; Turton, David

    2017-01-01

    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.

  16. A Bayesian statistical analysis of behavioral facilitation associated with deep brain stimulation

    PubMed Central

    Smith, Anne C; Shah, Sudhin A; Hudson, Andrew E; Purpura, Keith P; Victor, Jonathan D; Brown, Emery N; Schiff, Nicholas D

    2009-01-01

    Deep brain stimulation (DBS) is an established therapy for Parkinson’s Disease and is being investigated as a treatment for chronic depression, obsessive compulsive disorder and for facilitating functional recovery of patients in minimally conscious states following brain injury. For all of these applications, quantitative assessments of the behavioral effects of DBS are crucial to determine whether the therapy is effective and, if so, how stimulation parameters can be optimized. Behavioral analyses for DBS are challenging because subject performance is typically assessed from only a small set of discrete measurements made on a discrete rating scale, the time course of DBS effects is unknown, and between-subject differences are often large. We demonstrate how Bayesian state-space methods can be used to characterize the relationship between DBS and behavior comparing our approach with logistic regression in two experiments: the effects of DBS on attention of a macaque monkey performing a reaction-time task, and the effects of DBS on motor behavior of a human patient in a minimally conscious state. The state-space analysis can assess the magnitude of DBS behavioral facilitation (positive or negative) at specific time points and has important implications for developing principled strategies to optimize DBS paradigms. PMID:19576932

  17. Modulation of presynaptic action potential kinetics underlies synaptic facilitation of type B photoreceptors after associative conditioning in Hermissenda.

    PubMed

    Gandhi, C C; Matzel, L D

    2000-03-01

    Descriptions of conditioned response generation in Hermissenda stipulate that the synaptic interaction between type B and A photoreceptors should be enhanced after associative pairings of light and rotation. Although evidence from several laboratories has confirmed this assumption, the mechanism underlying this synaptic facilitation has not been elucidated. Here we report that in vitro conditioning (i.e., light paired with stimulation of vestibular hair cells) modifies the kinetics of presynaptic action potentials in the B photoreceptor in a manner sufficient to account for this synaptic facilitation. After paired training, we observed an increase in the duration of evoked action potentials and a decrease in the amplitude of the spike afterhyperpolarization in the B-cell. As previously reported, paired training also enhanced the excitability (i.e., input resistance and evoked spike rate) of the B photoreceptor. In a second experiment, simultaneous recordings were made in type B and A photoreceptors, and paired training was found to produce an increase in the amplitude of the IPSP in the A photoreceptor in response to an evoked spike in the B-cell. Importantly, there was no change in the initial slope of the postsynaptic IPSP in the A photoreceptor, suggesting that spike duration-independent mechanisms of neurotransmitter exocytosis or postsynaptic receptor sensitivity did not contribute to the observed synaptic facilitation. Perfusion of 4-aminopyridine (4-AP) mimicked a known effect of behavioral conditioning in that it specifically reduced the amplitude of the transient voltage-dependent K(+) current (I(A)) in the B-cell, but in addition, produced action potential broadening and synaptic facilitation that was analogous to that observed after in vitro conditioning. Finally, the effect of 4-AP on B-cell action potentials and on the postsynaptic IPSP in the A-cell was occluded by previous paired (but not unpaired) training, suggesting that the prolongation of the B

  18. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  19. Determining Barriers and Facilitators Associated With Willingness to Use a Personal Health Information Management System to Support Worksite Wellness Programs.

    PubMed

    Neyens, David M; Childers, Ashley Kay

    2016-01-05

    Purpose . To determine the barriers and facilitators associated with willingness to use personal health information management (PHIM) systems to support an existing worksite wellness program (WWP). Design . The study design involved a Web-based survey. Setting . The study setting was a regional hospital. Subjects . Hospital employees comprised the study subjects. Measures . Willingness, barriers, and facilitators associated with PHIM were measured. Analysis . Bivariate logit models were used to model two binary dependent variables. One model predicted the likelihood of believing PHIM systems would positively affect overall health and willingness to use. Another predicted the likelihood of worrying about online security and not believing PHIM systems would benefit health goals. Results . Based on 333 responses, believing PHIM systems would positively affect health was highly associated with willingness to use PHIM systems (p < .01). Those comfortable online were 7.22 times more willing to use PHIM systems. Participants in exercise-based components of WWPs were 3.03 times more likely to be willing to use PHIM systems. Those who worried about online security were 5.03 times more likely to believe PHIM systems would not help obtain health goals. Conclusions . Comfort with personal health information online and exercise-based WWP experience was associated with willingness to use PHIM systems. However, nutrition-based WWPs did not have similar effects. Implementation barriers relate to technology anxiety and trust in security, as well as experience with specific WWP activities. Identifying differences between WWP components and addressing technology concerns before implementation of PHIM systems into WWPs may facilitate improved adoption and usage.

  20. Whole-community mutualism: associated invertebrates facilitate a dominant habitat-forming seaweed.

    PubMed

    Bracken, Matthew E S; Gonzalez-Dorantes, Cirse A; Stachowicz, John J

    2007-09-01

    Many habitat-forming, or foundation, species harbor diverse assemblages of associated taxa that benefit from the refuges from predators or harsh physical conditions that foundation species provide. Growing numbers of studies show how specific taxa associated with foundation species can benefit their hosts, but the aggregate effects of the entire community of associated species remain poorly understood. Here, we evaluate the role that a diverse assemblage of invertebrates plays in mediating the dominance of a foundation species, the green filamentous seaweed Cladophora columbiana Collins, in rocky intertidal habitats. Cladophora is a fast-growing seaweed with a high nitrogen demand, and we suggest that it persists in nutrient-limited high-intertidal pools because of local-scale nitrogen excretion by the invertebrate taxa living within its filaments. Removal of associated invertebrates resulted in a fourfold increase in the rate of water-column nitrogen depletion by Cladophora, and ammonium concentrations inside Cladophora turfs with invertebrates present were seven times higher than in the adjacent tide-pool water. The ammonium excreted by invertebrate meiofauna far surpassed the nitrogen used by Cladophora, suggesting that all of Cladophora's nitrogen requirements could be met by the invertebrates associated with it. This study links host performance to the total aggregate biomass of mutualists rather than the particular traits of any one species, suggesting the potential for important feedbacks between individual hosts and the communities of associated species that they support.

  1. Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis

    PubMed Central

    Mishra, Prashant K.; Ciftci-Yilmaz, Sultan; Reynolds, David; Au, Wei-Chun; Boeckmann, Lars; Dittman, Lauren E.; Jowhar, Ziad; Pachpor, Tejaswini; Yeh, Elaine; Baker, Richard E.; Hoyt, M. Andrew; D’Amours, Damien; Bloom, Kerry; Basrai, Munira A.

    2016-01-01

    Sister chromatid cohesion is essential for tension-sensing mechanisms that monitor bipolar attachment of replicated chromatids in metaphase. Cohesion is mediated by the association of cohesins along the length of sister chromatid arms. In contrast, centromeric cohesin generates intrastrand cohesion and sister centromeres, while highly cohesin enriched, are separated by >800 nm at metaphase in yeast. Removal of cohesin is necessary for sister chromatid separation during anaphase, and this is regulated by evolutionarily conserved polo-like kinase (Cdc5 in yeast, Plk1 in humans). Here we address how high levels of cohesins at centromeric chromatin are removed. Cdc5 associates with centromeric chromatin and cohesin-associated regions. Maximum enrichment of Cdc5 in centromeric chromatin occurs during the metaphase-to-anaphase transition and coincides with the removal of chromosome-associated cohesin. Cdc5 interacts with cohesin in vivo, and cohesin is required for association of Cdc5 at centromeric chromatin. Cohesin removal from centromeric chromatin requires Cdc5 but removal at distal chromosomal arm sites does not. Our results define a novel role for Cdc5 in regulating removal of centromeric cohesins and faithful chromosome segregation. PMID:27226485

  2. Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation.

    PubMed

    Sankari, Abdulghani; Bascom, Amy T; Riehani, Anas; Badr, M Safwan

    2015-11-15

    Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 ± 65.0 ms to 750.2 ± 65.0 ms; those with thoracic SCI, from 945.2 ± 65.0 ms to 674.9 ± 65.0 ms; and those who were able-bodied, from 949 ± 75.0 to 682.2 ± 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 ± 0.22 vs. 1.34 ± 0.22 and 0.67 ± 0.23 vs. 1.82 ± 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery.

  3. HIV-associated disruption of mucosal epithelium facilitates paracellular penetration by human papillomavirus.

    PubMed

    Tugizov, Sharof M; Herrera, Rossana; Chin-Hong, Peter; Veluppillai, Piri; Greenspan, Deborah; Michael Berry, J; Pilcher, Christopher D; Shiboski, Caroline H; Jay, Naomi; Rubin, Mary; Chein, Aung; Palefsky, Joel M

    2013-11-01

    The incidence of human papillomavirus (HPV)-associated epithelial lesions is substantially higher in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals. The molecular mechanisms underlying the increased risk of HPV infection in HIV-infected individuals are poorly understood. We found that HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals. Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions (TJ). Treatment of polarized oral, cervical and anal epithelial cells, and oral tissue explants with tat and gp120 led to disruption of epithelial TJ and increased HPV pseudovirion (PsV) paracellular penetration in to the epithelium. PsV entry was observed in the basal/parabasal cells, the cells in which the HPV life cycle is initiated. Our data suggest that HIV-associated TJ disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.

  4. SuhB Associates with Nus Factors To Facilitate 30S Ribosome Biogenesis in Escherichia coli

    PubMed Central

    Singh, Navjot; Bubunenko, Mikhail; Smith, Carol; Abbott, David M.; Stringer, Anne M.; Shi, Ronald; Court, Donald L.

    2016-01-01

    ABSTRACT A complex of highly conserved proteins consisting of NusB, NusE, NusA, and NusG is required for robust expression of rRNA in Escherichia coli. This complex is proposed to prevent Rho-dependent transcription termination by a process known as “antitermination.” The mechanism of this antitermination in rRNA is poorly understood but requires association of NusB and NusE with a specific RNA sequence in rRNA known as BoxA. Here, we identify a novel member of the rRNA antitermination machinery: the inositol monophosphatase SuhB. We show that SuhB associates with elongating RNA polymerase (RNAP) at rRNA in a NusB-dependent manner. Although we show that SuhB is required for BoxA-mediated antitermination in a reporter system, our data indicate that the major function of the NusB/E/A/G/SuhB complex is not to prevent Rho-dependent termination of rRNA but rather to promote correct rRNA maturation. This occurs through formation of a SuhB-mediated loop between NusB/E/BoxA and RNAP/NusA/G. Thus, we have reassigned the function of these proteins at rRNA and identified another key player in this complex. PMID:26980831

  5. Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors

    PubMed Central

    Kothari, P.; De, B. P.; He, B.; Chen, A.; Chiuchiolo, M. J.; Kim, D.; Nikolopoulou, A.; Amor-Coarasa, A.; Dyke, J. P.; Voss, H. U.; Kaminsky, S. M.; Foley, C. P.; Vallabhajosula, S.; Hu, B.; DiMagno, S. G.; Sondhi, D.; Crystal, R. G.; Babich, J. W.; Ballon, D.

    2017-01-01

    Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications. PMID:28059103

  6. DDR complex facilitates global association of RNA polymerase V to promoters and evolutionarily young transposons.

    PubMed

    Zhong, Xuehua; Hale, Christopher J; Law, Julie A; Johnson, Lianna M; Feng, Suhua; Tu, Andy; Jacobsen, Steven E

    2012-09-01

    The plant-specific DNA-dependent RNA polymerase V (Pol V) evolved from Pol II to function in an RNA-directed DNA methylation pathway. Here, we have identified targets of Pol V in Arabidopsis thaliana on a genome-wide scale using ChIP-seq of NRPE1, the largest catalytic subunit of Pol V. We found that Pol V is enriched at promoters and evolutionarily recent transposons. This localization pattern is highly correlated with Pol V-dependent DNA methylation and small RNA accumulation. We also show that genome-wide chromatin association of Pol V is dependent on all members of a putative chromatin-remodeling complex termed DDR. Our study presents a genome-wide view of Pol V occupancy and sheds light on the mechanistic basis of Pol V localization. Furthermore, these findings suggest a role for Pol V and RNA-directed DNA methylation in genome surveillance and in responding to genome evolution.

  7. Drug-facilitated robbery or sexual assault: problems associated with amnesia.

    PubMed

    Goullé, Jean-Pierre; Anger, Jean-Pierre

    2004-04-01

    Amnesia following sedative-hypnotic drug exposure is discussed. Anterograde amnesia clearly occurs with many benzodiazepines. Several drugs are assessed: benzodiazepines and two hypnotics in particular that are structurally unrelated to the benzodiazepines but share some of their properties: zolpidem and zopiclone. The amnesic effects of these drugs are described, memory process, biology of memory, and memory process impairment documented. With these drugs anterograde amnesia has been demonstrated to be dose dependent. This effect is associated with hypnotic drugs, however, the receptors are different. As regards forensic medicine, a significant and specific type of amnesia should be considered: amnesia automatism or amnesic complex automatism. Also, several cases observed in our laboratory are presented to demonstrate the impact of amnesia.

  8. Sleep Improves Prospective Remembering by Facilitating Spontaneous-Associative Retrieval Processes

    PubMed Central

    Diekelmann, Susanne; Wilhelm, Ines; Wagner, Ullrich; Born, Jan

    2013-01-01

    Memories are of the past but for the future, enabling individuals to implement intended plans and actions at the appropriate time. Prospective memory is the specific ability to remember and execute an intended behavior at some designated point in the future. Although sleep is well-known to benefit the consolidation of memories for past events, its role for prospective memory is still not well understood. Here, we show that sleep as compared to wakefulness after prospective memory instruction enhanced the successful execution of prospective memories two days later. We further show that sleep benefited both components of prospective memory, i.e. to remember that something has to be done (prospective component) and to remember what has to be done (retrospective component). Finally, sleep enhanced prospective remembering particularly when attentional resources were reduced during task execution, suggesting that subjects after sleep were able to recruit additional spontaneous-associative retrieval processes to remember intentions successfully. Our findings indicate that sleep supports the maintenance of prospective memory over time by strengthening intentional memory representations, thus favoring the spontaneous retrieval of the intended action at the appropriate time. PMID:24143246

  9. The behavioral and cognitive effects of two benzodiazepines associated with drug-facilitated sexual assault.

    PubMed

    Dowd, Sheila M; Strong, Mary Jane; Janicak, Philip G; Negrusz, Adam

    2002-09-01

    Recently, sexual assaults have included the use of benzodiazepines to impair the victim. Our aim was to examine the physiological, cognitive, and behavioral effects of flunitrazepam (FN) and clonazepam (CLO). In the first study, ten healthy volunteers received a single oral dose of 2 mg of FN. Mini Mental State Examination (MMSE), behavioral reports and staff observations were then collected. In the second study, ten healthy volunteers received a single oral dose of 3 mg of CLO. Vital signs, performance on the MMSE and Digit Symbol Substitution Test, and behavioral changes were examined. FN significantly decreased systolic and diastolic blood pressure 4 h post drug ingestion with diastolic remaining low at 6 h. CLO was associated with changes in temperature and decreased systolic pressure. FN affected memory and attention 4 h following ingestion. CLO affected memory and attention throughout the study (6 h), and psychomotor performance was decreased 2 h post ingestion. In both studies, subjects were disinhibited and did not perceive their own impairment.

  10. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27.

    PubMed

    Bosmann, Markus; Strobl, Birgit; Kichler, Nadia; Rigler, Doris; Grailer, Jamison J; Pache, Florence; Murray, Peter J; Müller, Mathias; Ward, Peter A

    2014-07-01

    The aim of this study was to test the hypothesis that gene expression and release of IL-27 may be modulated by Tyk2. Macrophages derived from the peritoneum or bone marrow of C57BL/10SnJ (WT) mice produced abundant amounts of IL-27(p28) following TLR4 activation by LPS. In contrast, production of IL-27(p28), but not EBI3, was reduced by ∼50% in TLR4-activated macrophages derived from mice with genetic deficiency of Tyk2 compared with WT macrophages. Frequencies of IL-27(p28)+F4/80+CD11b+ cells were lower in TLR4-activated macrophages derived from Tyk2-/- mice. Mechanistically, Tyk2-/- resulted in disruption of a type I IFN-dependent mechanism for production of IL-27(p28), which was induced by type I IFNs, and release of IL-27 was defective in macrophages from IFN-β-/- and IFNAR1-/- mice. In contrast, Tyk2 was not required to mediate the effects of IL-27 on target gene expression in CD4(+) T cells. In vivo, we observed that Tyk2-/- mice have improved survival following endotoxic shock or polymicrobial sepsis induced by CLP. Plasma levels of IL-27(p28) during endotoxic shock or polymicrobial sepsis were markedly reduced in Tyk2-/- mice compared with WT mice. Disruption of IL-27 signaling using IL-27RA-/- mice was protective against sepsis-associated mortality. These data suggest that Tyk2 may mediate adverse outcomes of SIRS by promoting the production of IL-27. In conclusion, this report identifies Tyk2 as a prerequisite factor in the molecular networks that are involved in generation of IL-27.

  11. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    PubMed

    Sufiawati, Irna; Tugizov, Sharof M

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  12. Efficacy of Scutellaria baicalensis for the Treatment of Hand, Foot, and Mouth Disease Associated with Encephalitis in Patients Infected with EV71: A Multicenter, Retrospective Analysis

    PubMed Central

    Lin, Hailong; Zhou, Jian; Lin, Kaichun; Wang, Hongjiao; Liang, Zunhong; Ren, Xingshuai; Huang, Leting

    2016-01-01

    This study aimed to evaluate the clinical efficacy and safety of using the traditional Chinese herbal medicine Scutellaria baicalensis for the treatment of severe HFMD in 725 patients aged >1 year in a multicenter, retrospective analysis. The patients were divided into the S. baicalensis and ribavirin groups, and the temperatures, presence or absence of skin rashes and oral lesions, nervous system (NS) involvement, and viral loads of the patients, as well as the safety of the treatments, were evaluated. The median duration of fever, median time to NS involvement, and the number of patients with oral ulcers and/or vesicles, as well as skin rashes, were decreased in the S. baicalensis group compared with the ribavirin group. In addition, the EV71 viral loads were decreased in the S. baicalensis group, suggesting that S. baicalensis exerted more potent antiviral effects compared with ribavirin. The present study demonstrated that S. baicalensis was suitable for the treatment of severe HFMD in patients aged >1 year, since it was shown to rapidly relieve fever, attenuate oral lesions and rashes, and improve NS involvement. Furthermore, it was demonstrated to be relatively safe for topical application. PMID:27840828

  13. Evaluation of the safety and efficacy of recombinant soluble thrombomodulin for patients with disseminated intravascular coagulation associated with acute leukemia: multicenter prospective study by the Tohoku Hematology Forum.

    PubMed

    Yokoyama, Hisayuki; Takahashi, Naoto; Katsuoka, Yuna; Inomata, Mitsue; Ito, Toshihiro; Meguro, Kuniaki; Kameoka, Yoshihiro; Tsumanuma, Riko; Murai, Kazunori; Noji, Hideyoshi; Ishizawa, Kenichi; Ito, Shigeki; Onishi, Yasushi; Harigae, Hideo

    2017-02-07

    It has been suggested that use of recombinant soluble thrombomodulin (rTM) is superior to conventional drugs in treatment of disseminated intravascular coagulation (DIC) complicating acute leukemia. However, its safety and efficacy have not been fully examined in prospective studies. Here, we performed a multicenter prospective study to examine outcomes of rTM treatment for DIC in patients with acute leukemia. Of 33 patients registered in this study, 13 had acute myeloid leukemia (AML), three had acute lymphoblastic leukemia (ALL), and 17 had acute promyelocytic leukemia (APL). The cumulative rates of DIC resolution at day 7 and day 35 were 56 and 81% in AML/ALL and 53 and 77% in APL, respectively. The median time from the initiation of rTM to DIC resolution was 4 days in AML/ALL and 6 days in APL patients. Adverse events related to hemorrhage occurred in two AML/ALL patients (13%) and three APL patients (18%). Of these, one AML/ALL patient died with intracranial hemorrhage, and two APL patients died with intracranial hemorrhage and pulmonary hemorrhage. These results suggest that rTM may improve the survival of acute leukemia patients with DIC by inhibiting early death related to hemorrhagic events, as reported previously.

  14. Kinematic and kinetic improvements associated with action observation facilitated learning of the power clean in Australian footballers.

    PubMed

    Sakadjian, Alex; Panchuk, Derek; Pearce, Alan J

    2014-06-01

    This study investigated the effectiveness of action observation (AO) on facilitating learning of the power clean technique (kinematics) compared with traditional strength coaching methods and whether improvements in performance (kinetics) were associated with an improvement in lifting technique. Fifteen subjects (age, 20.9 ± 2.3 years) with no experience in performing the power clean exercise attended 12 training and testing sessions over a 4-week period. Subjects were assigned to 2 matched groups, based on preintervention power clean performance and performed 3 sets of 5 repetitions of the power clean exercise at each training session. Subjects in the traditional coaching group (TC; n = 7) received the standard coaching feedback (verbal cues and physical practice), whereas subjects in the AO group (n = 8) received similar verbal coaching cues and physical practice but also observed a video of a skilled model before performing each set. Kinematic data were collected from video recordings of subjects who were fitted with joint center markings during testing, whereas kinetic data were collected from a weightlifting analyzer attached to the barbell. Subjects were tested before intervention, at the end of weeks 2 and 3, and at after intervention at the end of week 4. Faster improvements (3%) were observed in power clean technique with AO-facilitated learning in the first week and performance improvements (mean peak power of the subject's 15 repetitions) over time were significant (p < 0.001). In addition, performance improvement was significantly associated (R = 0.215) with technique improvements. In conclusion, AO combined with verbal coaching and physical practice of the power clean exercise resulted in significantly faster technique improvements and improvement in performance compared with traditional coaching methods.

  15. The Lhs1/GRP170 Chaperones Facilitate the Endoplasmic Reticulum-associated Degradation of the Epithelial Sodium Channel*

    PubMed Central

    Buck, Teresa M.; Plavchak, Lindsay; Roy, Ankita; Donnelly, Bridget F.; Kashlan, Ossama B.; Kleyman, Thomas R.; Subramanya, Arohan R.; Brodsky, Jeffrey L.

    2013-01-01

    The epithelial sodium channel, ENaC, plays a critical role in maintaining salt and water homeostasis, and not surprisingly defects in ENaC function are associated with disease. Like many other membrane-spanning proteins, this trimeric protein complex folds and assembles inefficiently in the endoplasmic reticulum (ER), which results in a substantial percentage of the channel being targeted for ER-associated degradation (ERAD). Because the spectrum of factors that facilitates the degradation of ENaC is incomplete, we developed yeast expression systems for each ENaC subunit. We discovered that a conserved Hsp70-like chaperone, Lhs1, is required for maximal turnover of the ENaC α subunit. By expressing Lhs1 ATP binding mutants, we also found that the nucleotide exchange properties of this chaperone are dispensable for ENaC degradation. Consistent with the precipitation of an Lhs1-αENaC complex, Lhs1 holdase activity was instead most likely required to support the ERAD of αENaC. Moreover, a complex containing the mammalian Lhs1 homolog GRP170 and αENaC co-precipitated, and GRP170 also facilitated ENaC degradation in human, HEK293 cells, and in a Xenopus oocyte expression system. In both yeast and higher cell types, the effect of Lhs1 on the ERAD of αENaC was selective for the unglycosylated form of the protein. These data establish the first evidence that Lhs1/Grp170 chaperones can act as mediators of ERAD substrate selection. PMID:23645669

  16. The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study

    PubMed Central

    Davis, Allan P; Murphy, Cynthia G; Rosenstein, Michael C; Wiegers, Thomas C; Mattingly, Carolyn J

    2008-01-01

    integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug. PMID:18845002

  17. Assessing tobacco use by cancer patients and facilitating cessation: an American Association for Cancer Research policy statement.

    PubMed

    Toll, Benjamin A; Brandon, Thomas H; Gritz, Ellen R; Warren, Graham W; Herbst, Roy S

    2013-04-15

    When diagnosed with cancer, patients can immediately make a meaningful positive impact on their health by stopping their tobacco use. Scientific evidence clearly shows that tobacco use in patients with cancer leads to poorer outcomes. The specific biological processes driving tobacco consumption's interference in cancer therapy are the subject of continuing research, but the evidence is clear that tobacco use in patients with cancer leads to decreased treatment efficacy and safety, decreased survival, decreased quality of life, increased treatment-related toxicity, and increased risk of cancer recurrence and second primary tumors. Data suggest that tobacco cessation can improve outcomes and survival in patients with cancer, yet full execution of evidence-based cessation interventions is infrequent in oncology settings. Therefore, both improved provision of cessation assistance to all patients with cancer who use tobacco or have recently quit and further study of the deleterious effects of tobacco use and benefits of tobacco cessation on cancer progression and treatment are needed and recommended by the American Association for Cancer Research. Progress on both fronts begins with universal assessment and documentation of tobacco use as a standard of quality cancer care regardless of treatment setting and will be further facilitated through the development of reliable, valid, and standard measures of tobacco use, incorporation of evidence-based procedures into quality and accreditation procedures, and the development of appropriate training, clinical infrastructure, and incentives for delivery of tobacco cessation interventions.

  18. Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus.

    PubMed

    Wang, S; Olumolade, O O; Sun, T; Samiotaki, G; Konofagou, E E

    2015-01-01

    Recombinant adeno-associated virus (rAAV) has shown great promise as a potential cure for neurodegenerative diseases. The existence of the blood-brain barrier (BBB), however, hinders efficient delivery of the viral vectors. Direct infusion through craniotomy is the most commonly used approach to achieve rAAV delivery, which carries increased risks of infection and other complications. Here, we report a focused ultrasound (FUS)-facilitated noninvasive rAAV delivery paradigm that is capable of producing targeted and neuron-specific transductions. Oscillating ultrasound contrast agents (microbubbles), driven by FUS waves, temporarily 'unlock' the BBB, allowing the systemically administrated rAAVs to enter the brain parenchyma, while maintaining their bioactivity and selectivity. Taking the advantage of the neuron-specific promoter synapsin, rAAV gene expression was triggered almost exclusively (95%) in neurons of the targeted caudate-putamen region. Both behavioral assessment and histological examination revealed no significant long-term adverse effects (in the brain and several other critical organs) for this combined treatment paradigm. Results from this study demonstrated the feasibility and safety for the noninvasive, targeted rAAV delivery, which might have open a new avenue in gene therapy in both preclinical and clinical settings.

  19. S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells.

    PubMed

    Barry, Sayka; Chelala, Claude; Lines, Kate; Sunamura, Makoto; Wang, Amu; Marelli-Berg, Federica M; Brennan, Caroline; Lemoine, Nicholas R; Crnogorac-Jurcevic, Tatjana

    2013-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the 5th most common cause of cancer death in the UK and the 4th in the US. The vast majority of deaths following pancreatic cancer are due to metastatic spread, hence understanding the metastatic process is vital for identification of critically needed novel therapeutic targets. An enriched set of 33 genes differentially expressed in common between primary PDAC and liver metastases, when compared to normal tissues, was obtained through global gene expression profiling. This metastasis-associated gene set comprises transcripts from both cancer (S100P, S100A6, AGR2, etc.) and adjacent stroma (collagens type I, III, and V, etc.), thus reinforcing the concept of a continuous crosstalk between the two compartments in both primary tumours and their metastases. The expression of S100P, SFN, VCAN and collagens was further validated in additional primary PDACs and matched liver metastatic lesions, while the functional significance of one of the most highly expressed genes, S100P, was studied in more detail. We show that this protein increases the transendothelial migration of PDAC cancer cells in vitro, which was also confirmed in vivo experiments using a zebrafish embryo model. Thus S100P facilitates cancer cell intravasation/extravasation, critical steps in the hematogenous dissemination of pancreatic cancer cells.

  20. Transmembrane TNF-α Facilitates HIV-1 Infection of Podocytes Cultured from Children with HIV-Associated Nephropathy.

    PubMed

    Li, Jinliang; Das, Jharna R; Tang, Pingtao; Han, Zhe; Jaiswal, Jyoti K; Ray, Patricio E

    2017-03-01

    Studies have shown that podocytes and renal tubular epithelial cells from patients with HIV-associated nephropathy (HIVAN) express HIV-1 transcripts, suggesting that productive infection of renal epithelial cells precipitates development of HIVAN. However, podocytes and renal tubular epithelial cells do not express CD4 receptors, and it is unclear how these cells become productively infected in vivo We investigated the mechanisms underlying the infection by HIV-1 of podocytes cultured from the urine of children with HIVAN. We observed low-level productive infection on exposure of these cells to primary cell-free HIV-1 supernatants. However, envelope-defective recombinant HIV-1 did not infect the renal epithelial cell lines. Moreover, treatment of podocytes to inhibit endocytic transport or dynamin activity or remove cell surface heparan sulfate proteoglycans reduced infection efficiency. Transfection of CD4- 293T cells with a cDNA expression library developed from a podocyte cell line derived from a child with HIVAN led to the identification of TNF-α as a possible mediator of HIV-1 infection. Overexpression of transmembrane TNF-α in cultured CD4- renal tubular epithelial cells, 293T cells, and HeLa cells enabled the infection of these cells; exposure to soluble TNF-α did not. Immunohistochemistry showed TNF-α expression in podocytes of renal sections from children with HIVAN. Furthermore, we found that TNF-α enhanced NF-κB activation and integration of HIV-1 into the podocyte DNA. Finally, inhibition of dynamin activity blocked TNF-α-mediated infection. These data establish a role for transmembrane TNF-α in facilitating the viral entry and integration of HIV-1 into the DNA of renal epithelial cells.

  1. Association between barriers and facilitators to meeting the Dietary Guidelines for Americans and body weight status of caregiver-child dyads: The HEALTH study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Few Americans meet the Dietary Guidelines for Americans (DGA) yet, a large percentage are overweight. The goal of this research was to examine the association between barriers and facilitators to meeting the DGA and weight in a multi-site study. In a cross-sectional study, a total of 836 caregiver-c...

  2. NPR-C gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: a multicenter study

    PubMed Central

    Hu, Qin; Liu, Qiji; Wang, Shasha; Zhen, Xi; Zhang, Zhimian; Lv, Ruijuan; Jiang, Guihua; Ma, Zhiyong; He, Hong; Li, Daqing; Liu, Xiaoling; Gao, Fei; Li, Jifu; Li, Li; Zhang, Mei; Ji, Xiaoping; Chen, Yuguo; Wang, Daowen; Huang, Dejia; Ma, Aiqun; Huang, Wei; Zhao, Yuxia; Gong, Yaoqin; Zhang, Cheng; Zhang, Yun

    2016-01-01

    To find a new locus that confers significant susceptibility to CAD in Chinese Han population, a genome-wide association study in 200 “extreme individuals” from a Shandong cohort and a pathway-based candidate gene study from a Shanghai cohort (293 CAD/293 controls) were simultaneously performed. Amongst them, 13 SNPs associated with CAD were selected to conduct validation and replication studies in additional 3363 CAD patients and 3148 controls. A novel locus rs700926 in natriuretic peptide receptor C (NPR-C) was identified in Shandong and Hubei cohorts. Then rs700926 and other nine tag SNPs were genotyped in four geographically different populations (Shandong, Shaanxi, Hubei and Sichuan cohorts), and 6 SNPs (rs700926, rs1833529, rs2270915, rs17541471, rs3792758 and rs696831) showed stronger association with CAD, regardless of single or combined analysis. We further genotyped rs2270915 and 10 additional tag SNPs in a central China cohort and identified rs12697273 and rs10066436 as the loci associated with CAD. All these positive associations remained significant after adjustment for traditional risk factors of CAD. NPR-C gene SNPs significantly contribute to CAD susceptibility in the Chinese Han population. PMID:27191271

  3. A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus

    PubMed Central

    Alter, Harvey J.; Mikovits, Judy A.; Switzer, William M.; Ruscetti, Francis W.; Lo, Shyh-Ching; Klimas, Nancy; Komaroff, Anthony L.; Montoya, Jose G.; Bateman, Lucinda; Levine, Susan; Peterson, Daniel; Levin, Bruce; Hanson, Maureen R.; Genfi, Afia; Bhat, Meera; Zheng, HaoQiang; Wang, Richard; Li, Bingjie; Hung, Guo-Chiuan; Lee, Li Ling; Sameroff, Stephen; Heneine, Walid; Coffin, John; Hornig, Mady; Lipkin, W. Ian

    2012-01-01

    ABSTRACT The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. PMID:22991430

  4. EEG Abnormalities Are Associated With Poorer Depressive Symptom Outcomes With Escitalopram and Venlafaxine-XR, but Not Sertraline: Results From the Multicenter Randomized iSPOT-D Study.

    PubMed

    Arns, Martijn; Gordon, Evian; Boutros, Nash N

    2017-01-01

    Rationale Limited research is available on electrophysiological abnormalities such as epileptiform EEG or EEG slowing in depression and its association with antidepressant treatment response. Objectives We investigated the association between EEG abnormalities and antidepressant treatment response in the international Study to Predict Optimized Treatment in Depression (iSPOT-D). Methods Of 1008 participants with major depressive disorder randomized to escitalopram, sertraline, or venlafaxine-XR, 622 completed 8 weeks of treatment per protocol. The study also recruited 336 healthy controls. Treatment response was established after 8 weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed. EEG abnormalities including epileptiform activity, EEG slowing, and alpha peak frequency (APF) were scored for all subjects, blind to treatment outcome. Results Patients and controls did not differ in the occurrence of EEG abnormalities. Furthermore, in the per protocol sample the occurrence of epileptiform EEG and EEG slowing (as a combined marker) were associated with a reduced likelihood of responding to escitalopram (P = .019; odds ratio [OR] = 3.56) and venlafaxine-XR (P = .043; OR = 2.76), but not sertraline (OR = 0.73). The response rates for this "any EEG abnormality" groups versus the "no-abnormality" group were 33% and 64% for escitalopram and 41% and 66% for venlafaxine-XR, respectively. A slow APF was associated with treatment response only in the sertraline group (P = .21; d = .027). Conclusions EEG abnormalities are associated with nonresponse to escitalopram and venlafaxine-XR, but not sertraline, whereas a slow APF is associated to response for sertraline only.

  5. Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

    PubMed Central

    Omore, Richard; Tate, Jacqueline E.; O’Reilly, Ciara E.; Ayers, Tracy; Williamson, John; Moke, Feny; Schilling, Katie A.; Awuor, Alex O.; Jaron, Peter; Ochieng, John B.; Oundo, Joseph; Parashar, Umesh D.; Parsons, Michele B.; Bopp, Cheryl C.; Nasrin, Dilruba; Farag, Tamer H.; Kotloff, Karen L.; Nataro, James P.; Panchalingam, Sandra; Levine, Myron M.; Laserson, Kayla F.; Nuorti, J. Pekka; Mintz, Eric D.; Breiman, Robert F.

    2016-01-01

    Objective To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. Methods We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. Results From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0–11 months old (aOR = 5.29, 95% CI 3.14–8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91–3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Conclusions Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. PMID:27494517

  6. Defining Competencies for Associate Degree Nursing Education and Practice. Proceedings of the Midwest Regional Conference on "The Associate Degree Nursing--Facilitating Competency Development" Project (Chicago, Illinois, March 10-11, 1983).

    ERIC Educational Resources Information Center

    Minckley, Barbara B., Ed.; Walters, Mary Dale, Ed.

    Focusing on "Associate Degree Nursing--Facilitating Competency Development," a 3-year project sponsored by the Midwest Alliance in Nursing (MAIN) to explore and recommend ways of strengthening Associate Degree Nursing (ADN) education and service, these proceedings contain papers by individuals involved with the development of the project and those…

  7. Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study.

    PubMed

    Requena, Pilar; Arévalo-Herrera, Myriam; Menegon, Michela; Martínez-Espinosa, Flor E; Padilla, Norma; Bôtto-Menezes, Camila; Malheiro, Adriana; Hans, Dhiraj; Castellanos, Maria Eugenia; Robinson, Leanne; Samol, Paula; Kochar, Swati; Kochar, Sanjay K; Kochar, Dhanpat K; Desai, Meghna; Sanz, Sergi; Quintó, Llorenç; Mayor, Alfredo; Rogerson, Stephen; Mueller, Ivo; Severini, Carlo; Del Portillo, Hernando A; Bardají, Azucena; Chitnis, Chetan C; Menéndez, Clara; Dobaño, Carlota

    2017-01-01

    A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman's rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood mononuclear

  8. Naturally Acquired Binding-Inhibitory Antibodies to Plasmodium vivax Duffy Binding Protein in Pregnant Women Are Associated with Higher Birth Weight in a Multicenter Study

    PubMed Central

    Requena, Pilar; Arévalo-Herrera, Myriam; Menegon, Michela; Martínez-Espinosa, Flor E.; Padilla, Norma; Bôtto-Menezes, Camila; Malheiro, Adriana; Hans, Dhiraj; Castellanos, Maria Eugenia; Robinson, Leanne; Samol, Paula; Kochar, Swati; Kochar, Sanjay K.; Kochar, Dhanpat K.; Desai, Meghna; Sanz, Sergi; Quintó, Llorenç; Mayor, Alfredo; Rogerson, Stephen; Mueller, Ivo; Severini, Carlo; del Portillo, Hernando A.; Bardají, Azucena; Chitnis, Chetan C.; Menéndez, Clara; Dobaño, Carlota

    2017-01-01

    A vaccine to eliminate malaria would need a multi-stage and multi-species composition to achieve robust protection, but the lack of knowledge about antigen targets and mechanisms of protection precludes the development of fully efficacious malaria vaccines, especially for Plasmodium vivax (Pv). Pregnant women constitute a risk population who would greatly benefit from a vaccine preventing the adverse events of Plasmodium infection during gestation. We hypothesized that functional immune responses against putative targets of naturally acquired immunity to malaria and vaccine candidates will be associated with protection against malaria infection and/or poor outcomes during pregnancy. We measured (i) IgG responses to a large panel of Pv and Plasmodium falciparum (Pf) antigens, (ii) the capacity of anti-Pv ligand Duffy binding protein (PvDBP) antibodies to inhibit binding to Duffy antigen, and (iii) cellular immune responses to two Pv antigens, in a subset of 1,056 pregnant women from Brazil, Colombia, Guatemala, India, and Papua New Guinea (PNG). There were significant intraspecies and interspecies correlations for most antibody responses (e.g., PfMSP119 versus PfAMA1, Spearman’s rho = 0.81). Women from PNG and Colombia had the highest levels of IgG overall. Submicroscopic infections seemed sufficient to boost antibody responses in Guatemala but not antigen-specific cellular responses in PNG. Brazil had the highest percentage of Duffy binding inhibition (p-values versus Colombia: 0.040; Guatemala: 0.047; India: 0.003, and PNG: 0.153) despite having low anti-PvDBP IgG levels. Almost all antibodies had a positive association with present infection, and coinfection with the other species increased this association. Anti-PvDBP, anti-PfMSP1, and anti-PfAMA1 IgG levels at recruitment were positively associated with infection at delivery (p-values: 0.010, 0.003, and 0.023, respectively), suggesting that they are markers of malaria exposure. Peripheral blood

  9. Association of SULT1A1 Arg²¹³His polymorphism with male breast cancer risk: results from a multicenter study in Italy.

    PubMed

    Ottini, L; Rizzolo, P; Zanna, I; Silvestri, V; Saieva, C; Falchetti, M; Masala, G; Navazio, A S; Capalbo, C; Bianchi, S; Manoukian, S; Barile, M; Peterlongo, P; Caligo, M A; Varesco, L; Tommasi, S; Russo, A; Giannini, G; Cortesi, L; Cini, G; Montagna, M; Radice, P; Palli, D

    2014-12-01

    Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical-pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical-pathologic features. A significant difference in the distribution of SULT1A1 Arg(213)His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.

  10. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

    PubMed Central

    Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

    2014-01-01

    Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose

  11. A multicenter study to quantify systematic variations and associated uncertainties in source positioning with commonly used HDR afterloaders and ring applicators for the treatment of cervical carcinomas

    SciTech Connect

    Awunor, O.; Berger, D.; Kirisits, C.

    2015-08-15

    Purpose: The reconstruction of radiation source position in the treatment planning system is a key part of the applicator reconstruction process in high dose rate (HDR) brachytherapy treatment of cervical carcinomas. The steep dose gradients, of as much as 12%/mm, associated with typical cervix treatments emphasize the importance of accurate and precise determination of source positions. However, a variety of methodologies with a range in associated measurement uncertainties, of up to ±2.5 mm, are currently employed by various centers to do this. In addition, a recent pilot study by Awunor et al. [“Direct reconstruction and associated uncertainties of {sup 192}Ir source dwell positions in ring applicators using gafchromic film in the treatment planning of HDR brachytherapy cervix patients,” Phys. Med. Biol. 58, 3207–3225 (2013)] reported source positional differences of up to 2.6 mm between ring sets of the same type and geometry. This suggests a need for a comprehensive study to assess and quantify systematic source position variations between commonly used ring applicators and HDR afterloaders across multiple centers. Methods: Eighty-six rings from 20 European brachytherapy centers were audited in the form of a postal audit with each center collecting the data independently. The data were collected by setting up the rings using a bespoke jig and irradiating gafchromic films at predetermined dwell positions using four afterloader types, MicroSelectron, Flexitron, GammaMed, and MultiSource, from three manufacturers, Nucletron, Varian, and Eckert & Ziegler BEBIG. Five different ring types in six sizes (Ø25–Ø35 mm) and two angles (45° and 60°) were used. Coordinates of irradiated positions relative to the ring center were determined and collated, and source position differences quantified by ring type, size, and angle. Results: The mean expanded measurement uncertainty (k = 2) along the direction of source travel was ±1.4 mm. The standard deviation

  12. Associations among Visual Acuity and Vision- and Health-Related Quality of Life among Patients in the Multicenter Uveitis Steroid Treatment Trial

    PubMed Central

    Drye, Lea T.; Kempen, John H.; Dunn, James P.; Holland, Gary N.; Latkany, Paul; Rao, Narsing A.; Sen, H. Nida; Sugar, Elizabeth A.; Thorne, Jennifer E.; Wang, Robert C.; Holbrook, Janet T.

    2012-01-01

    Purpose. To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis. Methods. Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL. Results. Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29–0.52). Conclusions. The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost–utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.) PMID:22247489

  13. Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

    PubMed Central

    Shen, Guo-Shuang; Zhao, Jiu-Da; Zhao, Jun-Hui; Ma, Xin-Fu; Du, Feng; Kan, Jie; Ji, Fa-Xiang; Ma, Fei; Zheng, Fang-Chao; Wang, Zi-Yi; Xu, Bing-He

    2016-01-01

    AIM: To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection. METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors. RESULTS: Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P < 0.001), tumor location (P = 0.001), pathological grade (P < 0.001), TNM stage (P < 0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population. PMID:27340357

  14. Acquired BRAF inhibitor resistance: a multicenter meta-analysis of the spectrum and frequencies, clinical behavior, and phenotypic associations of resistance mechanisms

    PubMed Central

    Johnson, Douglas B.; Menzies, Alexander M.; Zimmer, Lisa; Eroglu, Zeynep; Ye, Fei; Zhao, Shilin; Rizos, Helen; Sucker, Antje; Scolyer, Richard A.; Gutzmer, Ralf; Gogas, Helen; Kefford, Richard F.; Thompson, John F.; Becker, Jürgen C.; Berking, Carola; Egberts, Friederike; Loquai, Carmen; Goldinger, Simone M.; Pupo, Gulietta M.; Hugo, Willy; Kong, Xiangju; Garraway, Levi A.; Sosman, Jeffrey A.; Ribas, Antoni; Lo, Roger S.; Long, Georgina V.; Schadendorf, Dirk

    2015-01-01

    Background Acquired resistance to BRAF inhibitors (BRAFi) is a near-universal phenomenon caused by numerous genetic and non-genetic alterations. In this study, we evaluated the spectrum, onset, pattern of progression, and subsequent clinical outcomes associated with specific mechanisms of resistance. Methods We compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole exome sequencing and/or PCR-based genetic testing. Results Among 132 samples, putative resistance mechanisms were identified in 58%, including NRAS or KRAS mutations (20%), BRAF splice variants (16%), BRAFV600E/K amplifications (13%), MEK1/2 mutations (7%), and non-MAPK pathway alterations (11%). Marked heterogeneity was observed within tumors and patients; 18 of 19 patients (95%) with >1 progression biopsy had distinct/unknown drivers of resistance between samples. NRAS mutations were associated with vemurafenib use (p=0.045) and intracranial metastases (p=0.036), and MEK1/2 mutations correlated with hepatic progression (p=0.011). Progression-free survival and overall survival were similar across resistance mechanisms. The median survival after disease progression was 6.9 months, and responses to subsequent BRAF and MEK inhibition were uncommon (2 of 15; 13%). Post-progression outcomes did not correlate with specific acquired BRAFi resistance mechanisms. Conclusions This is the first study to systematically characterize the clinical implications of particular acquired BRAFi resistance mechanisms in patients with BRAF-mutant melanoma largest study to compile the landscape of resistance. Despite marked heterogeneity of resistance mechanisms within patients, NRAS mutations correlated with vemurafenib use and intracranial disease involvement. PMID:26608120

  15. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study

    PubMed Central

    2016-01-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout. PMID:27550484

  16. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    PubMed

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout.

  17. Clinical and epidemiological factors associated with methicillin resistance in community-onset invasive Staphylococcus aureus infections: prospective multicenter cross-sectional study in Korea.

    PubMed

    Kim, Eu Suk; Kim, Hong Bin; Kim, Gayeon; Kim, Kye-Hyung; Park, Kyung-Hwa; Lee, Shinwon; Choi, Young Hwa; Yi, Jongyoun; Kim, Chung Jong; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Kim, Nam-Joong; Lee, Yeong-Seon; Oh, Myoung-Don

    2014-01-01

    Successful empirical therapy of Staphylococcus aureus infections requires the ability to predict methicillin resistance. Our aim was to identify predictors of methicillin resistance in community-onset (CO) invasive S. aureus infections. Sixteen hospitals across Korea participated in this study from May to December 2012. We prospectively included cases of S. aureus infection in which S. aureus was isolated from sterile clinical specimens ≤ 72 hours after hospitalization. Clinical and epidemiological data were gathered and compared in methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) cases. Community-associated (CA) infections were defined as in previous studies. In total, there were 786 cases of community-onset S. aureus infection, 102 (13.0%) of which were CA-MRSA. In addition to known risk factors, exposure to 3rd generation cephalosporins in the past 6 months [odds ratio (OR), 1.922; 95% confidence interval (CI), 1.176-3.142] and close contact with chronically ill patients in the past month (OR, 2.647; 95% CI, 1.189-5.891) were independent risk factors for MRSA infection. However, no clinical predictors of CA-MRSA were identified. Methicillin resistance, CO infection, and appropriateness of empirical antibiotics were not significantly related to 30-day mortality. MRSA infection should be suspected in patients recently exposed to 3rd generation cephalosporins or chronically-ill patients. There were no reliable predictors of CA-MRSA infection, and mortality was not affected by methicillin resistance.

  18. Protein tyrosine phosphatases PTP-1B, SHP-2, and PTEN facilitate Rb/E2F-associated apoptotic signaling.

    PubMed

    Morales, Liza D; Casillas Pavón, Edgar A; Shin, Jun Wan; Garcia, Alexander; Capetillo, Mario; Kim, Dae Joon; Lieman, Jonathan H

    2014-01-01

    To maintain tissue homeostasis, apoptosis is functionally linked to the cell cycle through the retinoblastoma (Rb)/E2F pathway. When the Rb tumor suppressor protein is functionally inactivated, E2F1 elicits an apoptotic response through both intrinsic (caspase-9 mediated) and extrinsic (caspase-8 mediated) apoptotic pathways in order to eliminate hyperproliferative cells. Rb/E2F-associated apoptosis has been demonstrated to be associated with the loss of constitutive transcriptional repression by Rb/E2F complexes and mediated by caspase-8. Protein tyrosine phosphatases (PTPs) PTP-1B and SHP-2 have been previously shown to be directly activated by loss of Rb/E2F repression during Rb/E2F-associated apoptosis. In this current study, we demonstrate that the PTEN tumor suppressor is also directly activated by loss of Rb/E2F repression. We also demonstrate that PTP-1B, SHP-2, and PTEN play a functional role in Rb/E2F-associated apoptosis. Knockdown of PTP1B, SHP2, or PTEN expression with small interfering RNA (siRNA) in apoptotic cells increases cell viability and rescues cells from the Rb/E2F-associated apoptotic response. Furthermore, rescue from apoptosis coincides with inhibition of caspase-8 and caspase-3 cleavage (activation). Our results indicate PTP-1B, SHP-2, and PTEN all play a functional role in Rb/E2F-associated apoptotic signal transduction and provide further evidence that PTP-1B, SHP-2, and PTEN can contribute to tumor suppression through an Rb/E2F-associated mechanism.

  19. "We as Black Men Have to Encourage Each other:" Facilitators and Barriers Associated with HIV Testing among Black/African American Men in Rural Florida.

    PubMed

    Murray, Ashley; Toledo, Lauren; Brown, Emma Ej; Sutton, Madeline Y

    2017-01-01

    HIV testing for some African American men remains a challenge, and effective interventions are lacking. We explored facilitators and barriers associated with HIV testing among heterosexual African American men in rural Florida. We conducted focus group interviews with 67 African American men who were low-income, and HIV-uninfected based on prior testing or had unknown HIV status. Using computer-assisted thematic analyses, we examined transcribed focus group responses for main themes. Thematic analyses revealed three main themes regarding facilitators of HIV testing: 1) using preferred HIV testing community locations (park, library, gym); 2) receiving incentives (food or money); and 3) the importance of peer-led messaging for free, rapid HIV testing. Barriers included HIV testing at the local health department, and perceived social and emotional consequences to testing and the possibility of receiving a positive result. Effective HIV testing interventions for heterosexual African American men in rural Florida may need to incorporate suggested facilitators and reduce perceived barriers in order to improve HIV testing strategies.

  20. It Takes Two to Tango: In Dynamic Inquiry, the Self-Directed Student Acts in Association with the Facilitating Teacher

    ERIC Educational Resources Information Center

    Zion, M.; Slezak, M.

    2005-01-01

    The current research presents a qualitative view of a teacher-student association within the context of dynamic inquiry, as encouraged by a new biology curriculum, ''Biomind''. This curriculum enables open inquiry learning through teacher guidance. We characterized the various aspects of the student's functioning as a self-directed student during…

  1. New database facilitates characterization of flavonoid intake, sources, and positive associations with diet quality among U.S. adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiologic studies show inverse associations between flavonoid intake and chronic disease risk. However, a lack of comprehensive databases of the flavonoid content of foods has hindered efforts to fully characterize population intake. Using a newly released database of flavonoid values, we soug...

  2. A New Database Facilitates Characterization of Flavonoid Intake, Sources, and Positive Associations with Diet Quality among US Adults12

    PubMed Central

    Wilkinson Enns, Cecilia; Goldman, Joseph D; Martin, Carrie L; Steinfeldt, Lois C; Murayi, Theophile; Moshfegh, Alanna J

    2015-01-01

    Background: Epidemiologic studies demonstrate inverse associations between flavonoid intake and chronic disease risk. However, lack of comprehensive databases of the flavonoid content of foods has hindered efforts to fully characterize population intakes and determine associations with diet quality. Objectives: Using a newly released database of flavonoid values, this study sought to describe intake and sources of total flavonoids and 6 flavonoid classes and identify associations between flavonoid intake and the Healthy Eating Index (HEI) 2010. Methods: One day of 24-h dietary recall data from adults aged ≥20 y (n = 5420) collected in What We Eat in America (WWEIA), NHANES 2007–2008, were analyzed. Flavonoid intakes were calculated using the USDA Flavonoid Values for Survey Foods and Beverages 2007–2008. Regression analyses were conducted to provide adjusted estimates of flavonoid intake, and linear trends in total and component HEI scores by flavonoid intake were assessed using orthogonal polynomial contrasts. All analyses were weighted to be nationally representative. Results: Mean intake of flavonoids was 251 mg/d, with flavan-3-ols accounting for 81% of intake. Non-Hispanic whites had significantly higher (P < 0.001) intakes of total flavonoids (275 mg/d) than non-Hispanic blacks (176 mg/d) and Hispanics (139 mg/d). Tea was the primary source (80%) of flavonoid intake. Regardless of whether the flavonoid contribution of tea was included, total HEI score and component scores for total fruit, whole fruit, total vegetables, greens and beans, seafood and plant proteins, refined grains, and empty calories increased (P < 0.001) across flavonoid intake quartiles. Conclusions: A new database that permits comprehensive estimation of flavonoid intakes in WWEIA, NHANES 2007–2008; identification of their major food/beverage sources; and determination of associations with dietary quality will lead to advances in research on relations between flavonoid intake and

  3. Increased power of mixed models facilitates association mapping of 10 loci for metabolic traits in an isolated population.

    PubMed

    Kenny, Eimear E; Kim, Minseung; Gusev, Alexander; Lowe, Jennifer K; Salit, Jacqueline; Smith, J Gustav; Kovvali, Sirisha; Kang, Hyun Min; Newton-Cheh, Christopher; Daly, Mark J; Stoffel, Markus; Altshuler, David M; Friedman, Jeffrey M; Eskin, Eleazar; Breslow, Jan L; Pe'er, Itsik

    2011-02-15

    The potential benefits of using population isolates in genetic mapping, such as reduced genetic, phenotypic and environmental heterogeneity, are offset by the challenges posed by the large amounts of direct and cryptic relatedness in these populations confounding basic assumptions of independence. We have evaluated four representative specialized methods for association testing in the presence of relatedness; (i) within-family (ii) within- and between-family and (iii) mixed-models methods, using simulated traits for 2906 subjects with known genome-wide genotype data from an extremely isolated population, the Island of Kosrae, Federated States of Micronesia. We report that mixed models optimally extract association information from such samples, demonstrating 88% power to rank the true variant as among the top 10 genome-wide with 56% achieving genome-wide significance, a >80% improvement over the other methods, and demonstrate that population isolates have similar power to non-isolate populations for observing variants of known effects. We then used the mixed-model method to reanalyze data for 17 published phenotypes relating to metabolic traits and electrocardiographic measures, along with another 8 previously unreported. We replicate nine genome-wide significant associations with known loci of plasma cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, thyroid stimulating hormone, homocysteine, C-reactive protein and uric acid, with only one detected in the previous analysis of the same traits. Further, we leveraged shared identity-by-descent genetic segments in the region of the uric acid locus to fine-map the signal, refining the known locus by a factor of 4. Finally, we report a novel associations for height (rs17629022, P< 2.1 × 10⁻⁸).

  4. Membrane-associated aquaporin-1 facilitates osmotically driven water flux across the basolateral membrane of the thick ascending limb

    PubMed Central

    Cabral, Pablo D.

    2012-01-01

    The thick ascending limb of the loop of Henle (TAL) reabsorbs ∼30% of filtered NaCl but is impermeable to water. The observation that little water traverses the TAL indicates an absence of water channels at the apical membrane. Yet TAL cells swell when peritubular osmolality decreases indicating that water channels must be present in the basolateral side. Consequently, we hypothesized that the water channel aquaporin-1 (AQP1) facilitates water flux across the basolateral membrane of TALs. Western blotting revealed AQP1 expression in microdissected rat and mouse TALs. Double immunofluorescence showed that 95 ± 2% of tubules positive for the TAL-specific marker Tamm-Horsfall protein were also positive for AQP1 (n = 6). RT-PCR was used to demonstrate presence of AQP1 mRNA and the TAL-specific marker NKCC2 in microdissected TALs. Cell surface biotinylation assays showed that 23 ± 3% of the total pool of AQP1 was present at the TAL basolateral membrane (n = 7). To assess the functional importance of AQP1 in the basolateral membrane, we measured the rate of cell swelling initiated by decreasing peritubular osmolality as an indicator of water flux in microdissected TALs. Water flux was decreased by ∼50% in Aqp1 knockout mice compared with wild-types (4.0 ± 0.8 vs. 8.9 ± 1.7 fluorescent U/s, P < 0.02; n = 7). Furthermore, arginine vasopressin increased TAL AQP1 expression by 135 ± 17% (glycosylated) and 41 ± 11% (nonglycosylated; P < 0.01; n =5). We conclude that 1) the TAL expresses AQP1, 2) ∼23% of the total pool of AQP1 is localized to the basolateral membrane, 3) AQP1 mediates a significant portion of basolateral water flux, and 4) AQP1 is upregulated in TALs of rats infused with dDAVP. AQP1 could play an important role in regulation of TAL cell volume during changes in interstitial osmolality, such as during a high-salt diet or water deprivation. PMID:22674028

  5. Microcurrent Stimulation at Shenmen Acupoint Facilitates EEG Associated with Sleepiness and Positive Mood: A Randomized Controlled Electrophysiological Study

    PubMed Central

    Chan, Agnes S.; Yip, Joanne

    2015-01-01

    To examine the electrophysiological effects of microcurrent stimulation at the Shenmen acupoint, 40 healthy normal subjects were randomly assigned to a placebo group (sham stimulation) and an experimental group (bilateral electrocutaneous stimulation at the Shenmen). The following two electroencephalographic indicators were used to measure brain activity. (1) Arousal level was measured with reference to log-transformed absolute alpha power and power source and analyzed using low-resolution electromagnetic tomography and (2) frontal alpha asymmetry was used as an indicator of mood. After real stimulation for 10 minutes, absolute alpha power was globally reduced in the experimental group, particularly in the anterior and centrotemporal regions of the brain. This indicates a decline in the brain activity associated with arousal. Moreover, the reduction was more prominent in the left frontal region, as compared to the right frontal region, resulting in significant increase from negative to positive frontal alpha asymmetry scores and reflecting an increase in the brain activity associated with enhanced mood. However, the placebo group exhibited no significant changes in two indicators after sham stimulation. This study provides initial electrophysiological evidence of changes in brain activity associated with reduced arousal (and thus greater sleepiness) and enhanced mood after microcurrent stimulation at the Shenmen acupoint. PMID:25767551

  6. Microcurrent stimulation at shenmen acupoint facilitates EEG associated with sleepiness and positive mood: a randomized controlled electrophysiological study.

    PubMed

    Cheung, Mei-Chun; Chan, Agnes S; Yip, Joanne

    2015-01-01

    To examine the electrophysiological effects of microcurrent stimulation at the Shenmen acupoint, 40 healthy normal subjects were randomly assigned to a placebo group (sham stimulation) and an experimental group (bilateral electrocutaneous stimulation at the Shenmen). The following two electroencephalographic indicators were used to measure brain activity. (1) Arousal level was measured with reference to log-transformed absolute alpha power and power source and analyzed using low-resolution electromagnetic tomography and (2) frontal alpha asymmetry was used as an indicator of mood. After real stimulation for 10 minutes, absolute alpha power was globally reduced in the experimental group, particularly in the anterior and centrotemporal regions of the brain. This indicates a decline in the brain activity associated with arousal. Moreover, the reduction was more prominent in the left frontal region, as compared to the right frontal region, resulting in significant increase from negative to positive frontal alpha asymmetry scores and reflecting an increase in the brain activity associated with enhanced mood. However, the placebo group exhibited no significant changes in two indicators after sham stimulation. This study provides initial electrophysiological evidence of changes in brain activity associated with reduced arousal (and thus greater sleepiness) and enhanced mood after microcurrent stimulation at the Shenmen acupoint.

  7. Euclidean supergravity and multi-centered solutions

    NASA Astrophysics Data System (ADS)

    Sabra, W. A.

    2017-04-01

    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.

  8. Drosophila TDP-43 RNA-Binding Protein Facilitates Association of Sister Chromatid Cohesion Proteins with Genes, Enhancers and Polycomb Response Elements

    PubMed Central

    Misulovin, Ziva; Gause, Maria; Rickels, Ryan A; Shilatifard, Ali

    2016-01-01

    The cohesin protein complex mediates sister chromatid cohesion and participates in transcriptional control of genes that regulate growth and development. Substantial reduction of cohesin activity alters transcription of many genes without disrupting chromosome segregation. Drosophila Nipped-B protein loads cohesin onto chromosomes, and together Nipped-B and cohesin occupy essentially all active transcriptional enhancers and a large fraction of active genes. It is unknown why some active genes bind high levels of cohesin and some do not. Here we show that the TBPH and Lark RNA-binding proteins influence association of Nipped-B and cohesin with genes and gene regulatory sequences. In vitro, TBPH and Lark proteins specifically bind RNAs produced by genes occupied by Nipped-B and cohesin. By genomic chromatin immunoprecipitation these RNA-binding proteins also bind to chromosomes at cohesin-binding genes, enhancers, and Polycomb response elements (PREs). RNAi depletion reveals that TBPH facilitates association of Nipped-B and cohesin with genes and regulatory sequences. Lark reduces binding of Nipped-B and cohesin at many promoters and aids their association with several large enhancers. Conversely, Nipped-B facilitates TBPH and Lark association with genes and regulatory sequences, and interacts with TBPH and Lark in affinity chromatography and immunoprecipitation experiments. Blocking transcription does not ablate binding of Nipped-B and the RNA-binding proteins to chromosomes, indicating transcription is not required to maintain binding once established. These findings demonstrate that RNA-binding proteins help govern association of sister chromatid cohesion proteins with genes and enhancers. PMID:27662615

  9. Acute necrotizing pancreatitis: a multicenter study.

    PubMed

    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.

  10. Reductions in native grass biomass associated with drought facilitates the invasion of an exotic grass into a model grassland system.

    PubMed

    Manea, Anthony; Sloane, Daniel R; Leishman, Michelle R

    2016-05-01

    The invasion success of exotic plant species is often dependent on resource availability. Aspects of climate change such as rising atmospheric CO2 concentration and extreme climatic events will directly and indirectly alter resource availability in ecological communities. Understanding how these climate change-associated changes in resource availability will interact with one another to influence the invasion success of exotic plant species is complex. The aim of the study was to assess the establishment success of an invasive exotic species in response to climate change-associated changes in resource availability (CO2 levels and soil water availability) as a result of extreme drought. We grew grassland mesocosms consisting of four co-occurring native grass species common to the Cumberland Plain Woodland of western Sydney, Australia, under ambient and elevated CO2 levels and subjected them to an extreme drought treatment. We then added seeds of a highly invasive C3 grass, Ehrharta erecta, and assessed its establishment success (biomass production and reproductive output). We found that reduced biomass production of the native grasses in response to the extreme drought treatment enhanced the establishment success of E. erecta by creating resource pulses in light and space. Surprisingly, CO2 level did not affect the establishment success of E. erecta. Our results suggest that the invasion risk of grasslands in the future may be coupled to soil water availability and the subsequent response of resident native vegetation therefore making it strongly context- dependent.

  11. A Heart and A Mind: Self-distancing Facilitates the Association Between Heart Rate Variability, and Wise Reasoning

    PubMed Central

    Grossmann, Igor; Sahdra, Baljinder K.; Ciarrochi, Joseph

    2016-01-01

    Cardiac vagal tone (indexed via resting heart rate variability [HRV]) has been previously associated with superior executive functioning. Is HRV related to wiser reasoning and less biased judgments? Here we hypothesize that this will be the case when adopting a self-distanced (as opposed to a self-immersed) perspective, with self-distancing enabling individuals with higher HRV to overcome bias-promoting egocentric impulses and to reason wisely. However, higher HRV may not be associated with greater wisdom when adopting a self-immersed perspective. Participants were randomly assigned to reflect on societal issues from a self-distanced- or self-immersed perspective, with responses coded for reasoning quality. In a separate task, participants read about and evaluated a person performing morally ambiguous actions, with responses coded for dispositional vs. situational attributions. We simultaneously assessed resting cardiac recordings, obtaining six HRV indicators. As hypothesized, in the self-distanced condition, each HRV indicator was positively related to prevalence of wisdom-related reasoning (e.g., prevalence of recognition of limits of one’s knowledge, recognition that the world is in flux/change, consideration of others’ opinions and search for an integration of these opinions) and to balanced vs. biased attributions (recognition of situational and dispositional factors vs. focus on dispositional factors alone). In contrast, there was no relationship between these variables in the self-immersed condition. We discuss implications for research on psychophysiology, cognition, and wisdom. PMID:27092066

  12. CTNNBL1 facilitates the association of CWC15 with CDC5L and is required to maintain the abundance of the Prp19 spliceosomal complex

    PubMed Central

    van Maldegem, Febe; Maslen, Sarah; Johnson, Christopher M.; Chandra, Anita; Ganesh, Karuna; Skehel, Mark; Rada, Cristina

    2015-01-01

    In order to catalyse the splicing of messenger RNA, multiple proteins and RNA components associate and dissociate in a dynamic highly choreographed process. The Prp19 complex is a conserved essential part of the splicing machinery thought to facilitate the conformational changes the spliceosome undergoes during catalysis. Dynamic protein interactions often involve highly disordered regions that are difficult to study by structural methods. Using amine crosslinking and hydrogen–deuterium exchange coupled to mass spectrometry, we describe the architecture of the Prp19 sub-complex that contains CTNNBL1. Deficiency in CTNNBL1 leads to delayed initiation of cell division and embryonic lethality. Here we show that in vitro CTNNBL1 enhances the association of CWC15 and CDC5L, both core Prp19 complex proteins and identify an overlap in the region of CDC5L that binds either CTNNBL1 or CWC15 suggesting the two proteins might exchange places in the complex. Furthermore, in vivo, CTNNBL1 is required to maintain normal levels of the Prp19 complex and to facilitate the interaction of CWC15 with CDC5L. Our results identify a chaperone function for CTNNBL1 within the essential Prp19 complex, a function required to maintain the integrity of the complex and to support efficient splicing. PMID:26130721

  13. Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response.

    PubMed

    Pakchuen, Sujiraporn; Ishibashi, Mai; Takakusagi, Emi; Shirahige, Katsuhiko; Sutani, Takashi

    2016-08-12

    At the onset of anaphase, a protease called separase breaks the link between sister chromatids by cleaving the cohesin subunit Scc1. This irreversible step in the cell cycle is promoted by degradation of the separase inhibitor, securin, and polo-like kinase (Plk) 1-dependent phosphorylation of the Scc1 subunit. Plk could recognize substrates through interaction between its phosphopeptide interaction domain, the polo-box domain, and a phosphorylated priming site in the substrate, which has been generated by a priming kinase beforehand. However, the physiological relevance of this targeting mechanism remains to be addressed for many of the Plk1 substrates. Here, we show that budding yeast Plk1, Cdc5, is pre-deposited onto cohesin engaged in cohesion on chromosome arms in G2/M phase cells. The Cdc5-cohesin association is mediated by direct interaction between the polo-box domain of Cdc5 and Scc1 phosphorylated at multiple sites in its middle region. Alanine substitutions of the possible priming phosphorylation sites (scc1-15A) impair Cdc5 association with chromosomal cohesin, but they make only a moderate impact on mitotic cell growth even in securin-deleted cells (pds1Δ), where Scc1 phosphorylation by Cdc5 is indispensable. The same scc1-15A pds1Δ double mutant, however, exhibits marked sensitivity to the DNA-damaging agent phleomycin, suggesting that the priming phosphorylation of Scc1 poses an additional layer of regulation that enables yeast cells to adapt to genotoxic environments.

  14. Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis.

    PubMed

    Mishima, Kenichi; Kitoh, Hiroshi; Ohkawara, Bisei; Okuno, Tatsuya; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-12-01

    The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation.

  15. Human cytomegalovirus TRS1 protein associates with the 7-methylguanosine mRNA cap and facilitates translation.

    PubMed

    Ziehr, Benjamin; Lenarcic, Erik; Vincent, Heather A; Cecil, Chad; Garcia, Benjamin; Shenk, Thomas; Moorman, Nathaniel J

    2015-06-01

    Viruses rely on the host translation machinery for the synthesis of viral proteins. Human cells have evolved sensors that recognize viral RNAs and inhibit mRNA translation in order to limit virus replication. Understanding how viruses manipulate the host translation machinery to gain access to ribosomes and disable the antiviral response is therefore a critical aspect of the host/pathogen interface. In this study, we used a proteomics approach to identify human cytomegalovirus (HCMV) proteins that might contribute to viral mRNA translation. The HCMV TRS1 protein (pTRS1) associated with the 7-methylguanosine mRNA cap, increased the total level of protein synthesis, and colocalized with mRNAs undergoing translation initiation during infection. pTRS1 stimulated translation of a nonviral reporter gene and increased the translation of a reporter containing an HCMV 5' untranslated region (5'UTR) to a greater extent. The preferential effect of pTRS1 on translation of an mRNA containing a viral 5'UTR required the pTRS1 RNA and double-stranded RNA-dependent protein kinase (PKR)-binding domains, and was likely the result of PKR inhibition. However, pTRS1 also stimulated the total level of protein synthesis and translation directed by an HCMV 5'UTR in cells lacking PKR. Thus our results demonstrate that pTRS1 stimulates translation through both PKR-dependent and PKR-independent mechanisms.

  16. Wound Bed Preparation With a Dermal Substitute (Hyalomatrix® PA) Facilitates Re-epithelialization and Healing: Results of a Multicenter, Prospective, Observational Study on Complex Chronic Ulcers (The FAST Study).

    PubMed

    Caravaggi, Carlo; Grigoletto, Francesco; Scuderi, Nicolò

    2011-08-01

    The FAST study evaluated the performance and safety of Hyalomatrix® PA (a dermal substitute) in the treatment of chronic wounds of different etiology. This was a multicenter, prospective, observational study involving 70 Italian centers and 262 elderly patients. Patients were observed from the start of treatment with a dermal substitute (Hyalomatrix® PA [HPA]) until healthy dermal tissue suitable for a thin autograft was visible or until the growth of new epithelium from the wound edge was reported. Tracking the wound edge advancement was used to assess the dermal substitute's performance. The main endpoint was the reduction in threshold area (≥ 10%) of the ulcer. Treated ulcers were characterized as follows: 46% vascular, 25% diabetic foot, 12% traumatic wounds, 2% pressure ulcers and 15% other. Re-epithelization (≥ 10%) was achieved in 83% of ulcers in a median time of 16 days. Twenty-six percent (26%) of wounds achieved 75% re-epithelization within the 60-day follow-up period using only HPA treatment. A follow-up showed that 84% of ulcers achieved complete re-epithelialization by secondary intention. These findings indicate that HPA is a safe and effective dermal substitute. The results show that the re-epithelization process following HPA treatment is independent upon etiology, area, and depth of the ulcer, and treatment is more effective on acute ulcer formation.

  17. Ras-Association Domain Family 1 Isoform A (RASSF1A) Gene Polymorphism rs1989839 is Associated with Risk and Metastatic Potential of Osteosarcoma in Young Chinese Individuals: A Multi-Center, Case-Control Study

    PubMed Central

    Xu, Hongwei; Zhan, Wang; Chen, Zhiyuan

    2016-01-01

    Background The ras-association domain family 1 isoform A (RASSF1A) gene serves as a bona fide tumor suppressor gene. The polymorphisms in RASSF1A were previously reported to be associated with the risk of solid malignant tumors. We hypothesized herein that RASSF1A gene polymorphisms are involved in the risk and prognosis of osteosarcoma (OS). Material/Methods We recruited 279 young OS cases and 286 tumor-free controls from the east Chinese population. Five tagSNPs of RASSF1A gene (rs2236947A/C, rs2073497A/C, rs1989839C/T, rs72932987C/T, and rs4688728G/T) were genotyped. DNA was isolated from blood samples and then underwent PCR analysis for genotyping. Results rs1989839C/T is an important predictor of osteosarcoma risk and outcome. The CT genotype of rs1989839 is highly related to elevated risk of osteosarcoma. Furthermore, rs1989839C/T is also associated with the Enneking stage of osteosarcoma and risk of lung metastasis. One of the other 4 SNPs, rs2236947A/C, shows a borderline significance in predicting osteosarcoma risk. Conclusions Our study is the first to prove that RASSF1A gene polymorphisms may potentially be predictive for osteosarcoma risk and prognosis. PMID:27880743

  18. Multicenter Guidelines | Division of Cancer Prevention

    Cancer.gov

    A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

  19. The collagen triple helix repeat containing 1 facilitates hepatitis B virus-associated hepatocellular carcinoma progression by regulating multiple cellular factors and signal cascades.

    PubMed

    Zhang, Rui; Cao, Yanhua; Bai, Lan; Zhu, Chengliang; Li, Rui; He, Hui; Liu, Yingle; Wu, Kailang; Liu, Fang; Wu, Jianguo

    2015-12-01

    Hepatitis B virus (HBV) infection is one of the major causes of acute and chronic liver diseases, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCC accounts for more than 85% of primary liver cancers and is the seventh most common cancer and the third leading cause of cancer-related deaths. However, the mechanism by which HBV induces HCC is largely unknown. Collagen triple helixes repeat containing 1 (CTHRC1) is a secreted protein and has characteristics of a circulating hormone with potentially broad implications for cell metabolism and physiology. CTHRC1 is associated with human cancers, but its effect on HCC is unknown. Here, we revealed that CTHRC1 expression is highly correlated with HCC progression in HBV-infected patients, and demonstrated that HBV stimulates CTHRC1 expression by activating nuclear factor-kappa B (NF-κB) and cAMP response element binding protein (CREB), through extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/c-JNK) pathway. In addition, CTHRC1 activates hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) through regulating phosphoinosmde-3-kinase/protein kinase B/mammalian target of rapamycin (PI-3K/AKT/mTOR) pathway. More interestingly, CTHRC1 enhances colony formation, migration, and invasion of hepatoma cells by regulating p53 and stimulating matrix metalloproteinase-9 (MMP-9) expression. In addition, knock-down of CTHRC1 results in the repression of HBV-associated carcinogenesis in nude mice. Thus, we revealed a novel mechanism by which HBV facilitates HCC development through activating the oncoprotein CTHRC1, which in turn enhances HBV-related HCC progression by stimulates colony formation, migration, and invasion of hepatoma cells through regulating multiple cellular factors and signal cascades.

  20. Ethanol and drug findings in women consulting a Sexual Assault Center--associations with clinical characteristics and suspicions of drug-facilitated sexual assault.

    PubMed

    Hagemann, Cecilie T; Helland, Arne; Spigset, Olav; Espnes, Ketil A; Ormstad, Kari; Schei, Berit

    2013-08-01

    The purpose of the study was to describe toxicological findings among women seeking health care after sexual assault, and to assess the relationship with so-called proactive DFSA (drug facilitated sexual assault). We also explored associations between ethanol in blood/urine and background data, assault characteristics, and clinical findings. We conducted a retrospective, descriptive study of female patients ≥ 12 years of age consulting the Sexual Assault Center at St. Olavs University Hospital, Trondheim, Norway. They were examined between July 1, 2003 and December 31, 2010, and urine and/or blood were analyzed for ethanol and selected medicinal/recreational drugs. Among the 264 patients included, ethanol and/or drugs were detected in 155 (59%). Of the 50 patients (19%) testing positive for drugs other than ethanol, benzodiazepines/benzodiazepine-like drugs were found in 31, central stimulants in 14, cannabinoids in 13 and opioids in nine. None tested positive for gamma-hydroxybutyrate (GHB). In total, 57 patients (22%) suspected proactive DFSA, but only five had findings of sedative drugs that were not accounted for by self-reported voluntary intake. No cases could unequivocally be attributed to proactive DFSA. Among the 120 patients tested for ethanol within 12 h after the assault, 102 were positive. The median estimated blood alcohol concentration (BAC) at the time of assault was 1.87 g/L. Patients testing positive for ethanol more often reported a public place of assault and a stranger assailant. Higher estimated BAC at the time of assault was associated with higher frequency of suspecting proactive DFSA. Ethanol was the most prevalent toxicological finding in urine/blood from victims of sexual assault, and high ethanol concentrations were often detected. Among the patients suspecting proactive DFSA, very few had sedative drug findings not explained by voluntary intake. It seems like opportunistic DFSA, rather than proactive DFSA dominate among the sexually

  1. Facilitating Facilitators: Enhancing PBL through a Structured Facilitator Development Program

    ERIC Educational Resources Information Center

    Salinitri, Francine D.; Wilhelm, Sheila M.; Crabtree, Brian L.

    2015-01-01

    With increasing adoption of the problem-based learning (PBL) model, creative approaches to enhancing facilitator training and optimizing resources to maintain effective learning in small groups is essential. We describe a theoretical framework for the development of a PBL facilitator training program that uses the constructivist approach as the…

  2. Expression and Association of the Yersinia pestis Translocon Proteins, YopB and YopD, Are Facilitated by Nanolipoprotein Particles

    DOE PAGES

    Coleman, Matthew A.; Cappuccio, Jenny A.; Blanchette, Craig D.; ...

    2016-03-25

    Yersinia pestis enters host cells and evades host defenses, in part, through interactions between Yersinia pestis proteins and host membranes. One such interaction is through the type III secretion system, which uses a highly conserved and ordered complex for Yersinia pestis outer membrane effector protein translocation called the injectisome. The portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. The translocon is believed to form a pore allowing effector molecules to enter host cells. To facilitate mechanistic studies of the translocon, we have developed a cell-free approach for expressing translocon pore proteinsmore » as a complex supported in a bilayer membrane mimetic nano-scaffold known as a nanolipoprotein particle (NLP) Initial results show cell-free expression of Yersinia pestis outer membrane proteins YopB and YopD was enhanced in the presence of liposomes. However, these complexes tended to aggregate and precipitate. With the addition of co-expressed (NLP) forming components, the YopB and/or YopD complex was rendered soluble, increasing the yield of protein for biophysical studies. Biophysical methods such as Atomic Force Microscopy and Fluorescence Correlation Spectroscopy were used to confirm that the soluble YopB/D complex was associated with NLPs. An interaction between the YopB/D complex and NLP was validated by immunoprecipitation. The YopB/D translocon complex embedded in a NLP provides a platform for protein interaction studies between pathogen and host proteins. Ultimately, these studies will help elucidate the poorly understood mechanism which enables this pathogen to inject effector proteins into host cells, thus evading host defenses.« less

  3. Expression and Association of the Yersinia pestis Translocon Proteins, YopB and YopD, Are Facilitated by Nanolipoprotein Particles

    SciTech Connect

    Coleman, Matthew A.; Cappuccio, Jenny A.; Blanchette, Craig D.; Gao, Tingjuan; Arroyo, Erin S.; Hinz, Angela K.; Bourguet, Feliza A.; Segelke, Brent; Hoeprich, Paul D.; Huser, Thomas; Laurence, Ted A.; Motin, Vladimir L.; Chromy, Brett A.

    2016-03-25

    Yersinia pestis enters host cells and evades host defenses, in part, through interactions between Yersinia pestis proteins and host membranes. One such interaction is through the type III secretion system, which uses a highly conserved and ordered complex for Yersinia pestis outer membrane effector protein translocation called the injectisome. The portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. The translocon is believed to form a pore allowing effector molecules to enter host cells. To facilitate mechanistic studies of the translocon, we have developed a cell-free approach for expressing translocon pore proteins as a complex supported in a bilayer membrane mimetic nano-scaffold known as a nanolipoprotein particle (NLP) Initial results show cell-free expression of Yersinia pestis outer membrane proteins YopB and YopD was enhanced in the presence of liposomes. However, these complexes tended to aggregate and precipitate. With the addition of co-expressed (NLP) forming components, the YopB and/or YopD complex was rendered soluble, increasing the yield of protein for biophysical studies. Biophysical methods such as Atomic Force Microscopy and Fluorescence Correlation Spectroscopy were used to confirm that the soluble YopB/D complex was associated with NLPs. An interaction between the YopB/D complex and NLP was validated by immunoprecipitation. The YopB/D translocon complex embedded in a NLP provides a platform for protein interaction studies between pathogen and host proteins. Ultimately, these studies will help elucidate the poorly understood mechanism which enables this pathogen to inject effector proteins into host cells, thus evading host defenses.

  4. Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

    NASA Technical Reports Server (NTRS)

    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.

  5. Elliptic genera from multi-centers

    NASA Astrophysics Data System (ADS)

    Gaddam, Nava

    2016-05-01

    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} 4, the sextic in {W}{P} (2,1,1,1,1), the octic in {W}{P} (4,1,1,1,1) and the dectic in {W}{P} (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.

  6. An open multicenter comparative randomized clinical study on chitosan.

    PubMed

    Mo, Xiaohui; Cen, John; Gibson, Elaine; Wang, Robin; Percival, Steven L

    2015-01-01

    Chitosan, a natural polysaccharide derivate from chitin, offers a promising alternative biomaterial for use in wound dressings. In this work, the safety and efficacy of a next-generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied. This open multicenter comparative prospective randomized clinical study was conducted at three medical centers in China. A total of 90 patients (45 in test group and 45 in control group) with unhealed chronic wounds including pressure ulcers, vascular ulcers, diabetic foot ulcers, and wounds with minor infections, or at risk of infection, were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control. Baseline assessments were undertaken with the primary end point being wound area reduction. The secondary end points included pain reduction (using the NRS11 pain scale) at dressing change, wound exudate levels, wound depth and duration of the treatment. After 4 weeks treatment, the wound area reduction was significantly greater in the test group (65.97 ± 4.48%) than the control group (39.95 ± 4.48%). The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group. The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm. The level of exudate fell and the dressing could be removed integrally in both the test and control groups. The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days. No adverse events were reported in either group. In conclusion this open multicenter comparative prospective randomized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level. Furthermore the dressing was shown to be clinically safe and effective in the management

  7. Feasibility and variability of measuring the Lung Clearance Index in a multi-center setting.

    PubMed

    Fuchs, Susanne I; Ellemunter, Helmut; Eder, Johannes; Mellies, Uwe; Grosse-Onnebrink, Jörg; Tümmler, Burkhard; Staab, Doris; Jobst, Andrea; Griese, Matthias; Ripper, Jan; Rietschel, Ernst; Zeidler, Susanne; Ahrens, Frank; Gappa, Monika

    2012-07-01

    The Lung Clearance Index (LCI) is superior to spirometry in detecting early lung disease in cystic fibrosis (CF) and correlates with structural lung changes seen on CT scans. The LCI has the potential to become a novel outcome parameter for clinical and research purposes. However longitudinal studies are required to further prove its prognostic value. Multi-center design is likely to facilitate realization of such studies. Therefore the aim of the present study was to assess multi-center feasibility and inter-center variability of LCI measurements in healthy children and adolescents. Comparative measurements were performed in unselected patients with CF to confirm previous single-center results. LCI measurements were performed in eight centers using the EasyOne Pro, MBW Module (ndd Medical Technologies, Zurich, Switzerland). The overall success rate for LCI measurements was 75.5%, leaving 102/151 measurements in healthy volunteers and 139/183 measurements in patients with CF for final analysis. Age ranged between 4 and 24 years. Mean LCI (range of means among centers) was 6.3 (6.0-6.5) in healthy volunteers and thus normal. Inter-center variability of center means was 2.9%, ANOVA including Schffé procedure demonstrated no significant inter-center differences (P > 0.05). Mean LCI (range of means among centers) was 8.2 (7.4-8.9) in CF and thus abnormal. Our study demonstrates good multi-center feasibility and low inter-center variability of the LCI in healthy volunteers when measured with the EasyOne Pro MBW module. Our data confirm published LCI data in CF. However, central coordination, quality control, regular training, and supervision during the entire study appear essential for successfully performing multi-center trials.

  8. Some epidemiologic, clinical, microbiologic, and organizational assumptions that influenced the design and performance of the Global Enteric Multicenter Study (GEMS).

    PubMed

    Farag, Tamer H; Nasrin, Dilruba; Wu, Yukun; Muhsen, Khitam; Blackwelder, William C; Sommerfelt, Halvor; Panchalingam, Sandra; Nataro, James P; Kotloff, Karen L; Levine, Myron M

    2012-12-01

    The overall aim of the Global Enteric Multicenter Study-1 (GEMS-1) is to identify the etiologic agents associated with moderate-to-severe diarrhea (MSD) among children <5 years of age, and thereby the attributable pathogen-specific population-based incidence of MSD, to guide investments in research and public health interventions against diarrheal disease. To accomplish this, 9 core assumptions were vetted through widespread consultation: (1) a limited number of etiologic agents may be responsible for most MSD; (2) a definition of MSD can be crafted that encompasses cases that might otherwise be fatal in the community without treatment; (3) MSD seen at sentinel centers is a proxy for fatal diarrheal disease in the community; (4) matched case/control is the appropriate epidemiologic design; (5) methods across the sites can be standardized and rigorous quality control maintained; (6) a single 60-day postenrollment visit to case and control households creates mini-cohorts, allowing comparisons; (7) broad support for GEMS-1 messages can be achieved by incorporating advice from public health spokespersons; (8) results will facilitate the setting of investment and intervention priorities; and (9) wide acceptance and dissemination of the GEMS-1 results can be achieved.

  9. Some Epidemiologic, Clinical, Microbiologic, and Organizational Assumptions That Influenced the Design and Performance of the Global Enteric Multicenter Study (GEMS)

    PubMed Central

    Farag, Tamer H.; Nasrin, Dilruba; Wu, Yukun; Muhsen, Khitam; Blackwelder, William C.; Sommerfelt, Halvor; Panchalingam, Sandra; Nataro, James P.; Kotloff, Karen L.; Levine, Myron M.

    2012-01-01

    The overall aim of the Global Enteric Multicenter Study–1 (GEMS-1) is to identify the etiologic agents associated with moderate-to-severe diarrhea (MSD) among children <5 years of age, and thereby the attributable pathogen-specific population-based incidence of MSD, to guide investments in research and public health interventions against diarrheal disease. To accomplish this, 9 core assumptions were vetted through widespread consultation: (1) a limited number of etiologic agents may be responsible for most MSD; (2) a definition of MSD can be crafted that encompasses cases that might otherwise be fatal in the community without treatment; (3) MSD seen at sentinel centers is a proxy for fatal diarrheal disease in the community; (4) matched case/control is the appropriate epidemiologic design; (5) methods across the sites can be standardized and rigorous quality control maintained; (6) a single 60-day postenrollment visit to case and control households creates mini-cohorts, allowing comparisons; (7) broad support for GEMS-1 messages can be achieved by incorporating advice from public health spokespersons; (8) results will facilitate the setting of investment and intervention priorities; and (9) wide acceptance and dissemination of the GEMS-1 results can be achieved. PMID:23169935

  10. A Bayesian Approach to Multicenter Trials and Metaanalysis.

    ERIC Educational Resources Information Center

    Berry, Donald A.

    The use of a Bayesian approach in evaluating data from clinical trials with many treatment centers and from many studies is discussed. The main distinction between a metaanalysis and an analysis of a multicenter trial is that different studies may have very different designs, while the centers in a multicenter trial usually follow the same…

  11. Alcohol Consumption among University Students in North Rhine-Westphalia, Germany--Results from a Multicenter Cross-Sectional Study

    ERIC Educational Resources Information Center

    Akmatov, Manas K.; Mikolajczyk, Rafael T.; Meier, Sabine; Kramer, Alexander

    2011-01-01

    Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information…

  12. [Multicenter paragliding accident study 1990].

    PubMed

    Lautenschlager, S; Karli, U; Matter, P

    1992-01-01

    During the period from 1.1.90 until 31.12.90, 86 injuries associated with paragliding were analyzed in a prospective study in 12 different Swiss hospitals with reference to causes, patterns, and frequencies. The injuries showed a mean score of over 2 and were classified as severe. Most frequent spine injuries (36%) and lesions of the lower extremity (35%) with a high risk of the ankles were diagnosed. One accident was fatal. 60% of the accidents happened during landing, 26% during launching and 14% during flight. Half of the pilots were affected during their primary training course. Most accidents were caused by inflight error of judgement--especially incorrect estimation of wind conditions--and further the choice of unfavourable landing sites. In contrast to previous injury-reports, only one equipment failure could be noted, but often the equipment was not corresponding with the experience and the weight of the pilot. To reduce the frequency of paragliding-injuries an accurate choice of equipment and an increased attention to environmental factors is mandatory. Furthermore an education-program regarding the attitude and intelligence of the pilot should be included in training courses.

  13. Fungal phylogenetic diversity drives plant facilitation.

    PubMed

    Montesinos-Navarro, Alicia; Segarra-Moragues, J G; Valiente-Banuet, A; Verdú, M

    2016-06-01

    Plant-plant facilitation is a crucial ecological process, as many plant species (facilitated) require the presence of an established individual (nurse) to recruit. Some plant facilitative interactions disappear during the ontogenetic development of the facilitated plant but others persist, even when the two plants are adults. We test whether the persistence of plant facilitative interactions is explained by the phylogenetic diversity of mutualistic and non-mutualistic fungi that the nurse and the facilitated species add to the shared rhizosphere. We classify plant facilitative interactions as persistent and non-persistent interactions and quantify the phylogenetic diversity of mutualistic and non-mutualistic fungi added by the plant species to the shared rhizosphere. Our results show that the facilitated species add less phylogenetic diversity of non-mutualistic fungi when plant facilitative interactions persist than when they do not persist. However, persistent and non-persistent facilitative interactions did not differ in the phylogenetic diversity of mutualistic fungi added by the facilitated species to the shared rhizosphere. Finally, the fungal phylogenetic diversity added by the nurse to the shared rhizosphere did not differ between persistent and non-persistent interactions. This study suggests that considering the fungal associates of the plant species involved in facilitative interactions can shed light on the mechanisms of persistence for plant-plant interactions.

  14. Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

    PubMed Central

    Jakubowska, A; Rozkrut, D; Antoniou, A; Hamann, U; Scott, R J; McGuffog, L; Healy, S; Sinilnikova, O M; Rennert, G; Lejbkowicz, F; Flugelman, A; Andrulis, I L; Glendon, G; Ozcelik, H; Thomassen, M; Paligo, M; Aretini, P; Kantala, J; Aroer, B; von Wachenfeldt, A; Liljegren, A; Loman, N; Herbst, K; Kristoffersson, U; Rosenquist, R; Karlsson, P; Stenmark-Askmalm, M; Melin, B; Nathanson, K L; Domchek, S M; Byrski, T; Huzarski, T; Gronwald, J; Menkiszak, J; Cybulski, C; Serrano, P; Osorio, A; Cajal, T R; Tsitlaidou, M; Benítez, J; Gilbert, M; Rookus, M; Aalfs, C M; Kluijt, I; Boessenkool-Pape, J L; Meijers-Heijboer, H E J; Oosterwijk, J C; van Asperen, C J; Blok, M J; Nelen, M R; van den Ouweland, A M W; Seynaeve, C; van der Luijt, R B; Devilee, P; Easton, D F; Peock, S; Frost, D; Platte, R; Ellis, S D; Fineberg, E; Evans, D G; Lalloo, F; Eeles, R; Jacobs, C; Adlard, J; Davidson, R; Eccles, D; Cole, T; Cook, J; Godwin, A; Bove, B; Stoppa-Lyonnet, D; Caux-Moncoutier, V; Belotti, M; Tirapo, C; Mazoyer, S; Barjhoux, L; Boutry-Kryza, N; Pujol, P; Coupier, I; Peyrat, J-P; Vennin, P; Muller, D; Fricker, J-P; Venat-Bouvet, L; Johannsson, O Th; Isaacs, C; Schmutzler, R; Wappenschmidt, B; Meindl, A; Arnold, N; Varon-Mateeva, R; Niederacher, D; Sutter, C; Deissler, H; Preisler-Adams, S; Simard, J; Soucy, P; Durocher, F; Chenevix-Trench, G; Beesley, J; Chen, X; Rebbeck, T; Couch, F; Wang, X; Lindor, N; Fredericksen, Z; Pankratz, V S; Peterlongo, P; Bonanni, B; Fortuzzi, S; Peissel, B; Szabo, C; Mai, P L; Loud, J T; Lubinski, J

    2012-01-01

    Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID:22669161

  15. The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers.

    PubMed

    Jakubowska, Anna; Rozkrut, Dominik; Antoniou, Antonis; Hamann, Ute; Lubinski, Jan

    2010-06-01

    Integrins containing the beta(3) subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the beta(3) subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the ITGB3 polymorphism was associated with an increased risk of ovarian cancer for BRCA1 mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00-1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96-1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for BRCA2 mutation carriers (HR 1.09, 95% CI 0.89-1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

  16. Multicenter Epidemiological Studies of Atherosclerosis Imaging

    PubMed Central

    Liu, Songtao; Bluemke, David A.

    2011-01-01

    Cardiovascular disease is the leading course of death and disability. Conventional cardiac risk factors do not fully explain the level of cardiovascular risk, incidence of coronary artery disease, and coronary events. Risk stratification and therapy based solely on these conventional risk factors may overlook a population who would benefit from lifestyle and risk factor modification. Thus, research has recently focused on improving risk assessment with new tools in an effort to better identify subjects at highest risk and in need of aggressive management. Cardiovascular imaging, both in coronary and extracoronary arterial beds, has proven to be very helpful in this regard. In this article, we review the current literature from multicenter epidemiology studies on the utility of noninvasive imaging modalities for risk stratification in the context of conventional risk factor evaluation. PMID:20805734

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

    SciTech Connect

    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

  18. Facilitating Organizational Change.

    ERIC Educational Resources Information Center

    1999

    The first of the three papers in this symposium, "Conflicts that Arise in Small Group Facilitation: A Descriptive Study of Accounts, Actions, Outcomes, and Assessments" (Judith A. Kolb, William J. Rothwell), contains self-report verbatim accounts contributed by facilitators and the results of a literature review on small group conflict.…

  19. Evaluator or Facilitator.

    ERIC Educational Resources Information Center

    Bolding, James T.

    1978-01-01

    In American schools, the classroom teacher must act in two conflicting capacities: as a facilitator of learning and as an evaluator of his own facilitating activities. To avoid problems inherent in this, the evaluator role could be assigned elsewhere, as in the Boy Scouts' merit badge system. (SJL)

  20. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    DTIC Science & Technology

    2015-12-01

    Award Number: W81XWH-10-1-0894 TITLE: Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration PRINCIPAL...DATES COVERED 15Sep2010 - 14Sep2015 4. TITLE AND SUBTITLE Multicenter Clinical Trial of Keratin Biomaterial for 5a. CONTRACT NUMBER W81XWH-10-1-0894... clinical trial was to be initiated as soon as the FDA provided an IND for the keratin biomaterial hydrogel. However, due to delays in the FDA approval

  1. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    PubMed Central

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    Objective The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. Materials and methods A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Results Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05), and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006). A decrease in vWF was seen in the female population consuming nattokinase (P<0.1). In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h), an increase was seen for 66% of the people after 8-week consumption of nattokinase (P<0.1), in contrast to only 8% in the placebo group. Conclusion The data suggest that nattokinase consumption in a North American population is associated with beneficial

  2. Multicenter Comparison of Laboratory Performance in Cytomegalovirus and Epstein-Barr Virus Viral Load Testing using International Standards

    PubMed Central

    Rychert, Jenna; Danziger-Isakov, Lara; Yen-Lieberman, Belinda; Storch, Gregory; Buller, Richard; Sweet, Stewart C.; Mehta, Aneesh K.; Cheeseman, Jennifer A.; Heeger, Peter; Rosenberg, Eric S.; Fishman, Jay A.

    2015-01-01

    Background Infections with cytomegalovirus (CMV) and Epstein Barr Virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation (CTOT/CTOTC). Methods Viral load testing was performed on well-defined viral preparations according to standard operating procedures at each site. Results Among centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. EBV viral load data were more variable and less accurate despite the use of international standards. Conclusions These data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated by using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials. PMID:25303316

  3. Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

    PubMed Central

    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

  4. Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study

    PubMed Central

    Cabibbe, Andrea M.; Feuerriegel, Silke; Casali, Nicola; Drobniewski, Francis; Rodionova, Yulia; Bakonyte, Daiva; Stakenas, Petras; Pimkina, Edita; Augustynowicz-Kopeć, Ewa; Degano, Massimo; Ambrosi, Alessandro; Hoffner, Sven; Mansjö, Mikael; Werngren, Jim; Rüsch-Gerdes, Sabine; Niemann, Stefan; Cirillo, Daniela M.

    2014-01-01

    ABSTRACT Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZAr). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZAr strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZAr strains, (iii) mutations with an unclear role found in less than 70% of PZAr strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZAr; the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. PMID:25336456

  5. Parietal connectivity mediates multisensory facilitation.

    PubMed

    Brang, David; Taich, Zachary J; Hillyard, Steven A; Grabowecky, Marcia; Ramachandran, V S

    2013-09-01

    Our senses interact in daily life through multisensory integration, facilitating perceptual processes and behavioral responses. The neural mechanisms proposed to underlie this multisensory facilitation include anatomical connections directly linking early sensory areas, indirect connections to higher-order multisensory regions, as well as thalamic connections. Here we examine the relationship between white matter connectivity, as assessed with diffusion tensor imaging, and individual differences in multisensory facilitation and provide the first demonstration of a relationship between anatomical connectivity and multisensory processing in typically developed individuals. Using a whole-brain analysis and contrasting anatomical models of multisensory processing we found that increased connectivity between parietal regions and early sensory areas was associated with the facilitation of reaction times to multisensory (auditory-visual) stimuli. Furthermore, building on prior animal work suggesting the involvement of the superior colliculus in this process, using probabilistic tractography we determined that the strongest cortical projection area connected with the superior colliculus includes the region of connectivity implicated in our independent whole-brain analysis.

  6. Facilitating Understandings of Geometry.

    ERIC Educational Resources Information Center

    Pappas, Christine C.; Bush, Sara

    1989-01-01

    Illustrates some learning encounters for facilitating first graders' understanding of geometry. Describes some of children's approaches using Cuisenaire rods and teacher's intervening. Presents six problems involving various combinations of Cuisenaire rods and cubes. (YP)

  7. Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy Versus Fluocinolone Acetonide Intraocular Implant for Intermediate, Posterior or Panuveitis: 54 month results of The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study

    PubMed Central

    Kempen, John H.; Altaweel, Michael M.; Drye, Lea T.; Holbrook, Janet T.; Jabs, Douglas A.; Sugar, Elizabeth A.; Thorne, Jennifer E.

    2015-01-01

    fluocinolone acetonide implant therapy is associated with a clinically important increased risk of glaucoma and cataract with respect to systemic therapy, suggesting that careful monitoring and early intervention to prevent glaucoma is warranted with implant therapy. Systemic therapy subjects avoided a significant excess of toxicities of systemic corticosteroid and immunosuppressive therapies in the trial. Self-reported QoL measures initially favored implant therapy, but over time the measures converged, with generally favorable QoL in both groups. PMID:26298718

  8. LZAP Inhibits p38 MAPK (p38) Phosphorylation and Activity by Facilitating p38 Association with the Wild-Type p53 Induced Phosphatase 1 (WIP1)

    PubMed Central

    An, Hanbing; Lu, Xinyuan; Liu, Dan; Yarbrough, Wendell G.

    2011-01-01

    LZAP (Cdk5rap3, C53) is a putative tumor suppressor that inhibits RelA, Chk1 and Chk2 and activates p53. LZAP is lost in a portion of human head and neck squamous cell carcinoma and experimental loss of LZAP expression is associated with enhanced invasion, xenograft tumor growth and angiogenesis. p38 MAPK can increase or decrease proliferation and cell death depending on cellular context. LZAP has no known enzymatic activity, implying that its biological functions are likely mediated by its protein-protein interactions. To gain further insight into LZAP activities, we searched for LZAP-associated proteins (LAPs). Here we show that the LZAP binds p38, alters p38 cellular localization, and inhibits basal and cytokine-stimulated p38 activity. Expression of LZAP inhibits p38 phosphorylation in a dose-dependent fashion while loss of LZAP enhances phosphorylation and activation with resultant phosphorylation of p38 downstream targets. Mechanistically, the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1. Expression of LZAP increased both LZAP and Wip1 binding to p38. Taken together, these data suggest that LZAP activity includes inhibition of p38 phosphorylation and activation. PMID:21283629

  9. LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 association with the wild-type p53 induced phosphatase 1 (WIP1).

    PubMed

    An, Hanbing; Lu, Xinyuan; Liu, Dan; Yarbrough, Wendell G

    2011-01-24

    LZAP (Cdk5rap3, C53) is a putative tumor suppressor that inhibits RelA, Chk1 and Chk2 and activates p53. LZAP is lost in a portion of human head and neck squamous cell carcinoma and experimental loss of LZAP expression is associated with enhanced invasion, xenograft tumor growth and angiogenesis. p38 MAPK can increase or decrease proliferation and cell death depending on cellular context. LZAP has no known enzymatic activity, implying that its biological functions are likely mediated by its protein-protein interactions. To gain further insight into LZAP activities, we searched for LZAP-associated proteins (LAPs). Here we show that the LZAP binds p38, alters p38 cellular localization, and inhibits basal and cytokine-stimulated p38 activity. Expression of LZAP inhibits p38 phosphorylation in a dose-dependent fashion while loss of LZAP enhances phosphorylation and activation with resultant phosphorylation of p38 downstream targets. Mechanistically, the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1. Expression of LZAP increased both LZAP and Wip1 binding to p38. Taken together, these data suggest that LZAP activity includes inhibition of p38 phosphorylation and activation.

  10. Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway

    PubMed Central

    Tao, Leilei; Huang, Guichun; Wang, Rui; Pan, Yan; He, Zhenyue; Chu, Xiaoyuan; Song, Haizhu; Chen, Longbang

    2016-01-01

    Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. Furthermore, it was also observed that IL-11 induced STAT3 phosphorylation and increased anti-apoptotic protein Bcl-2 and Survivin expression in cancer cells. The effect could be abrogated by suppressing STAT3 phosphorylation or silencing IL-11Rα expression in cancer cells. In conclusion, chemotherapy-induced IL-11 upregulation in CAF promotes lung adenocarcinoma cell chemoresistance by activating IL-11R/STAT3 anti-apoptotic signaling pathway. PMID:27922075

  11. The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

    PubMed

    Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

    2015-11-20

    Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.

  12. Extremal multicenter black holes: nilpotent orbits and Tits Satake universality classes

    NASA Astrophysics Data System (ADS)

    Fré, Pietro; Sorin, Alexander S.

    2013-01-01

    Four dimensional supergravity theories whose scalar manifold is a symmetric coset manifold UD=4/Hc are arranged into a finite list of Tits Satake universality classes. Stationary solutions of these theories, spherically symmetric or not, are identified with those of an euclidian three-dimensional σ-model, whose target manifold is a Lorentzian coset UD=3/H* and the extremal ones are associated with H* nilpotent orbits in the K* representation emerging from the orthogonal decomposition of the algebra {U} D=3 with respect to H*. It is shown that the classification of such orbits can always be reduced to the Tits-Satake projection and it is a class property of the Tits Satake universality classes. The construction procedure of Bossard et al of extremal multicenter solutions by means of a triangular hierarchy of integrable equations is completed and converted into a closed algorithm by means of a general formula that provides the transition from the symmetric to the solvable gauge. The question of the relation between H* orbits and charge orbits W of the corresponding black holes is addressed and also reduced to the corresponding question within the Tits Satake projection. It is conjectured that on the vanishing locus of the Taub-NUT current the relation between H*-orbit and W-orbit is rigid and one-to-one. All black holes emerging from multicenter solutions associated with a given H* orbit have the same W-type. For the S 3 model we provide a complete survey of its multicenter solutions associated with all of the previously classified nilpotent orbits of {s}{l}(2)× {s}{l}(2) within {{{g}}_{2,2 }} . We find a new intrinsic classification of the W-orbits of this model that might provide a paradigm for the analogous classification in all the other Tits Satake universality classes.

  13. Pharmacotherapy of elderly patients in everyday anthroposophic medical practice: a prospective, multicenter observational study

    PubMed Central

    2010-01-01

    Background Pharmacotherapy in the older adult is a complex field involving several different medical professionals. The evidence base for pharmacotherapy in elderly patients in primary care relies on only a few clinical trials, thus documentation must be improved, particularly in the field of complementary and alternative medicine (CAM) like phytotherapy, homoeopathy, and anthroposophic medicine. This study describes diagnoses and therapies observed in elderly patients treated with anthroposophic medicine in usual care. Methods Twenty-nine primary care physicians in Germany participated in this prospective, multicenter observational study on prescribing patterns. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients were at least 60 years of age. Multiple logistic regression analysis was used to determine factors associated with anthroposophic prescriptions. Results In 2005, a total of 12 314 prescriptions for 3076 patients (68.1% female) were included. The most frequent diagnoses were hypertension (11.1%), breast cancer (3.5%), and heart failure (3.0%). In total, 30.5% of the prescriptions were classified as CAM remedies alone, 54.4% as conventional pharmaceuticals alone, and 15.1% as a combination of both. CAM remedies accounted for 41.7% of all medications prescribed (35.5% anthroposophic). The adjusted odds ratio (AOR) for receiving an anthroposophic remedy was significantly higher for the first consultation (AOR = 1.65; CI: 1.52-1.79), treatment by an internist (AOR = 1.49; CI: 1.40-1.58), female patients (AOR = 1.35; CI: 1.27-1.43), cancer (AOR = 4.54; CI: 4.12-4.99), arthropathies (AOR = 1.36; CI: 1.19-1.55), or dorsopathies (AOR = 1.34; CI: 1.16-1.55) and it decreased with patient age (AOR = 0.97; CI: 0.97-0.98). The likelihood of being prescribed an anthroposophic remedy was especially low for patients with hypertensive diseases (AOR = 0.36; CI: 0.32-0.39), diabetes mellitus (AOR = 0.17; CI: 0.14-0.22), or

  14. A multicenter study to standardize reporting and analyses of fluorescence-activated cell-sorted murine intestinal epithelial cells

    PubMed Central

    Magness, Scott T.; Puthoff, Brent J.; Crissey, Mary Ann; Dunn, James; Henning, Susan J.; Houchen, Courtney; Kaddis, John S.; Kuo, Calvin J.; Li, Linheng; Lynch, John; Martin, Martin G.; May, Randal; Niland, Joyce C.; Olack, Barbara; Qian, Dajun; Stelzner, Matthias; Swain, John R.; Wang, Fengchao; Wang, Jiafang; Wang, Xinwei; Yan, Kelley; Yu, Jian

    2013-01-01

    Fluorescence-activated cell sorting (FACS) is an essential tool for studies requiring isolation of distinct intestinal epithelial cell populations. Inconsistent or lack of reporting of the critical parameters associated with FACS methodologies has complicated interpretation, comparison, and reproduction of important findings. To address this problem a comprehensive multicenter study was designed to develop guidelines that limit experimental and data reporting variability and provide a foundation for accurate comparison of data between studies. Common methodologies and data reporting protocols for tissue dissociation, cell yield, cell viability, FACS, and postsort purity were established. Seven centers tested the standardized methods by FACS-isolating a specific crypt-based epithelial population (EpCAM+/CD44+) from murine small intestine. Genetic biomarkers for stem/progenitor (Lgr5 and Atoh 1) and differentiated cell lineages (lysozyme, mucin2, chromogranin A, and sucrase isomaltase) were interrogated in target and control populations to assess intra- and intercenter variability. Wilcoxon's rank sum test on gene expression levels showed limited intracenter variability between biological replicates. Principal component analysis demonstrated significant intercenter reproducibility among four centers. Analysis of data collected by standardized cell isolation methods and data reporting requirements readily identified methodological problems, indicating that standard reporting parameters facilitate post hoc error identification. These results indicate that the complexity of FACS isolation of target intestinal epithelial populations can be highly reproducible between biological replicates and different institutions by adherence to common cell isolation methods and FACS gating strategies. This study can be considered a foundation for continued method development and a starting point for investigators that are developing cell isolation expertise to study physiology and

  15. Wandering spleen in children: multicenter retrospective study.

    PubMed

    Fiquet-Francois, Caroline; Belouadah, Mohamed; Ludot, Hugues; Defauw, Benoit; Mcheik, Jiad Noel; Bonnet, Jean Paul; Kanmegne, Charly Udozen; Weil, Dominique; Coupry, Lionel; Fremont, Benjamin; Becmeur, Francois; Lacreuse, Isabelle; Montupet, Philippe; Rahal, Eliane; Botto, Nathalie; Cheikhelard, Alaa; Sarnacki, Sabine; Petit, Thierry; Poli Merol, Marie Laurence

    2010-07-01

    Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

  16. Microtubule-Associated Protein SBgLR Facilitates Storage Protein Deposition and Its Expression Leads to Lysine Content Increase in Transgenic Maize Endosperm

    PubMed Central

    Liu, Chen; Li, Shixue; Yue, Jing; Xiao, Wenhan; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2015-01-01

    Maize (Zea mays) seed is deficient in protein and lysine content. Many studies have been made to improve the nutritional quality of maize seeds. Previously, we reported the role of a natural lysine-rich protein gene SBgLR in increasing protein and lysine content. However, how the SBgLR improves lysine and protein content remains unclear. Here, the reasons and possible mechanism for SBgLR in protein and lysine improvement have been analyzed and discussed. Through seed-specific expression of SBgLR, we obtained transgenic maize with the simultaneously increased lysine and protein contents. High-protein and high-lysine characters were stably inherited across generations. The expression of SBgLR in maize kernels increased the accumulation of both zeins and non-zein proteins. Transmission electron microscopy showed that the number of protein bodies (PBs) was increased obviously in SBgLR transgenic immature endosperms with the morphology and structure of PBs unchanged. The proteinaceous matrix was more abundant in transgenic mature endosperms under scanning electron microscopy. The stabilities of zein and lysine-rich non-zein genes were also increased in transgenic endosperms. Finally, the potential application of SBgLR in maize nutrient improvement was evaluated. This study shows that a cytoskeleton-associated protein has potential applicable value in crop nutrient improving, and provided a feasible strategy for improvement of maize grain quality. PMID:26703573

  17. Phosphatidic acid and phosphoinositides facilitate liposome association of Yas3p and potentiate derepression of ARE1 (alkane-responsive element one)-mediated transcription control.

    PubMed

    Kobayashi, Satoshi; Hirakawa, Kiyoshi; Horiuchi, Hiroyuki; Fukuda, Ryouichi; Ohta, Akinori

    2013-12-01

    In the n-alkane assimilating yeast Yarrowia lipolytica, the expression of ALK1, encoding a cytochrome P450 that catalyzes terminal mono-oxygenation of n-alkanes, is induced by n-alkanes. The transcription of ALK1 is regulated by a heterocomplex that comprises the basic helix-loop-helix transcription activators, Yas1p and Yas2p, and binds to alkane-responsive element 1 (ARE1) in the ALK1 promoter. An Opi1 family transcription repressor, Yas3p, represses transcription by binding to Yas2p. Yas3p localizes in the nucleus when Y. lipolytica is grown on glucose but localizes to the endoplasmic reticulum (ER) upon the addition of n-alkanes. In this study, we showed that recombinant Yas3p binds to the acidic phospholipids, phosphatidic acid (PA) and phosphoinositides (PIPs), in vitro. The ARE1-mediated transcription was enhanced in vivo in mutants defective in an ortholog of the Saccharomyces cerevisiae gene PAH1, encoding PA phosphatase, and in an ortholog of SAC1, encoding PIP phosphatase in the ER. Truncation mutation analyses for Yas3p revealed two regions that bound to PA and PIPs. These results suggest that the interaction with acidic phospholipids is important for the n-alkane-induced association of Yas3p with the ER membrane.

  18. Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association.

    PubMed

    Little, Kevin D; Hemler, Martin E; Stipp, Christopher S

    2004-05-01

    By means of a variety of intracellular scaffolding proteins, a vast number of heterotrimeric G protein-coupled receptors (GPCRs) may achieve specificity in signaling through a much smaller number of heterotrimeric G proteins. Members of the tetraspanin family organize extensive complexes of cell surface proteins and thus have the potential to act as GPCR scaffolds; however, tetraspanin-GPCR complexes had not previously been described. We now show that a GPCR, GPR56/TM7XN1, and heterotrimeric G protein subunits, Galpha(q), Galpha(11), and Gbeta, associate specifically with tetraspanins and CD81, but not with other tetraspanins. CD9 Complexes of GPR56 with CD9 and CD81 remained intact when fully solubilized and were resistant to cholesterol depletion. Hence they do not depend on detergent-insoluble, raft-like membrane microdomains for stability. A central role for CD81 in promoting or stabilizing a GPR56-CD81-Galpha(q/11) complex was revealed by CD81 immunodepletion and reexpression experiments. Finally, antibody engagement of cell surface CD81 or cell activation with phorbol ester revealed two distinct mechanisms by which GPR56-CD81-Galpha(q/11) complexes can be dynamically regulated. These data reveal a potential role for tetraspanins CD9 and CD81 as GPCR scaffolding proteins.

  19. A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning

    PubMed Central

    Mang, Cameron S.; Snow, Nicholas J.; Campbell, Kristin L.; Ross, Colin J. D.

    2014-01-01

    The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recruitment curves generated with transcranial magnetic stimulation showed larger increases when PAS was preceded by aerobic exercise (59.8% increase) compared with rest (14.2% increase, P = 0.02). Time lag of CT task performance on the repeated sequence improved under the aerobic exercise condition from early (−100.8 ms) to late practice (−75.2 ms, P < 0.001) and was maintained at retention (−79.2 ms, P = 0.004) but did not change under the rest condition (P > 0.16). Systemic BDNF increased on average by 3.4-fold following aerobic exercise (P = 0.003), but the changes did not relate to neurophysiological or behavioral measures (P > 0.42). These results indicate that a single bout of high-intensity aerobic exercise can prime LTP-like neuroplasticity and promote sequence-specific implicit motor learning. PMID:25257866

  20. Overexpression of the long non-coding RNA, linc-UBC1, is associated with poor prognosis and facilitates cell proliferation, migration, and invasion in colorectal cancer

    PubMed Central

    Gao, Xunfeng; Wen, Jianfan; Gao, Peng; Zhang, Guowei; Zhang, Gangqing

    2017-01-01

    Long non-coding RNAs (lncRNAs) serve comprehensive roles in various diseases, including cancer. lncRNA upregulated in bladder cancer 1 (linc-UBC1) is a notable biomarker of prognosis in certain cancer types; however, its involvement in the progression of colorectal cancer (CRC) remains unknown. The present study aimed to investigate the expression of linc-UBC1 in patients with CRC and to investigate its effect on CRC cells. The expression levels of linc-UBC1 were estimated by reverse transcription-quantitative polymerase chain reaction in clinical CRC specimens and matched adjacent non-tumor mucosa from 96 cases of CRC, as well as in a number of CRC cell lines. In addition, the biological roles of linc-UBC1 were examined using a cell counting kit-8 assay, flow cytometry, and migration and invasion assays following the downregulation of linc-UBC1 by small interfering RNA. The results revealed that linc-UBC1 was significantly overexpressed in CRC tissues and the majority of CRC cell lines compared with the matched non-tumor mucosa and normal intestinal epithelial cells. Furthermore, high expression levels of linc-UBC1 were significantly associated with large tumor size, greater tumor depth, lymph node metastasis, and advanced tumor-node-metastasis stages. Patients with abnormal expression of linc-UBC1 had poorer overall survival times according to Kaplan–Meier analyses. Furthermore, multivariate Cox regression analysis indicated that linc-UBC1 was a significant independent prognostic factor. The results also revealed that reducing the expression of linc-UBC1 led to the inhibition of migration, invasion, and proliferation of CRC cells in vitro. Taken together, the results of the present study suggest that overexpression of linc-UBC1 promotes proliferation and metastasis in CRC, and may be considered as a novel diagnostic marker of CRC. PMID:28260919

  1. A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning.

    PubMed

    Mang, Cameron S; Snow, Nicholas J; Campbell, Kristin L; Ross, Colin J D; Boyd, Lara A

    2014-12-01

    The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recruitment curves generated with transcranial magnetic stimulation showed larger increases when PAS was preceded by aerobic exercise (59.8% increase) compared with rest (14.2% increase, P = 0.02). Time lag of CT task performance on the repeated sequence improved under the aerobic exercise condition from early (-100.8 ms) to late practice (-75.2 ms, P < 0.001) and was maintained at retention (-79.2 ms, P = 0.004) but did not change under the rest condition (P > 0.16). Systemic BDNF increased on average by 3.4-fold following aerobic exercise (P = 0.003), but the changes did not relate to neurophysiological or behavioral measures (P > 0.42). These results indicate that a single bout of high-intensity aerobic exercise can prime LTP-like neuroplasticity and promote sequence-specific implicit motor learning.

  2. [Drug facilitated sexual assault].

    PubMed

    Alempijević, Djordje; Savić, Slobodan; Stojanović, Jovan; Spasić, Andjelka

    2007-01-01

    In line with the fact that there is little information regarding drug facilitated sexual assault in national medical literature, the authors aimed to prepare a review of the phenomenon based on available international references. Therefore we offered a definition of the concept of sexual assault, and rape in particular. Consent and ability for valid consent for sexual intercourse were defined as well. A review contains discussion about the basic elements of a concept of drug-facilitated sexual assault. There is also available information in regard to pharmacology of common data rape drugs, i.e. flunitrazepam, gamma-hydroxybutyrate (GHB), and ketamine. We indicate the utmost importance of prompt collecting of biological samples for toxicological screening in patients who are suspected victims of drug facilitated sexual assault.

  3. Understanding Facilitation: Theory and Principles.

    ERIC Educational Resources Information Center

    Hogan, Christine

    This book introduces newcomers to the concept of facilitation, and it presents a critical analysis of established and current theory on facilitation for existing practitioners. The following are among the topics discussed: (1) emergence of the field of facilitation; (2) development of facilitation in management; (3) development of facilitation in…

  4. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  5. Facilitator's Guide: Censorship Workshop.

    ERIC Educational Resources Information Center

    Layden, Kent

    To help leaders or "facilitators" of a series of simulation exercises on controversial issues for school board members, this guide describes how the simulations work and provides some of the materials required for the simulation exercise on censorship and book banning. After defining simulation or gaming exercises, the author notes the…

  6. Facilitating Distance Education.

    ERIC Educational Resources Information Center

    Rossman, Mark H., Ed.; Rossman, Maxine E., Ed.

    1995-01-01

    This collection of articles on distance learning reflects the perspectives and concerns of the learner and the facilitator of learning in distance education setting. Eight chapters are included: (1) "The Evolution and Advantages of Distance Education" (John E. Cantelon) traces the history of distance education and demonstrates how it transcends…

  7. Facilitative Strategies in Action.

    ERIC Educational Resources Information Center

    Fuller, Thara M. A.; Haugabrook, Adrian K.

    2001-01-01

    Describes campus-based strategies to facilitate collaboration by examining the process of restructuring a division of student affairs as an educational partner with academic affairs. Describes three collaborative efforts at the University of Massachusetts Boston: the Beacon Leadership Project, the Diversity Research Initiative, and the Beacon…

  8. The Inclusion Facilitator's Guide

    ERIC Educational Resources Information Center

    Jorgensen, Cheryl M.; Schuh, Mary C.; Nisbet, Jan

    2005-01-01

    Inclusion facilitators are educators who do more than teach children with disabilities--they advocate for change in schools and communities, sparking a passion for inclusion in teachers, administrators, and families and giving them the practical guidance they need to make it work. This is an essential new role in today's schools, and this guide…

  9. Re-exposure to morphine-associated context facilitated long-term potentiation in the vSUB-NAc glutamatergic pathway via GluN2B-containing receptor activation.

    PubMed

    Li, Yi-Jing; Ping, Xing-Jie; Qi, Chong; Shen, Fang; Sun, Lin-Lin; Sun, Xiao-Wei; Ge, Fei-Fei; Xing, Guo-Gang; Cui, Cai-Lian

    2017-03-01

    The glutamatergic projection from the ventral subiculum of the hippocampus (vSUB) to the nucleus accumbens (NAc) shell has been reported to play a key role in drug-related behavior. The GluN2B subunit of N-methyl-D-aspartate receptors (NMDARs) in the NAc can be selectively elevated after the retrieval of drug-conditioned memory. However, whether the increased GluN2B-containing NMDARs (GluN2B-NMDARs) are able to alter the synaptic plasticity of the vSUB-NAc glutamatergic pathway remains unclear. Here, we found that the long-term potentiation (LTP) in the vSUB-NAc pathway was facilitated and the GluN2B subunit protein level was elevated in synaptoneurosomes of the NAc shell, but not in the core, following morphine-induced conditioned place preference (CPP) expression in rats. The facilitated LTP was prevented by the GluN2B-NMDAR antagonist RO25-6981. Also, a neurochemical disconnection following microinjection of RO25-6981 into the NAc shell, plus microinfusion of GABA agonist baclofen and muscimol into the contralateral vSUB prevented the expression of morphine-induced CPP. These findings suggest that the retrieval of drug-associated memory potentiated synaptic plasticity in the vSUB-NAc pathway, which was dependent on GluN2B-NMDAR activation in the NAc shell. These findings provide a new explanation for the mechanisms that underlie the morphine-associated-context memory. The GluN2B-NMDARs may be regarded as a potential target for erasing morphine-related memory.

  10. Influenza vaccination coverage among medical residents: an Italian multicenter survey.

    PubMed

    Costantino, Claudio; Mazzucco, Walter; Azzolini, Elena; Baldini, Cesare; Bergomi, Margherita; Biafiore, Alessio Daniele; Bianco, Manuela; Borsari, Lucia; Cacciari, Paolo; Cadeddu, Chiara; Camia, Paola; Carluccio, Eugenia; Conti, Andrea; De Waure, Chiara; Di Gregori, Valentina; Fabiani, Leila; Fallico, Roberto; Filisetti, Barbara; Flacco, Maria E; Franco, Elisabetta; Furnari, Roberto; Galis, Veronica; Gallea, Maria R; Gallone, Maria F; Gallone, Serena; Gelatti, Umberto; Gilardi, Francesco; Giuliani, Anna R; Grillo, Orazio C; Lanati, Niccolò; Mascaretti, Silvia; Mattei, Antonella; Micò, Rocco; Morciano, Laura; Nante, Nicola; Napoli, Giuseppe; Nobile, Carmelo Giuseppe; Palladino, Raffaele; Parisi, Salvatore; Passaro, Maria; Pelissero, Gabriele; Quarto, Michele; Ricciardi, Walter; Romano, Gabriele; Rustico, Ennio; Saponari, Anita; Schioppa, Francesco S; Signorelli, Carlo; Siliquini, Roberta; Trabacchi, Valeria; Triassi, Maria; Varetta, Alessia; Ziglio, Andrea; Zoccali, Angela; Vitale, Francesco; Amodio, Emanuele

    2014-01-01

    Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

  11. Program Facilitates Distributed Computing

    NASA Technical Reports Server (NTRS)

    Hui, Joseph

    1993-01-01

    KNET computer program facilitates distribution of computing between UNIX-compatible local host computer and remote host computer, which may or may not be UNIX-compatible. Capable of automatic remote log-in. User communicates interactively with remote host computer. Data output from remote host computer directed to local screen, to local file, and/or to local process. Conversely, data input from keyboard, local file, or local process directed to remote host computer. Written in ANSI standard C language.

  12. Implementation of the exception from informed consent regulations in a large multicenter emergency clinical trials network: the RAMPART experience.

    PubMed

    Silbergleit, Robert; Biros, Michelle H; Harney, Deneil; Dickert, Neal; Baren, Jill

    2012-04-01

    Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks.

  13. Infliximab-induced autoantibodies: a multicenter study.

    PubMed

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  14. Prospective Multicenter International Surveillance of Azole Resistance in Aspergillus fumigatus

    PubMed Central

    Arendrup, M.C.; Warris, A.; Lagrou, K.; Pelloux, H.; Hauser, P.M.; Chryssanthou, E.; Mellado, E.; Kidd, S.E.; Tortorano, A.M.; Dannaoui, E.; Gaustad, P.; Baddley, J.W.; Uekötter, A.; Lass-Flörl, C.; Klimko, N.; Moore, C.B.; Denning, D.W.; Pasqualotto, A.C.; Kibbler, C.; Arikan-Akdagli, S.; Andes, D.; Meletiadis, J.; Naumiuk, L.; Nucci, M.; Melchers, W.J.G.; Verweij, P.E.

    2015-01-01

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. PMID:25988348

  15. Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

    PubMed

    Naslund, Thomas C; Becker, Stacey Y

    2003-01-01

    Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success.

  16. Multicenter Quality Control of Hepatitis C Virus Protease Inhibitor Resistance Genotyping

    PubMed Central

    Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-01-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents. PMID:23426922

  17. Multicenter quality control of hepatitis C virus protease inhibitor resistance genotyping.

    PubMed

    Vallet, Sophie; Larrat, Sylvie; Laperche, Syria; Le Guillou-Guillemette, Hélène; Legrand-Abravanel, Florence; Bouchardeau, Françoise; Pivert, Adeline; Henquell, Cécile; Mirand, Audrey; André-Garnier, Elisabeth; Giordanengo, Valérie; Lagathu, Gisèle; Thibault, Vincent; Scholtes, Caroline; Schvoerer, Evelyne; Gaudy-Graffin, Catherine; Maylin, Sarah; Trimoulet, Pascale; Brochot, Etienne; Hantz, Sébastien; Gozlan, Joël; Roque-Afonso, Anne-Marie; Soussan, Patrick; Plantier, Jean-Christophe; Charpentier, Charlotte; Chevaliez, Stéphane; Colson, Philippe; Mackiewicz, Vincent; Aguilera, Lina; Rosec, Sylvain; Gouriou, Stéphanie; Magnat, Nelly; Lunel-Fabiani, Françoise; Izopet, Jacques; Morand, Patrice; Payan, Christopher; Pawlotsky, Jean-Michel

    2013-05-01

    Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.

  18. Remission of rheumatoid arthritis and potential determinants: a national multi-center cross-sectional survey.

    PubMed

    Wang, Guan-Ying; Zhang, Sa-Li; Wang, Xiu-Ru; Feng, Min; Li, Chun; An, Yuan; Li, Xiao-Feng; Wang, Li-Zhi; Wang, Cai-Hong; Wang, Yong-Fu; Yang, Rong; Yan, Hui-Ming; Wang, Guo-Chun; Lu, Xin; Liu, Xia; Zhu, Ping; Chen, Li-Na; Jin, Hong-Tao; Liu, Jin-Ting; Guo, Hui-Fang; Chen, Hai-Ying; Xie, Jian-Li; Wei, Ping; Wang, Jun-Xiang; Liu, Xiang-Yuan; Sun, Lin; Cui, Liu-Fu; Shu, Rong; Liu, Bai-Lu; Yu, Ping; Zhang, Zhuo-Li; Li, Guang-Tao; Li, Zhen-Bin; Yang, Jing; Li, Jun-Fang; Jia, Bin; Zhang, Feng-Xiao; Tao, Jie-Mei; Lin, Jin-Ying; Wei, Mei-Qiu; Liu, Xiao-Min; Ke, Dan; Hu, Shao-Xian; Ye, Cong; Han, Shu-Ling; Yang, Xiu-Yan; Li, Hao; Huang, Ci-Bo; Gao, Ming; Lai, Bei; Cheng, Yong-Jing; Li, Xing-Fu; Song, Li-Jun; Yu, Xiao-Xia; Wang, Ai-Xue; Wu, Li-Jun; Wang, Yan-Hua; He, Lan; Sun, Wen-Wen; Gong, Lu; Wang, Xiao-Yuan; Wang, Yi; Zhao, Yi; Li, Xiao-Xia; Wang, Yan; Zhang, Yan; Su, Yin; Zhang, Chun-Fang; Mu, Rong; Li, Zhan-Guo

    2015-02-01

    The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.

  19. Tree-structured survival analysis of patients with Pseudomonas aeruginosa bacteremia: A multicenter observational cohort study.

    PubMed

    Yoon, Young Kyung; Kim, Hyun Ah; Ryu, Seong Yeol; Lee, Eun Jung; Lee, Mi Suk; Kim, Jieun; Park, Seong Yeon; Yang, Kyung Sook; Kim, Shin Woo

    2017-02-01

    This study aimed to construct a prediction algorithm, which is readily applicable in the clinical setting, to determine the mortality rate for patients with P. aeruginosa bacteremia. A multicenter observational cohort study was performed retrospectively in seven university-affiliated hospitals in Korea from March 2012 to February 2015. In total, 264 adult patients with monomicrobial P. aeruginosa bacteremia were included in the analyses. Among the predictors independently associated with 30-day mortality in the Cox regression model, Pitt bacteremia score >2 and high-risk source of bacteremia were identified as critical nodes in the tree-structured survival analysis. Particularly, the empirical combination therapy was not associated with any survival benefit in the Cox regression model compared to the empirical monotherapy. This study suggests that determining the infection source and evaluating the clinical severity are critical to predict the clinical outcome in patients with P. aeruginosa bacteremia.

  20. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal.

  1. Multicenter patient records research: security policies and tools.

    PubMed

    Behlen, F M; Johnson, S B

    1999-01-01

    The expanding health information infrastructure offers the promise of new medical knowledge drawn from patient records. Such promise will never be fulfilled, however, unless researchers first address policy issues regarding the rights and interests of both the patients and the institutions who hold their records. In this article, the authors analyze the interests of patients and institutions in light of public policy and institutional needs. They conclude that the multicenter study, with Institutional Review Board approval of each study at each site, protects the interests of both. "Anonymity" is no panacea, since patient records are so rich in information that they can never be truly anonymous. Researchers must earn and respect the trust of the public, as responsible stewards of facts about patients' lives. The authors find that computer security tools are needed to administer multicenter patient records studies and describe simple approaches that can be implemented using commercial database products.

  2. Multi-Center Traffic Management Advisor Operational Field Test Results

    NASA Technical Reports Server (NTRS)

    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.

  3. Prospective Multicenter Study of Children With Bronchiolitis Requiring Mechanical Ventilation

    PubMed Central

    Piedra, Pedro A.; Stevenson, Michelle D.; Sullivan, Ashley F.; Forgey, Tate F.; Clark, Sunday; Espinola, Janice A.; Camargo, Carlos A.

    2012-01-01

    OBJECTIVE: To identify factors associated with continuous positive airway pressure (CPAP) and/or intubation for children with bronchiolitis. METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with bronchiolitis. For 3 consecutive years from November 1 until March 31, beginning in 2007, researchers collected clinical data and a nasopharyngeal aspirate from study participants. We oversampled children from the ICU. Samples of nasopharyngeal aspirate were tested by polymerase chain reaction for 18 pathogens. RESULTS: There were 161 children who required CPAP and/or intubation. The median age of the overall cohort was 4 months; 59% were male; 61% white, 24% black, and 36% Hispanic. In the multivariable model predicting CPAP/intubation, the significant factors were: age <2 months (odds ratio [OR] 4.3; 95% confidence interval [CI] 1.7–11.5), maternal smoking during pregnancy (OR 1.4; 95% CI 1.1–1.9), birth weight <5 pounds (OR 1.7; 95% CI 1.0–2.6), breathing difficulty began <1 day before admission (OR 1.6; 95% CI 1.2–2.1), presence of apnea (OR 4.8; 95% CI 2.5–8.5), inadequate oral intake (OR 2.5; 95% CI 1.3–4.3), severe retractions (OR 11.1; 95% CI 2.4–33.0), and room air oxygen saturation <85% (OR 3.3; 95% CI 2.0–4.8). The optimism-corrected c-statistic for the final model was 0.80. CONCLUSIONS: In this multicenter study of children hospitalized with bronchiolitis, we identified several demographic, historical, and clinical factors that predicted the use of CPAP and/or intubation, including children born to mothers who smoked during pregnancy. We also identified a novel subgroup of children who required mechanical respiratory support <1 day after respiratory symptoms began. PMID:22869823

  4. The pediatric heart network: meeting the challenges to multicenter studies in pediatric heart disease

    PubMed Central

    Burns, Kristin M.; Pemberton, Victoria L.; Pearson, Gail D.

    2017-01-01

    Purpose of review Because of the relatively small numbers of pediatric patients with congenital heart disease cared for in any individual center, there is a significant need for multicenter clinical studies to validate new medical or surgical therapies. The Pediatric Heart Network (PHN), with 15 years of experience in multicenter clinical research, has tackled numerous challenges when conducting multicenter studies. Recent findings This review describes the challenges encountered and the strategies employed to conduct high-quality, collaborative research in pediatric cardiovascular disease. Summary Sharing lessons learned from the PHN can provide guidance to investigators interested in conducting pediatric multicenter studies. PMID:26196261

  5. Task Integration Facilitates Multitasking

    PubMed Central

    de Oliveira, Rita F.; Raab, Markus; Hegele, Mathias; Schorer, Jörg

    2017-01-01

    The aim of this study was to investigate multi-task integration in a continuous tracking task. We were particularly interested in how manipulating task structure in a dual-task situation affects learning of a constant segment embedded in a pursuit-tracking task. Importantly, we examined if dual-task effects could be attributed to task integration by varying the structural similarity and difficulty of the primary and secondary tasks. In Experiment 1 participants performed a pursuit tracking task while counting high-pitched tones and ignoring low-pitched tones. The tones were either presented randomly or structurally 250 ms before each tracking turn. Experiment 2 increased the motor load of the secondary tasks by asking participants to tap their feet to the tones. Experiment 3 further increased motor load of the primary task by increasing its speed and having participants tracking with their non-dominant hand. The results show that dual-task interference can be moderated by secondary task conditions that match the structure of the primary task. Therefore our results support proposals of task integration in continuous tracking paradigms. We conclude that multi-tasking is not always detrimental for motor learning but can be facilitated through task-integration. PMID:28360878

  6. Task Integration Facilitates Multitasking.

    PubMed

    de Oliveira, Rita F; Raab, Markus; Hegele, Mathias; Schorer, Jörg

    2017-01-01

    The aim of this study was to investigate multi-task integration in a continuous tracking task. We were particularly interested in how manipulating task structure in a dual-task situation affects learning of a constant segment embedded in a pursuit-tracking task. Importantly, we examined if dual-task effects could be attributed to task integration by varying the structural similarity and difficulty of the primary and secondary tasks. In Experiment 1 participants performed a pursuit tracking task while counting high-pitched tones and ignoring low-pitched tones. The tones were either presented randomly or structurally 250 ms before each tracking turn. Experiment 2 increased the motor load of the secondary tasks by asking participants to tap their feet to the tones. Experiment 3 further increased motor load of the primary task by increasing its speed and having participants tracking with their non-dominant hand. The results show that dual-task interference can be moderated by secondary task conditions that match the structure of the primary task. Therefore our results support proposals of task integration in continuous tracking paradigms. We conclude that multi-tasking is not always detrimental for motor learning but can be facilitated through task-integration.

  7. Program Facilitates CMMI Appraisals

    NASA Technical Reports Server (NTRS)

    Sweetser, Wesley

    2005-01-01

    A computer program has been written to facilitate appraisals according to the methodology of Capability Maturity Model Integration (CMMI). [CMMI is a government/industry standard, maintained by the Software Engineering Institute at Carnegie Mellon University, for objectively assessing the engineering capability and maturity of an organization (especially, an organization that produces software)]. The program assists in preparation for a CMMI appraisal by providing drop-down lists suggesting required artifacts or evidence. It identifies process areas for which similar evidence is required and includes a copy feature that reduces or eliminates repetitive data entry. It generates reports to show the entire framework for reference, the appraisal artifacts to determine readiness for an appraisal, and lists of interviewees and questions to ask them during the appraisal. During an appraisal, the program provides screens for entering observations and ratings, and reviewing evidence provided thus far. Findings concerning strengths and weaknesses can be exported for use in a report or a graphical presentation. The program generates a chart showing capability level ratings of the organization. A context-sensitive Windows help system enables a novice to use the program and learn about the CMMI appraisal process.

  8. CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells

    PubMed Central

    Selb, Regina; Eckl-Dorna, Julia; Neunkirchner, Alina; Schmetterer, Klaus; Marth, Katharina; Gamper, Jutta; Jahn-Schmid, Beatrice; Pickl, Winfried F.; Valenta, Rudolf; Niederberger, Verena

    2017-01-01

    Background Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. Objective We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Methods Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. Results In allergic patients the vast majority of CD23 molecules were expressed on naive IgD+ B cells. The density of CD23 molecules on B cells but not the number of CD23+ cells correlated with total IgE levels (RS = 0.53, P = .03) and allergen-induced skin reactions (RS = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. Conclusion CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells. PMID:27372566

  9. Oligonucleotide facilitators may inhibit or activate a hammerhead ribozyme.

    PubMed Central

    Jankowsky, E; Schwenzer, B

    1996-01-01

    Facilitators are oligonucleotides capable of affecting hammerhead ribozyme activity by interacting with the substrate at the termini of the ribozyme. Facilitator effects were determined in vitro using a system consisting of a ribozyme with 7 nucleotides in every stem sequence and two substrates with inverted facilitator binding sequences. The effects of 9mer and 12mer RNA as well as DNA facilitators which bind either adjacent to the 3'- or 5'-end of the ribozyme were investigated. A kinetic model was developed which allows determination of the apparent dissociation constant of the ribozyme-substrate complex from single turnover reactions. We observed a decreased dissociation constant of the ribozyme-substrate complex due to facilitator addition corresponding to an additional stabilization energy of delta delta G=-1.7 kcal/mol with 3'-end facilitators. The cleavage rate constant was increased by 3'-end facilitators and decreased by 5'-end facilitators. Values for Km were slightly lowered by all facilitators and kcat was increased by 3'-end facilitators and decreased by 5'-end facilitators in our system. Generally the facilitator effects increased with the length of the facilitators and RNA provided greater effects than DNA of the same sequence. Results suggest facilitator influences on several steps of the hammerhead reaction, substrate association, cleavage and dissociation of products. Moreover, these effects are dependent in different manners on ribozyme and substrate concentration. This leads to the conclusion that there is a concentration dependence whether activation or inhibition is caused by facilitators. Conclusions are drawn with regard to the design of hammerhead ribozyme facilitator systems. PMID:8602353

  10. GWATCH: a web platform for automated gene association discovery analysis

    PubMed Central

    2014-01-01

    Background As genome-wide sequence analyses for complex human disease determinants are expanding, it is increasingly necessary to develop strategies to promote discovery and validation of potential disease-gene associations. Findings Here we present a dynamic web-based platform – GWATCH – that automates and facilitates four steps in genetic epidemiological discovery: 1) Rapid gene association search and discovery analysis of large genome-wide datasets; 2) Expanded visual display of gene associations for genome-wide variants (SNPs, indels, CNVs), including Manhattan plots, 2D and 3D snapshots of any gene region, and a dynamic genome browser illustrating gene association chromosomal regions; 3) Real-time validation/replication of candidate or putative genes suggested from other sources, limiting Bonferroni genome-wide association study (GWAS) penalties; 4) Open data release and sharing by eliminating privacy constraints (The National Human Genome Research Institute (NHGRI) Institutional Review Board (IRB), informed consent, The Health Insurance Portability and Accountability Act (HIPAA) of 1996 etc.) on unabridged results, which allows for open access comparative and meta-analysis. Conclusions GWATCH is suitable for both GWAS and whole genome sequence association datasets. We illustrate the utility of GWATCH with three large genome-wide association studies for HIV-AIDS resistance genes screened in large multicenter cohorts; however, association datasets from any study can be uploaded and analyzed by GWATCH. PMID:25374661

  11. Early and Late Retrieval of the ALN Removable Vena Cava Filter: Results from a Multicenter Study

    SciTech Connect

    Pellerin, O.; Barral, F. G.; Lions, C.; Novelli, L.; Beregi, J. P.; Sapoval, M.

    2008-09-15

    Retrieval of removable inferior vena cava (IVC) filters in selected patients is widely practiced. The purpose of this multicenter study was to evaluate the feasibility and results of percutaneous removal of the ALN removable filter in a large patient cohort. Between November 2003 and June 2006, 123 consecutive patients were referred for percutaneous extraction of the ALN filter at three centers. The ALN filter is a removable filter that can be implanted through a femoral/jugular vein approach and extracted by the jugular vein approach. Filter removal was attempted after an implantation period of 93 {+-} 15 days (range, 6-722 days) through the right internal jugular vein approach using the dedicated extraction kit after control inferior vena cavography. Following filter removal, vena cavograms were obtained in all patients. Successful extraction was achieved in all but one case. Among these successful retrievals, additional manipulation using a femoral approach was needed when the apex of the filter was close to the IVC wall in two patients. No immediate IVC complications were observed according to the postimplantation cavography. Neither technical nor clinical differences between early and late filter retrieval were noticed. Our data confirm the safety of ALN filter retrieval up to 722 days after implantation. In infrequent cases, additional endovenous filter manipulation is needed to facilitate extraction.

  12. Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on Synchron LX-20 assays.

    PubMed

    Steen, Gerard; Vermeer, Henricus J; Naus, André J M; Goevaerts, Berrie; Agricola, Pauline T; Schoenmakers, Christian H H

    2006-01-01

    The influence of interference by hemolysis, icterus and lipemia on the results of routine chemistries may lead to wrong interpretations. The H-, I- and L-indices that can be measured by the Beckman LX-20 instrument (Beckman Coulter) in serum or plasma samples are a reliable semi-quantitative measure of the size of these interferences. A survey carried out in 16 Dutch clinical laboratories on the use of these indices demonstrated that in several of these laboratories, the influence of interferences is largely underestimated. Therefore, a multicenter study was carried out in which we examined the interference of hemolysis, icterus and lipemia on 32 analytes. On the basis of biological variation, we decided on cutoff indices above which analytically significant interference exists. We found analytically significant interference by hemolysis, icterus or lipemia, in 12, 7 and 15 of the 32 analytes studied, respectively. Flagging of results on the basis of analytically significant interference, however, results in too many clinically insignificant comments. On the basis of clinical significance, we conclude that significant interference by hemolysis, icterus or lipemia is present in only 5, 6 and 12 of the analytes studied, respectively. Use of the cutoff indices presented here facilitates optimal use of the LX-20 indices to prevent reporting of wrong results due to interference.

  13. Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

    PubMed

    Starling, R C; Stehlik, J; Baran, D A; Armstrong, B; Stone, J R; Ikle, D; Morrison, Y; Bridges, N D; Putheti, P; Strom, T B; Bhasin, M; Guleria, I; Chandraker, A; Sayegh, M; Daly, K P; Briscoe, D M; Heeger, P S

    2016-01-01

    Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

  14. Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development.

    PubMed

    David, Laurence S; Garcia, Esperanza; Cain, Stuart M; Thau, Elana; Tyson, John R; Snutch, Terrance P

    2010-01-01

    Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (Ca(V)3.1, Ca(V)3.2,Ca(V)3.3), although it remains to be described whether specific splice variants are associated with developmental states and pathological conditions. We aimed to identify and functionally characterize Ca(V)3.2 T-type Ca channel alternatively spliced variants from newborn animals and to compare with adult normotensive and spontaneously hypertensive rats (SHR). DNA sequence analysis of full-length Ca(V)3.2 cDNA generated from newborn heart tissue identified ten major regions of alternative splicing, the more common variants of which were analyzed by quantitative real-time PCR (qRT-PCR) and also subject to functional examination by whole-cell patch clamp. The main findings are that: (1) cardiac Ca(V)3.2 T-type Ca channels are subject to considerable alternative splicing, (2) there is preferential expression of Ca(V)3.2(-25) splice variant channels in newborn rat heart with a developmental shift in adult heart that results in approximately equal levels of expression of both (+25) and (-25) exon variants, (3) in the adult stage of hypertensive rats there is a both an increase in overall Ca(V)3.2 expression and a shift towards expression of Ca(V)3.2(+25) containing channels as the predominant form, and (4) alternative splicing confers a variant-specific voltage-dependent facilitation of Ca(V)3.2 channels. We conclude that Ca(V)3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states.

  15. Facilitating Dialogues about Racial Realities

    ERIC Educational Resources Information Center

    Quaye, Stephen John

    2014-01-01

    Background/Context: Facilitating dialogues about racial issues in higher education classroom settings continues to be a vexing problem facing postsecondary educators. In order for students to discuss race with their peers, they need skilled facilitators who are knowledgeable about racial issues and able to support students in these difficult…

  16. Facilitated Communication in Mainstream Schools.

    ERIC Educational Resources Information Center

    Remington-Gurney, Jane; Crossley, Rosemary

    Facilitated communication is described as a method of training communication partners or facilitators to provide physical assistance to communication aid users, to help them overcome physical and emotional problems in using their aids. In Melbourne (Victoria, Australia), the DEAL (Dignity, Education and Language) Centre has identified 96 people…

  17. A Manual for Group Facilitators.

    ERIC Educational Resources Information Center

    Auvine, Brian; And Others

    This resource manual presents guidelines and effective techniques for people who want to acquire group facilitation skills. It is a valuable resource for anyone planning or presenting a workshop; trainers or teachers interested in innovative classroom techniques; and anyone involved in a group as leader, facilitator, or participant. The manual…

  18. Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

    PubMed Central

    Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

    2015-01-01

    Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

  19. Retrospective Multicenter Study on Risk Factors for Surgical Site Infections after Appendectomy for Acute Appendicitis

    PubMed Central

    Giesen, Louis J.X.; van den Boom, Anne Loes; van Rossem, Charles C.; den Hoed, P.T.; Wijnhoven, Bas P.L.

    2016-01-01

    Background Surgical site infections (SSI) are seen in up to 5% of patients after appendectomy for acute appendicitis. SSI are associated with prolonged hospital stay and increased costs. The aim of this multicenter study was to identify factors associated with SSI after appendectomy for acute appendicitis. Methods Patients who underwent appendectomy for acute appendicitis between June 2014 and January 2015 in 6 teaching hospitals in the southwest of the Netherlands were included. Patient, diagnostic, intra-operative and disease-related factors were collected from the patients' charts. Primary outcome was surgical site infection. Multivariable logistic regression was performed to identify independent risk factors for SSI. Results Some 637 patients were included. Forty-two patients developed a SSI. In univariable analysis body temperature >38°C, CRP>65 and complex appendicitis were associated with SSI. After multivariable logistic regression with stepwise backwards elimination, complex appendicitis was significantly associated with SSI (OR 4.09; 95% CI 2.04-8.20). Appendiceal stump closure with a stapler device was inversely correlated with SSI (OR 0.40; 95% CI 0.24-0.97) Conclusions Complex appendicitis is a risk factor for SSI and warrants close monitoring postoperatively. The use of a stapler device for appendiceal stump closure is associated with a reduced risk of SSI. PMID:27631081

  20. Supporting Online AP Students: The Rural Facilitator and Considerations for Training

    ERIC Educational Resources Information Center

    Hendrix, Nicole; Degner, Katherine

    2016-01-01

    Online courses supplemented by on-site facilitators help many rural students pursue advanced coursework, but research is warranted to better understand facilitator role and training needs. This study examined facilitation experiences, demographic characteristics, and professional development activities of rural on-site facilitators associated with…

  1. Reappraisal of known malaria resistance loci in a large multicenter study.

    PubMed

    2014-11-01

    Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. There was evidence of association at P < 1 × 10(-4) with the HBB, ABO, ATP2B4, G6PD and CD40LG loci, but previously reported associations at 22 other loci did not replicate in the multicenter analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, with a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed.

  2. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): The study methodology, recruitment, and baseline demographic and disease characteristics

    PubMed Central

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R.; Andrews, Leslie; Rabkin, Judith G.; McElhiney, Martin; Nieves, Jeri; Santella, Regina M.; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S.; Miller, Robert G; Katz, Jonathan S.; Forshew, Dallas; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Bjorn; Filho, J Americo M. Fernandes; Kasarskis, Edward J.; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Shefner, Jeremy M.; Andrews, Jinsy A.; Koczon-Jaremko, Boguslawa A.

    2015-01-01

    Objective In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods An extensive structured telephone interview ascertained environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3 to 6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Results 355 patients were recruited. Subjects were enrolled over a 36 month-period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, with the only difference being type of health insurance among enrolled patients. Sites were divided into 3 groups by the number of enrolled subjects. Comparing these 3 groups, the Columbia site had fewer “definite ALS” diagnoses. Conclusion This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and was accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized. PMID:24564738

  3. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): study methodology, recruitment, and baseline demographic and disease characteristics.

    PubMed

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R; Andrews, Leslie; Rabkin, Judith G; McElhiney, Martin; Nieves, Jeri; Santella, Regina M; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S; Miller, Robert G; Katz, Jonathan S; Forshew, Dallas; Barohn, Richard J; Sorenson, Eric J; Oskarsson, Bjorn; Fernandes Filho, J Americo M; Kasarskis, Edward J; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D; Nations, Sharon P; Swenson, Andrea J; Shefner, Jeremy M; Andrews, Jinsy A; Koczon-Jaremko, Boguslawa A

    2014-06-01

    Abstract In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods utilize an extensive structured telephone interview ascertaining environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3-6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Three hundred and fifty-five patients were recruited. Subjects were enrolled over a 36-month period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Results showed that demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, the only difference being type of health insurance among enrolled patients. Sites were divided into three groups by the number of enrolled subjects. Comparing these three groups, the Columbia site had fewer 'definite ALS' diagnoses. This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and has been accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized.

  4. [Multicenter trial for sudden hearing loss therapy - planning and concept].

    PubMed

    Plontke, S K; Girndt, M; Meisner, C; Probst, R; Oerlecke, I; Richter, M; Steighardt, J; Dreier, G; Weber, A; Baumann, I; Plößl, S; Löhler, J; Laszig, R; Werner, J A; Rahne, T

    2016-04-01

    Systemic steroids are widely used worldwide as a standard of care for primary therapy of idiopathic sudden sensorineural hearing loss (ISSHL). The German ISSHL guideline recommends high-dose steroids for primary therapy of ISSHL, without evidence from randomized controlled trials (RCTs). The rationale for the treatment of ISSHL using high dose steroids is only based on retrospective cohort studies.This article describes the planning and initiation of a multicenter, national, randomized, controlled clinical trial entitled Efficacy and safety of high dose glucocorticosteroid treatment for idiopathic sudden sensorineural hearing loss - a three-armed, randomized, triple-blind, multicenter trial (HODOKORT). This clinical trial aims to compare standard dose with two types of high-dose steroids for primary systemic therapy with respect to their efficacy in improving hearing, and thus communication ability, in patients with idiopathic sudden sensorineural hearing loss.This study is funded by the "Clinical Trials with High Patient Relevance" research program in the health research framework of the German Federal Ministry of Education and Research. It is one of two studies by the German Study Center of Clinical Trials of the German Society of Otorhinolaryngology, Head and Neck Surgery (DSZ-HNO). Planning and initiation was done in cooperation with the DSZ-HNO, the Coordination Center of Clinical Trials of the Martin-Luther-University Halle-Wittenberg, and the Study Center of the University Hospital Freiburg.

  5. Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

    PubMed Central

    Ugurluer, Gamze; Miller, Robert C.; Li, Yexiong; Thariat, Juliette; Ghadjar, Pirus; Schick, Ulrike; Ozsahin, Mahmut

    2016-01-01

    Primary hepatic lymphoma (PHL) is a rare malignancy. We aimed to assess the clinical profile, outcome and prognostic factors in PHL through the Rare Cancer Network (RCN). A retrospective analysis of 41 patients was performed. Median age was 62 years (range, 23-86 years) with a male-to-female ratio of 1.9:1.0. Abdominal pain or discomfort was the most common presenting symptom. Regarding B-symptoms, 19.5% of patients had fever, 17.1% weight loss, and 9.8% night sweats. The most common radiological presentation was multiple lesions. Liver function tests were elevated in 56.1% of patients. The most common histopathological diagnosis was diffuse large B-cell lymphoma (65.9%). Most of the patients received Chop-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens; 4 patients received radiotherapy (dose range, 30.6-40.0 Gy). Median survival was 163 months, and 5- and 10-year overall survival rates were 77 and 59%, respectively. The 5- and 10-year disease-free and lymphoma-specific survival rates were 69, 56, 87 and 70%, respectively. Multivariate analysis revealed that fever, weight loss, and normal hemoglobin level were the independent factors influencing the outcome. In this retrospective multicenter RCN study, patients with PHL had a relatively better prognosis than that reported elsewhere. Multicenter prospective studies are still warranted to establish treatment guidelines, outcome, and prognostic factors. PMID:27746888

  6. MAIN ETHICAL BREACHES IN MULTICENTER CLINICAL TRIALS REGULATIONS OF TURKEY

    PubMed Central

    Ekmekci, P. Elif

    2017-01-01

    Turkey has been a growing market for multicenter clinical trials for the last ten years and is considered among the top ten countries in terms of potential study subject populations. The objective of increasing the share of Turkey in multicenter clinical trials is strongly supported. This ambitious goal of Turkey raises the need to have regulations in compliance with other leading countries conducting clinical trials. The latest published Turkish regulations on clinical trials are structured in compliance with the International Conference on Harmonization (ICH) Guidelines and in harmony with the regulations of other leading countries in clinical research, such as the US. There are still flaws in Turkish regulation with the risk of violating human subjects’ rights and issues with responsible conduct of research. The aim of this article is to compare Turkish clinical trials regulations with those of the US, to determine if there exists any incompatibility between the countries’ regulations and, if so, how to ameliorate these. The main flaws in Turkish clinical trials regulations are identified as follows: lack of definition of the term “human subject; absence of explicit referral to the unacceptability of Conflict of Interest (COI) and taking measures to avoid it; exiguity of emphasis on plurality of the IRB members; nonexistence of a clear expression that this is research; and clinical equipoise, regarding the treatment of the existing clinical problem and lack of integration with international accreditation systems for Institutional Review Boards.

  7. Research and operational applications in multi-center ensemble forecasting

    NASA Astrophysics Data System (ADS)

    Zhu, Y.; Toth, Z.

    2009-05-01

    The North American Ensemble Forecast System (NAEFS) was built up in 2004 by the Meteorological Service of Canada (MSC), the National Meteorological Service of Mexico (NMSM), and the US National Weather Service (NWS) as an operational multi-center ensemble forecast system. Currently it combines the 20-member MSC and NWS ensembles to form a joint ensemble of 40 members twice a day. The joint ensemble forecast, after bias correction and statistical downscaling, is used to generate a suite of products for CONUS, North America and for other regions of the globe. The THORPEX Interactive Grand Global Ensemble (TIGGE) project has been established a few years ago to collect operational global ensemble forecasts from world centers, and distribute to the scientific community, to encourage research leading to the acceleration of improvements in the skill and utility of high impact weather forecasts. TIGGE research is expected to advise the development of the operational NAEFS system and eventually the two projects are expected to converge into a single operational system, the Global Interactive Forecast System (GIFS). This presentation will review recent developments, the current status, and plans related to the TIGGE research and NAEFS operational multi-center ensemble projects.

  8. Computational method for general multicenter electronic structure calculations.

    PubMed

    Batcho, P F

    2000-06-01

    Here a three-dimensional fully numerical (i.e., chemical basis-set free) method [P. F. Batcho, Phys. Rev. A 57, 6 (1998)], is formulated and applied to the calculation of the electronic structure of general multicenter Hamiltonian systems. The numerical method is presented and applied to the solution of Schrödinger-type operators, where a given number of nuclei point singularities is present in the potential field. The numerical method combines the rapid "exponential" convergence rates of modern spectral methods with the multiresolution flexibility of finite element methods, and can be viewed as an extension of the spectral element method. The approximation of cusps in the wave function and the formulation of multicenter nuclei singularities are efficiently dealt with by the combination of a coordinate transformation and a piecewise variational spectral approximation. The complete system can be efficiently inverted by established iterative methods for elliptical partial differential equations; an application of the method is presented for atomic, diatomic, and triatomic systems, and comparisons are made to the literature when possible. In particular, local density approximations are studied within the context of Kohn-Sham density functional theory, and are presented for selected subsets of atomic and diatomic molecules as well as the ozone molecule.

  9. Multicenter Case-Control Study on Restless Legs Syndrome in Multiple Sclerosis: the REMS Study

    PubMed Central

    Manconi, Mauro; Ferini-Strambi, Luigi; Filippi, Massimo; Bonanni, Enrica; Iudice, Alfonso; Murri, Luigi; Gigli, Gian Luigi; Fratticci, Lara; Merlino, Giovanni; Terzano, Giovanni; Granella, Franco; Parrino, Liborio; Silvestri, Rosalia; Aricò, Irene; Dattola, Vincenzo; Russo, Giovanna; Luongo, Carmela; Cicolin, Alessandro; Tribolo, Antonella; Cavalla, Paola; Savarese, Mariantonietta; Trojano, Maria; Ottaviano, Salvatore; Cirignotta, Fabio; Simioni, Valentina; Salvi, Fabrizio; Mondino, Fiorella; Perla, Franco; Chinaglia, Giorgia; Zuliani, Cristina; Cesnik, Edward; Granieri, Enrico; Placidi, Fabio; Palmieri, Maria Giuseppina; Manni, Raffaele; Terzaghi, Michele; Bergamaschi, Roberto; Rocchi, Raffaele; Ulivelli, Monica; Bartalini, Sabina; Ferri, Raffaele; Fermo, Salvatore Lo; Ubiali, Emilio; Viscardi, Massimo; Rottoli, Mariarosa; Nobili, Lino; Protti, Alessandra; Ferrillo, Franco; Allena, Marta; Mancardi, Gianluigi; Guarnieri, Biancamaria; Londrillo, Francesco

    2008-01-01

    Study objectives: To verify the existence of a symptomatic form of restless legs syndrome (RLS) secondary to multiple sclerosis (MS) and to identify possible associated risk factors. Design: Prospective, multicenter, case-control epidemiologic survey. Settings: Twenty sleep centers certified by the Italian Association of Sleep Medicine. Patients: Eight hundred and sixty-one patients affected by MS and 649 control subjects. Interventions: N/A. Measures and results: Data regarding demographic and clinical factors, presence and severity of RLS, the results of hematologic tests, and visual analysis of cerebrospinal magnetic resonance imaging studies were collected. The prevalence of RLS was 19% in MS and 4.2% in control subjects, with a risk to be affected by RLS of 5.4 (95%confidence interval: 3.56–8.26) times greater for patients with MS than for control subjects. In patients with MS, the following risk factors for RLS were significant: older age; longer MS duration; the primary progressive MS form; higher global, pyramidal, and sensory disability; and the presence of leg jerks before sleep onset. Patients with MS and RLS more often had sleep complaints and a higher intake of hypnotic medications than patients with MS without RLS. RLS associated with MS was more severe than that of control subjects. Conclusions: RLS is significantly associated with MS, especially in patients with severe pyramidal and sensory disability. These results strengthen the idea that the inflammatory damage correlated with MS may induce a secondary form of RLS. As it does in idiopathic cases, RLS has a significant impact on sleep quality in patients with MS; therefore, it should be always searched for, particularly in the presence of insomnia unresponsive to treatment with common hypnotic drugs. Citation: Manconi M; Ferini-Strambi L; Filippi M; Bonanni E; Iudice A; Murri L; Gigli GL; Fratticci L; Merlino G; Terzano G; Granella F; Parrino L; Silvestri R; Aricò I; Dattola V; Russo G; Luongo

  10. Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons: identification of the substances responsible for the pharmacological action.

    PubMed

    Kawahata, Ichiro; Yoshida, Masaaki; Sun, Wen; Nakajima, Akira; Lai, Yanxin; Osaka, Naoya; Matsuzaki, Kentaro; Yokosuka, Akihito; Mimaki, Yoshihiro; Naganuma, Akira; Tomioka, Yoshihisa; Yamakuni, Tohru

    2013-10-01

    cAMP/PKA/ERK/CREB signaling linked to CRE-mediated transcription is crucial for learning and memory. We originally found nobiletin as a natural compound that stimulates this intracellular signaling and exhibits anti-dementia action in animals. Citrus reticulata or C. unshiu peels are employed as "chinpi" and include a small amount of nobiletin. We here provide the first evidence for beneficial pharmacological actions on the cAMP/PKA/ERK/CREB cascade of extracts from nobiletin-rich C.reticulata peels designated as Nchinpi, the nobiletin content of which was 0.83 ± 0.13% of the dry weight or 16-fold higher than that of standard chinpi extracts. Nchinpi extracts potently facilitated CRE-mediated transcription in cultured hippocampal neurons, whereas the standard chinpi extracts showed no such activity. Also, the Nchinpi extract, but not the standard chinpi extract, stimulated PKA/ERK/CREB signaling. Interestingly, treatment with the Nchinpi extract at the concentration corresponding to approximately 5 μM nobiletin more potently facilitated CRE-mediated transcriptional activity than did 30 μM nobiletin alone. Consistently, sinensetin, tangeretin, 6-demethoxynobiletin, and 6-demethoxytangeretin were also identified as bioactive substances in Nchinpi that facilitated the CRE-mediated transcription. Purified sinensetin enhanced the transcription to a greater degree than nobiletin. Furthermore, samples reconstituted with the four purified compounds and nobiletin in the ratio of each constituent's content in the extract showed activity almost equal to that of the Nchinpi extract to stimulate CRE-mediated transcription. These findings suggest that above four compounds and nobiletin in the Nchinpi extract mainly cooperated to facilitate potently CRE-mediated transcription linked to the upstream cAMP/PKA/ERK/CREB pathway in hippocampal neurons.

  11. Prospective study of attitudinal and relationship predictors of sexual risk in the multicenter AIDS cohort study.

    PubMed

    Ostrow, David G; Silverberg, Michael J; Cook, Robert L; Chmiel, Joan S; Johnson, Lisette; Li, Xiuhong; Jacobson, Lisa P

    2008-01-01

    We examined the influence of attitudes concerning HIV transmission, safe sex, and sexual sensation seeking, as well as negotiated risk reduction with primary partners, on the proportion of unprotected sexual partners (%UASP) among men who have sex with men (MSM). Participants were 263 HIV-seropositive and 238 HIV-seronegative MSM in the Multicenter AIDS Cohort Study between 1999 and 2003 who completed a 20-item attitude survey twice. Behavioral data were collected concurrently and 6-12 months after each survey. Among seropositives, decreased HIV concern and increased safer sex fatigue were associated with higher %UASP at 6 and 12 months. Among seronegatives, increased %UASP at 12 months was associated with safer sex fatigue. At 6 months and 12 months, risk reduction agreements were associated with increased %UASP among seronegatives in seroconcordant monogamous relationships, reflecting their abandonment of condoms in such partnerships. We conclude that HIV prevention efforts should target modifiable attitudes (reduced concern about HIV and safer sex fatigue) and increases in sexual risk-taking of MSM, particularly among HIV+ men having sex with serodiscordant partners.

  12. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    PubMed Central

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  13. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    PubMed

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders.

  14. Hydrogen multicenter bond in oxide and nitride semiconductors

    NASA Astrophysics Data System (ADS)

    Janotti, Anderson

    2009-03-01

    Hydrogen is a very reactive atom, occurring in virtually all organic and in many inorganic compounds. It can form a purely covalent bond, in which two hydrogen atoms share a pair of electrons in a two-electron two-center bond, as well as polar covalent bonds, such as in an H2O molecule. In solids, hydrogen is usually considered as an interstitial impurity. In elemental semiconductors, such as silicon, hydrogen forms a three-center bond when located at the bond center. In compound semiconductors, hydrogen bonds to the anionic species in p-type material, and to the cationic species in n-type. Thus far, hydrogen in solids has been found to form chemical bonds with one, two, or at most three other atoms. Higher coordination numbers are exceedingly rare and have been reported only for clusters. In this talk we will show that hydrogen is capable of forming multicenter bonds in solids, occupying substitutional sites. As examples, we discuss substitutional hydrogen impurities in oxides (ZnO, MgO, SnO2, TiO2) [1,2] and nitrides (InN, AlN, GaN) [3]. Based on first-principles calculations we show that hydrogen replaces oxygen (nitrogen) and forms genuine chemical bonds with multiple metal atoms, in truly multicoordinated configurations. These multicenter bonds are surprisingly strong despite the large hydrogen-metal distances when compared to typical values in hydrogen two-center bonds. Hydrogen in the multicenter bond configuration is a shallow donor in a number of materials. In conducting oxides, it provides a consistent explanation for the observed dependence of electrical conductivity on oxygen partial pressure, thus resolving a long-standing controversy on the role of point defects in unintentional n-type conductivity [1,2]. [4pt] [1] A. Janotti and C. G Van de Walle, Nature Materials 6, 44 (2007). [0pt] [2] A. K. Singh, A. Janotti, M. Scheffler, and C. G. Van de Walle, Phys. Rev. Lett. 101, 055502 (2008). [0pt] [3] A. Janotti and C. G. Van de Walle, Appl. Phys. Lett. 92

  15. Singing can facilitate foreign language learning.

    PubMed

    Ludke, Karen M; Ferreira, Fernanda; Overy, Katie

    2014-01-01

    This study presents the first experimental evidence that singing can facilitate short-term paired-associate phrase learning in an unfamiliar language (Hungarian). Sixty adult participants were randomly assigned to one of three "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing. Participants in the singing condition showed superior overall performance on a collection of Hungarian language tests after a 15-min learning period, as compared with participants in the speaking and rhythmic speaking conditions. This superior performance was statistically significant (p < .05) for the two tests that required participants to recall and produce spoken Hungarian phrases. The differences in performance were not explained by potentially influencing factors such as age, gender, mood, phonological working memory ability, or musical ability and training. These results suggest that a "listen-and-sing" learning method can facilitate verbatim memory for spoken foreign language phrases.

  16. Facilitation of learning: part 1.

    PubMed

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-06

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning.

  17. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

    PubMed Central

    2014-01-01

    Introduction Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). Methods A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. Results A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. Conclusions Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients. PMID:25047960

  18. Factors predicting survival in ALS: a multicenter Italian study.

    PubMed

    Calvo, Andrea; Moglia, Cristina; Lunetta, Christian; Marinou, Kalliopi; Ticozzi, Nicola; Ferrante, Gianluca Drago; Scialo, Carlo; Sorarù, Gianni; Trojsi, Francesca; Conte, Amelia; Falzone, Yuri M; Tortelli, Rosanna; Russo, Massimo; Chiò, Adriano; Sansone, Valeria Ada; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Monsurrò, Maria Rosaria; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fini, Nicola; Mandrioli, Jessica

    2017-01-01

    The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected. The median survival time from onset to death/tracheostomy was 44 months (SE 1.18, CI 42-46). According to univariate analysis, factors related to survival from onset to death/tracheostomy were: age at onset, diagnostic delay, site of onset, phenotype, degree of certainty at diagnosis according to revised El Escorial criteria (R-EEC), presence/absence of dementia, BMI at diagnosis, patients' provenance. In the multivariate analysis, age at onset, diagnostic delay, phenotypes but not site of onset, presence/absence of dementia, BMI, riluzole use, R-EEC criteria were independent prognostic factors of survival in ALS. We compared patients from an ALS Registry with patients from tertiary centers; the latter ones were younger, less frequently bulbar, but more frequently familial and definite at diagnosis. Our large, multicenter study demonstrated the role of some clinical and demographic factors on ALS survival, and showed some interesting differences between referral centers' patients and the general ALS population. These results can be helpful for clinical practice, in clinical trial design and to validate new tools to predict disease progression.

  19. Factors influencing the quality of postoperative epidural analgesia: an observational multicenter study

    PubMed Central

    Wranicz, Piotr; Andersen, Hege; Nordbø, Arve; Kongsgaard, Ulf E

    2014-01-01

    Background Epidural analgesia (EDA) is used widely for postoperative pain treatment. However, studies have reported a failure rate of EDA of up to 30%. We aimed to evaluate the quality of postoperative EDA in patients undergoing a laparotomy in five Norwegian hospitals. Methods This was a multicenter observational study in patients undergoing a laparotomy with epidural-based postoperative analgesia. Data were registered at three time points. Technical aspects, infusion rates, pain intensity, assessment procedures, side effects, and satisfaction of patients and health personnel were recorded. The use of other pain medications and coanalgesics was registered. Results Three hundred and seventeen patients were included. Pain control at rest was satisfactory in 89% of patients at 24 hours and in 91% at 48 hours. Pain control when coughing was satisfactory in 62% at 24 hours and in 59% at 48 hours. The spread of hypoesthesia was consistent for each individual patient but varied between patients. The hypoesthetic area was not associated with pain intensity, and the precision of the EDA insertion point was not associated with the pain score. Few side effects were reported. EDA was regarded as effective and functioning well by 64% of health personnel. Conclusion EDA was an effective method for postoperative pain relief at rest but did not give sufficient pain relief during mobilization. The use of cold stimulation to assess the spread of EDA had limited value as a clinical indicator of the efficacy of postoperative pain control. Validated tools for the control of EDA quality are needed. PMID:25206312

  20. Repair or observe moderate ischemic mitral regurgitation during coronary artery bypass grafting? Prospective randomized multicenter data

    PubMed Central

    Gulack, Brian C.; Englum, Brian R.; Castleberry, Anthony W.; Daneshmand, Mani A.; Perrault, Louis P.

    2015-01-01

    Ischemic mitral regurgitation (MR) is a common occurrence following myocardial infarction and its presence is associated with poor outcomes. The optimal treatment of ischemic MR is a matter of debate, especially for patients with moderate MR severity. Some authors advocate for isolated coronary artery bypass grafting (CABG) for patients with moderate MR, maintaining that reverse ventricular remodeling will reduce MR grade and its associated mortality risk, while others argue that a concomitant mitral valve repair (MVR) or replacement is superior. The Cardiothoracic Surgical Trials Network (CTSN) recently published the 1-year results of the Surgical Treatment of Moderate Ischemic Mitral Regurgitation study, a multicenter, randomized, controlled trial investigating the impact of MVR in addition to CABG compared to CABG alone in the treatment of moderate ischemic MR. Here, we have reviewed previous observational and prospective studies investigating moderate ischemic MR treatment as well as the results of the current CTSN randomized trial. Furthermore, we have summarized the current state of the available evidence and preview potential new information that will become available with planned subgroup analyses and further follow-up of enrolled patients in the recently completed CTSN trial. PMID:26309829

  1. Rationale and design of the Multicenter Medication Reconciliation Quality Improvement Study (MARQUIS)

    PubMed Central

    2013-01-01

    Background Unresolved medication discrepancies during hospitalization can contribute to adverse drug events, resulting in patient harm. Discrepancies can be reduced by performing medication reconciliation; however, effective implementation of medication reconciliation has proven to be challenging. The goals of the Multi-Center Medication Reconciliation Quality Improvement Study (MARQUIS) are to operationalize best practices for inpatient medication reconciliation, test their effect on potentially harmful unintentional medication discrepancies, and understand barriers and facilitators of successful implementation. Methods Six U.S. hospitals are participating in this quality improvement mentored implementation study. Each hospital has collected baseline data on the primary outcome: the number of potentially harmful unintentional medication discrepancies per patient, as determined by a trained on-site pharmacist taking a “gold standard” medication history. With the guidance of their mentors, each site has also begun to implement one or more of 11 best practices to improve medication reconciliation. To understand the effect of the implemented interventions on hospital staff and culture, we are performing mixed methods program evaluation including surveys, interviews, and focus groups of front line staff and hospital leaders. Discussion At baseline the number of unintentional medication discrepancies in admission and discharge orders per patient varies by site from 2.35 to 4.67 (mean=3.35). Most discrepancies are due to history errors (mean 2.12 per patient) as opposed to reconciliation errors (mean 1.23 per patient). Potentially harmful medication discrepancies averages 0.45 per patient and varies by site from 0.13 to 0.82 per patient. We discuss several barriers to implementation encountered thus far. In the end, we anticipate that MARQUIS tools and lessons learned have the potential to decrease medication discrepancies and improve patient outcomes. Trial

  2. Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial

    PubMed Central

    De Stefano, Carla; Normand, Domitille; Jabre, Patricia; Azoulay, Elie; Kentish-Barnes, Nancy; Lapostolle, Frederic; Baubet, Thierry; Reuter, Paul-Georges; Javaud, Nicolas; Borron, Stephen W.; Vicaut, Eric; Adnet, Frederic

    2016-01-01

    Background The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. Methods and Findings In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members’ experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. Conclusions Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death. PMID:27253993

  3. Social Facilitation of Aiding Responses.

    ERIC Educational Resources Information Center

    Bartell, Patricia; And Others

    Research on individual's response to emergency situations in the presence of others has produced conflicting results. The bystander effect is the label applied to inaction or the unlikelihood of assistance with others present. The social facilitation effect occurs when the presence of others energizes response; strong habit responses are…

  4. Facilitating Creativity in Adult Learners

    ERIC Educational Resources Information Center

    Tsai, Kuan Chen

    2013-01-01

    Creativity in education research has received increasing attention, although the major focus of this research has been on children. Despite pleas by several adult educators for promoting creativity, very few studies have focused on adult learners, leaving to it to be explored what approaches are useful for adult educators to facilitate creativity…

  5. SUPERFUND GROUNDWATER ISSUE - FACILITATED TRANSPORT

    EPA Science Inventory

    The Regional Superfund Ground Water Forum is a group of ground-water scientists representing EPA's Regional Superfund Offices, organized to exchange up to date information related to ground-water remediation at Superfund sites. Facilitated transport is an issue identified by the ...

  6. Facilitating Conditions for School Motivation.

    ERIC Educational Resources Information Center

    Yeung, Alexander Seeshing; McInerney, Dennis M.

    Primary and high school students (277 in grades 5-6; 615 in grades 7-12) in the United States (47 percent boys) responded to 26 items of the Facilitating Conditions Questionnaire (FCQ). Results indicate 7 distinct FCQ factors: perceived value of schooling; affect toward schooling; peer positive academic climate (Peer Positive); encouragement from…

  7. Facilitation of Mourning During Childhood.

    ERIC Educational Resources Information Center

    Kliman, Gilbert; And Others

    This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

  8. The neural correlates of picture naming facilitated by auditory repetition

    PubMed Central

    2012-01-01

    Background Overt repetition of auditorily presented words can facilitate picture naming performance in both unimpaired speakers and individuals with word retrieval difficulties, but the underlying neurocognitive mechanisms and longevity of such effects remain unclear. This study used functional magnetic resonance imaging to examine whether different neurological mechanisms underlie short-term (within minutes) and long-term (within days) facilitation effects from an auditory repetition task in healthy older adults. Results The behavioral results showed that both short- and long-term facilitated items were named significantly faster than unfacilitated items, with short-term items significantly faster than long-term items. Neuroimaging analyses identified a repetition suppression effect for long-term facilitated items, relative to short-term facilitated and unfacilitated items, in regions known to be associated with both semantic and phonological processing. A repetition suppression effect was also observed for short-term facilitated items when compared to unfacilitated items in a region of the inferior temporal lobe linked to semantic processing and object recognition, and a repetition enhancement effect when compared to long-term facilitated items in a posterior superior temporal region associated with phonological processing. Conclusions These findings suggest that different neurocognitive mechanisms underlie short- and long-term facilitation of picture naming by an auditory repetition task, reflecting both phonological and semantic processing. More specifically, the brain areas engaged were consistent with the view that long-term facilitation may be driven by a strengthening of semantic-phonological connections. Short-term facilitation, however, appears to result in more efficient semantic processing and/or object recognition, possibly in conjunction with active recognition of the phonological form. PMID:22364354

  9. Facilitating Facilitators to Facilitate, in Problem or Enquiry Based Learning Sessions

    ERIC Educational Resources Information Center

    Coelho, Catherine

    2014-01-01

    Problem based learning (PBL) has been used in dental education over the past 20 years and uses a patient case scenario to stimulate learning in a small group setting, where a trained facilitator does not teach but guides the group to bring about deep contextualized learning, to be empathetic to each other and to encourage fair and equitable…

  10. Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B

    PubMed Central

    Rigatto, Maria Helena; Oliveira, Maura S.; Perdigão-Neto, Lauro V.; Levin, Anna S.; Carrilho, Claudia M.; Tanita, Marcos Toshiyuki; Tuon, Felipe F.; Cardoso, Douglas E.; Lopes, Natane T.

    2016-01-01

    Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for ≥48 h. A multicenter prospective cohort study was performed that included patients aged ≥18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 ± 1.3 and 2.4 ± 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P < 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48; P < 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations. PMID:26856846

  11. Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study

    PubMed Central

    Wynn, Julia; Aspelund, Gudrun; Zygmunt, Annette; Stolar, Charles JH.; Mychaliska, George; Butcher, Jennifer; Lim, Foong-Yen; Gratton, Teresa; Potoka, Douglas; Brennan, Kate; Azarow, Ken; Jackson, Barbara; Needelman, Howard; Crombleholme, Timothy; Zhang, Yuan; Duong, Jimmy; Arkovitz, Marc S.; Chung, Wendy K.; Farkouh, Christiana

    2013-01-01

    Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at two years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at two years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 +/− 15, 95 +/−16, and 95 +/− 11. Ten percent (5/47) scored more than two standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 +/−14, 94+/−16, 93 +/− 13, 97+/− 10, and 94 +/− 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At two years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at two years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays. PMID:24094947

  12. A multicenter study of major depressive disorder among emergency department patients in Latin-American countries.

    PubMed

    Castilla-Puentes, Ruby C; Secin, Ricardo; Grau, Arturo; Galeno, Roxanna; Feijo de Mello, Marcelo; Pena, Nuri; Sanchez-Russi, Carlos A

    2008-01-01

    This multicenter study estimated the prevalence of major depressive disorder (MDD) among emergency department patients in Latin America. To identify patients with MDD, we used a combination of DSM IV- criteria interview and a questionnaire screen including the center for Epidemiological Studies Depression Scale. We analyzed data from consecutive adult patients from hospitals in Argentina, Brazil, Chile, Colombia, and Mexico and described the demographic and health status differences between MDD and non-MDD patients. Prevalence of MDD ranges from 23.0 to 35.0%. The estimates are based on a total of 1,835 patients aged 18 years and over, with response rates of 83.0%. Compared to non-MDD patients, MDD patients were more likely to be middle-aged, female, smokers, of lower socioeconomic status, and to report a diagnosis of asthma or arthritis/rheumatism. Multivariate analysis identified a lower level of education, smoking, and self-reported anxiety, chronic fatigue, and back problems to be independently associated with MDD. Our data suggest that the prevalence of MDD is elevated among emergency department patients in Latin American countries. The integration of depression screening into routine emergency care merits serious consideration, especially if such screening can be linked to psychiatric treatment.

  13. Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

    PubMed Central

    Sen, H. Nida; Drye, Lea T.; Goldstein, Debra A.; Larson, Theresa A.; Merrill, Pauline T.; Pavan, Peter R.; Sheppard, John D.; Burke, Alyce; Srivastava, Sunil K.; Jabs, Douglas A.

    2013-01-01

    Purpose To assess the prevalence of hypotony in patients with severe forms of uveitis. Methods The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. Results Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01). Conclusions Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment. PMID:22409563

  14. Symptomatic retention of the patency capsule: a multicenter real life case series

    PubMed Central

    Kopylov, Uri; Nemeth, Artur; Cebrian, Alba; Wurm Johansson, Gabriele; Thorlacius, Henrik; Fernandez-Urien Sainz, Ignacio; Koulaouzidis, Anastasios; Eliakim, Rami; Toth, Ervin

    2016-01-01

    Background and aims: The patency capsule is designed to evaluate the patency of the small bowel before administration of small-bowel capsule endoscopy (SBCE) in patients at high risk of retention. The utilization of a patency capsule may be associated with a risk of symptomatic retention, but very few cases have been reported to date. The aim of our study was to describe our experience with this rare complication of a patency capsule. Methods: This was a multicenter retrospective case series. The medical records of patients who underwent a patency capsule test were scanned and all cases of symptomatic retention were collected. Results: In total, 20 symptomatic cases of retention out of 1615 (1.2 %) patency capsule tests were identified; in one patient, the patency capsule was retained in the esophagus, in the rest, the capsule was detected in the small bowel resulting in abdominal pain or small-bowel obstruction. One patient (5 %) required surgery; all other patients resolved spontaneously or after corticosteroid therapy. Conclusions: Symptomatic patency capsule retention is a very rare complication with a favorable prognosis. It should be recognized but its use in patients with suspected small-bowel stenosis should not be discouraged. PMID:27652302

  15. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study

    PubMed Central

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m2 and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox’s analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46–1.91) and 1% (HR = 1.01, 95% CI: 1.01–1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  16. Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study

    PubMed Central

    Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha; Reynolds, Sandra; Aronow, Aaron; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Selnes, Ola A

    2015-01-01

    The Multicenter AIDS Cohort Study (MACS) is one of the largest and longest running studies of the natural and treated history of HIV disease. The Neuropsychological (NP) substudy was begun in 1988 following reports of significant adverse neurological consequences of HIV disease, including dementia. The goal was to characterize the neuropsychological deficits among individuals with HIV disease, and track the natural history of the neurological complications over time. There were three distinct MACS recruitment stages that focused on different groups of HIV-infected men, or men at risk for infection. Initially, a subcohort was evaluated semi-annually with NP tests but, beginning in 2005, the entire group of MACS participants have had NP examinations biannually, unless closer follow-up was warranted. The participants complete a battery of NP tests, and are classified as either normal, mildly or severely impaired using the Antinori criteria for HIV-Associated Neurocognitive Disorder (HAND). Additional behavioural data, including mood state and psychoactive substance use, are recorded as part of the main MACS data collection. The MACS public data set (PDS) has been available since 1994 and includes baseline and 6-monthly follow-up data. Beginning in October 1995, the PDS has been released annually with new releases superseding previous versions. PMID:24771276

  17. Multicenter Study of Prevalence of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis in France ▿

    PubMed Central

    Roux, Anne-Laure; Catherinot, Emilie; Ripoll, Fabienne; Soismier, Nathalie; Macheras, Edouard; Ravilly, Sophie; Bellis, Gil; Vibet, Marie-Anne; Le Roux, Evelyne; Lemonnier, Lydie; Gutierrez, Cristina; Vincent, Véronique; Fauroux, Brigitte; Rottman, Martin; Guillemot, Didier; Gaillard, Jean-Louis

    2009-01-01

    We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The “new” species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%). PMID:19846643

  18. Multicenter Study of Antimicrobial Susceptibility of Anaerobic Bacteria in Korea in 2012

    PubMed Central

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

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions Piperacillin-tazobactam, cefoxitin, and carbapemems are highly active β-lactam agents against most of the anaerobes. The resistance rates to moxifloxacin and tigecycline are slightly higher than those in the previous study. PMID:26206683

  19. VAC® therapy a therapeutic alternative in giant omphalocele treatment: a multicenter study.

    PubMed

    Binet, A; Gelas, T; Jochault-Ritz, S; Noizet, O; Bory, J P; Lefebvre, F; Belouadah, M; James-Robert, I; Aubert, D; Bouche-Pillon Persyn, M A; Poli-Merol, M L; François-Fiquet, C

    2013-12-01

    Giant omphalocele is associated to morbidity and mortality because of the strain the reintegrated herniated mass places on the hemodynamic equilibrium and breathing functions of affected infants. Currently, care management consists in a reintegration in one time or progressive reintegration. We report here a multicenter retrospective study about alternative management by VAC® therapy for giant omphaloceles. The study included three patients (1 girl, 2 boys) presenting with giant omphaloceles, born at full term in three different University Hospitals (prenatal diagnosis, normal karyotype). VAC® therapy was implemented at different times according to the cases (at Day 11, Month 1 and Month 5 after birth). The initial pressure applied was -10 mmHg progressively increased to -50 mmHg. A middle size VAC GranuFoam Silver® Dressing was used in all cases. Wound healing occurred at Month 4 for the first case, Month 6 and Month 8 for the other two. VAC® therapy is a good alternative for the care management of giant omphaloceles with more advantages especially when using prosthetic material. We also aimed at refining the most adapted indications in these specific situations, and finally we envisioned a harmonization of care for these children.

  20. Prospective, Multi-Center Evaluation of the Beckman Coulter Prostate Health Index Using WHO Calibration

    PubMed Central

    Loeb, Stacy; Sokoll, Lori J.; Broyles, Dennis L.; Bangma, Chris H.; van Schaik, Ron H.N.; Klee, George G.; Wei, John T.; Sanda, Martin G.; Partin, Alan W.; Slawin, Kevin M.; Marks, Leonard S.; Mizrahi, Isaac A.; Shin, Sanghyuk S.; Cruz, Amabelle B.; Chan, Daniel W.; Roberts, William L.; Catalona, William J.

    2014-01-01

    Purpose Reported prostate-specific antigen (PSA) values may differ substantially between assays with the Hybritech and World Health Organization (WHO) standardization. [-2]proPSA (p2PSA) and the Beckman Coulter prostate health index (phi) are newly approved serum markers, which are associated with prostate cancer risk and aggressiveness. Our objective was to study the influence of assay standardization on these markers. Materials and Methods PSA, % free PSA (%fPSA), and p2PSA were measured using the Hybritech calibration in 892 men undergoing prostate biopsy from a prospective multicenter study. Phi was calculated as: [p2PSA/ fPSA) × (square root of PSA)]. Performance characteristics of phi for prostate cancer detection were then determined using re-calculated WHO calibration PSA values. Results The median phi was significantly higher in men with prostate cancer compared to those with negative biopsies using the WHO values (47.4 vs 39.8, p<0.001). Phi offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to %fPSA or total PSA using the WHO calibration. Conclusions Phi can be calculated using Hybritech or WHO standardized assays, and significantly improved the prediction of biopsy outcome over %fPSA or PSA alone. PMID:23206426

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

    PubMed Central

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

    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 three-six 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. PMID:27559436

  2. Risk factors for deep sternal wound infection after sternotomy: a prospective, multicenter study.

    PubMed

    1996-06-01

    Several risk factors for deep sternal wound infection after sternotomy remain unclear. To assess and compare risk factors among units, a prospective study included 1830 patients in 10 units during a 4-month period: 960 underwent coronary artery bypass grafting and 870 underwent other procedures. According to the Centers for Disease Control and Prevention definitions, 2.3% of patients (42/1830) acquired a deep sternal wound infection. Independent risk factors for deep sternal wound infection were obesity, coronary artery bypass grafting, reoperation, and postoperative inotropic support. Independent risk factors after coronary artery bypass grafting were obesity, bilateral internal thoracic artery grafting, reoperation, and postoperative inotropic support. In all five of the units usually performing bilateral internal thoracic artery graftings, this procedure was associated with high risk of deep sternal wound infection. Duration of operation was a major risk factor in comparison of the unit with the highest risk of deep sternal wound infection with the other nine units; this suggests that parameters related to the perioperative period were involved. Multicenter surveillance is useful to determine reliable risk factors for deep sternal wound infection, to define a high-risk population before operation, and to assess unit-specific risk factors.

  3. The Use of Benzodiazepines to Facilitate Sexual Assault.

    PubMed

    Montgomery, M A

    2010-01-01

    Benzodiazepines are one of the classes of drugs most commonly associated with drug-facilitated sexual assault. As a widely prescribed class of medications and abused drugs, benzodiazepines are extensively available. Their sedating and amnesic effects make them effective candidates for use in drug-facilitated assaults. Detection methods for benzodiazepines and their metabolites in biological fluids are plentiful, but methods must be tailored to the low concentrations of drugs and metabolites expected to be encountered in these cases.

  4. Electronic health records to facilitate clinical research.

    PubMed

    Cowie, Martin R; Blomster, Juuso I; Curtis, Lesley H; Duclaux, Sylvie; Ford, Ian; Fritz, Fleur; Goldman, Samantha; Janmohamed, Salim; Kreuzer, Jörg; Leenay, Mark; Michel, Alexander; Ong, Seleen; Pell, Jill P; Southworth, Mary Ross; Stough, Wendy Gattis; Thoenes, Martin; Zannad, Faiez; Zalewski, Andrew

    2017-01-01

    Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

  5. HASE: Framework for efficient high-dimensional association analyses

    PubMed Central

    Roshchupkin, G. V.; Adams, H. H. H.; Vernooij, M. W.; Hofman, A.; Van Duijn, C. M.; Ikram, M. A.; Niessen, W. J.

    2016-01-01

    High-throughput technology can now provide rich information on a person’s biological makeup and environmental surroundings. Important discoveries have been made by relating these data to various health outcomes in fields such as genomics, proteomics, and medical imaging. However, cross-investigations between several high-throughput technologies remain impractical due to demanding computational requirements (hundreds of years of computing resources) and unsuitability for collaborative settings (terabytes of data to share). Here we introduce the HASE framework that overcomes both of these issues. Our approach dramatically reduces computational time from years to only hours and also requires several gigabytes to be exchanged between collaborators. We implemented a novel meta-analytical method that yields identical power as pooled analyses without the need of sharing individual participant data. The efficiency of the framework is illustrated by associating 9 million genetic variants with 1.5 million brain imaging voxels in three cohorts (total N = 4,034) followed by meta-analysis, on a standard computational infrastructure. These experiments indicate that HASE facilitates high-dimensional association studies enabling large multicenter association studies for future discoveries. PMID:27782180

  6. Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A Multi-Center Study in Korea

    PubMed Central

    Lee, Jung Pyo; Bae, Eunjin; Kang, Eunjeong; Kim, Hack-Lyoung; Kim, Yong-Jin; Oh, Yun Kyu; Kim, Yon Su; Kim, Young Hoon; Lim, Chun Soo

    2016-01-01

    Background Pre-transplant cardiovascular (CV) risk factors affect the development of CV events even after successful kidney transplantation (KT). However, the impact of pre-transplant CV risk factors on allograft failure (GF) has not been reported. Methods and Findings We analyzed the graft outcomes of 2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012. We calculated the pre-transplant CV risk scores based on the Framingham risk model using age, gender, total cholesterol level, smoking status, and history of hypertension. Vascular disease (a composite of ischemic heart disease, peripheral vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients. During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF. In the multivariable-adjusted Cox proportional hazard model, pre-transplant vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI 1.66–3.80). The HR for GF (comparing the highest with the lowest tertile regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22–2.23). In the competing risk model, both pre-transplant vascular disease and CV risk score were independent risk factors for GF. Moreover, the addition of the CV risk score, the pre-transplant vascular disease, or both had a better predictability for GF compared to the traditional GF risk factors. Conclusions In conclusion, both vascular disease and pre-transplant CV risk score were independently associated with GF in this multi-center study. Pre-transplant CV risk assessments could be useful in predicting GF in KT recipients. PMID:27501048

  7. Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post–allogeneic HCT

    PubMed Central

    Abu Zaid, Mohammad; Wu, Juan; Wu, Cindy; Logan, Brent R.; Yu, Jeffrey; Cutler, Corey; Antin, Joseph H.; Paczesny, Sophie

    2017-01-01

    A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT. We measured biomarkers from plasma samples collected in 211 patients using enzyme-linked immunosorbent assay (Tac/Sir = 104, Tac/Mtx = 107). High suppression of tumorigenicity-2 (ST2) and T-cell immunoglobulin mucin-3 (TIM3) at day 28 correlated with 2-year nonrelapse mortality in multivariate analysis (P = .0050, P = .0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49–3.95], P = .0038 and 4.87 [2.53–9.34], P < .0001, respectively). High ST2 and TIM3 correlated with overall survival. Chemokine (C-X-C motif) ligand 9 (CXCL9) levels above the median were associated with chronic GVHD compared with levels below the median in a time-dependent proportional hazard analysis (P = .0069). Low L-Ficolin was associated with hepatic veno-occlusive disease (P = .0053, AUC = 0.80). We confirmed the correlation of plasma-derived proteins, previously assessed in single-center cohorts, with clinical outcomes after allogeneic HCT within this prospective, multicenter study. PMID:27827824

  8. Maternal near miss and death among women with severe hypertensive disorders: a Brazilian multicenter surveillance study

    PubMed Central

    2014-01-01

    Background Hypertensive disorders represent the major cause of maternal morbidity in middle income countries. The main objective of this study was to identify the prevalence and factors associated with severe maternal outcomes in women with severe hypertensive disorders. Methods This was a cross-sectional, multicenter study, including 6706 women with severe hypertensive disorder from 27 maternity hospitals in Brazil. A prospective surveillance of severe maternal morbidity with data collected from medical charts and entered into OpenClinica®, an online system, over a one-year period (2009 to 2010). Women with severe preeclampsia, severe hypertension, eclampsia and HELLP syndrome were included in the study. They were grouped according to outcome in near miss, maternal death and potentially life-threatening condition. Prevalence ratios and 95% confidence intervals adjusted for cluster effect for maternal and perinatal variables and delays in receiving obstetric care were calculated as risk estimates of maternal complications having a severe maternal outcome (near miss or death). Poisson multiple regression analysis was also performed. Results Severe hypertensive disorders were the main cause of severe maternal morbidity (6706/9555); the prevalence of near miss was 4.2 cases per 1000 live births, there were 8.3 cases of Near Miss to 1 Maternal Death and the mortality index was 10.7% (case fatality). Early onset of the disease and postpartum hemorrhage were independent variables associated with severe maternal outcomes, in addition to acute pulmonary edema, previous heart disease and delays in receiving secondary and tertiary care. Conclusions In women with severe hypertensive disorders, the current study identified situations independently associated with a severe maternal outcome, which could be modified by interventions in obstetric care and in the healthcare system. Furthermore, the study showed the feasibility of a hospital system for surveillance of severe

  9. Mastocytosis among elderly patients: A multicenter retrospective French study on 53 patients.

    PubMed

    Rouet, Audrey; Aouba, Achille; Damaj, Gandhi; Soucié, Erinn; Hanssens, Katia; Chandesris, Marie-Olivia; Livideanu, Cristina Bulai; Dutertre, Marine; Durieu, Isabelle; Grandpeix-Guyodo, Catherine; Barète, Stéphane; Bachmeyer, Claude; Soria, Angèle; Frenzel, Laurent; Fain, Olivier; Grosbois, Bernard; de Gennes, Christian; Hamidou, Mohamed; Arlet, Jean-Benoit; Launay, David; Lavigne, Christian; Arock, Michel; Lortholary, Olivier; Dubreuil, Patrice; Hermine, Olivier; Georgin-Lavialle, Sophie

    2016-06-01

    Mastocytosis is a heterogeneous group of diseases with a young median age at diagnosis. Usually indolent and self-limited in childhood, the disease can exhibit aggressive progression in mid-adulthood. Our objectives were to describe the characteristics of the disease when diagnosed among elderly patients, for which rare data are available.The French Reference Center conducted a retrospective multicenter study on 53 patients with mastocytosis >69 years of age, to describe their clinical, biological, and genetic features.The median age of our cohort of patients was 75 years. Mastocytosis variants included were cutaneous (n = 1), indolent systemic (n = 5), aggressive systemic (n = 11), associated with a hematological non-mast cell disease (n = 34), and mast cell leukemia (n = 2). Clinical manifestations were predominantly mast cell activation symptoms (75.5%), poor performance status (50.9%), hepatosplenomegaly (50.9%), skin involvement (49.1%), osteoporosis (47.2%), and portal hypertension and ascites (26.4%). The main biological features were anemia (79.2%), thrombocytopenia (50.9%), leucopenia (20.8%), and liver enzyme abnormalities (32.1%). Of the 40 patients tested, 34 (85%), 2 (5%), and 4 (10%) exhibited the KIT D816V mutant, other KIT mutations and the wild-type form of the KIT gene, respectively. Additional sequencing detected significant genetic defects in 17 of 26 (65.3%) of the patients with associated hematological non-mast cell disease, including TET2, SRSF2, IDH2, and ASLX1 mutations. Death occurred in 19 (35.8%) patients, within a median delay of 9 months, despite the different treatment options available.Mastocytosis among elderly patients has a challenging early detection, rare skin involvement, and/or limited skin disease; it is heterogeneous and has often an aggressive presentation with nonfortuitous associated myeloid lineage malignant clones, and thus a poor overall prognosis.

  10. Multicenter study of posaconazole therapeutic drug monitoring: exposure-response relationship and factors affecting concentration.

    PubMed

    Dolton, Michael J; Ray, John E; Chen, Sharon C-A; Ng, Kingsley; Pont, Lisa; McLachlan, Andrew J

    2012-11-01

    Posaconazole has an important role in the prophylaxis and salvage treatment of invasive fungal infections (IFIs), although poor and variable bioavailability remains an important clinical concern. Therapeutic drug monitoring of posaconazole concentrations has remained contentious, with the use of relatively small patient cohorts in previous studies hindering the assessment of exposure-response relationships. This multicenter retrospective study aimed to investigate relationships between posaconazole concentration and clinical outcomes and adverse events and to assess clinical factors and drug interactions that may affect posaconazole concentrations. Medical records were reviewed for patients who received posaconazole and had ≥1 concentration measured at six hospitals in Australia. Data from 86 patients with 541 posaconazole concentrations were included in the study. Among 72 patients taking posaconazole for prophylaxis against IFIs, 12 patients (17%) developed a breakthrough fungal infection; median posaconazole concentrations were significantly lower than in those who did not develop fungal infection (median [range], 289 [50 to 471] ng/ml versus 485 [0 to 2,035] ng/ml; P < 0.01). The median posaconazole concentration was a significant predictor of breakthrough fungal infection via binary logistic regression (P < 0.05). A multiple linear regression analysis identified a number of significant drug interactions associated with reduced posaconazole exposure, including coadministration with proton pump inhibitors, metoclopramide, phenytoin or rifampin, and the H(2) antagonist ranitidine (P < 0.01). Clinical factors such as mucositis, diarrhea, and the early posttransplant period in hematopoietic stem cell transplant recipients were also associated with reduced posaconazole exposure (P < 0.01). Low posaconazole concentrations are common and are associated with breakthrough fungal infection, supporting the utility of monitoring posaconazole concentrations to ensure

  11. Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

    PubMed Central

    Hill, Michael D.; Martin, Renee H.; Palesch, Yuko Y.; Moy, Claudia S.; Tamariz, Diego; Ryckborst, Karla J.; Jones, Elizabeth B.; Weisman, David; Pettigrew, Creed; Ginsberg, Myron D.

    2015-01-01

    Background Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. Methods Ischemic stroke patients, aged 18–83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. Results Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01–5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3–26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). Conclusions ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. Trial Registration ClincalTrials.gov NCT00235495 PMID:26325387

  12. Learned face-voice pairings facilitate visual search

    PubMed Central

    Zweig, L. Jacob; Suzuki, Satoru; Grabowecky, Marcia

    2014-01-01

    Voices provide a rich source of information that is important for identifying individuals and for social interaction. During search for a face in a crowd, voices often accompany visual information and they facilitate localization of the sought individual. However, it is unclear whether this facilitation occurs primarily because the voice cues the location of the face or because it also increases the salience of the associated face. Here we demonstrate that a voice that provides no location information nonetheless facilitates visual search for an associated face. We trained novel face/voice associations and verified learning using a two-alternative forced-choice task in which participants had to correctly match a presented voice to the associated face. Following training, participants searched for a previously learned target face among other faces while hearing one of the following sounds (localized at the center of the display): a congruent-learned voice, an incongruent but familiar voice, an unlearned and unfamiliar voice, or a time-reversed voice. Only the congruent-learned voice speeded visual search for the associated face. This result suggests that voices facilitate visual detection of associated faces, potentially by increasing their visual salience, and that the underlying crossmodal associations can be established through brief training. PMID:25023955

  13. Learned face-voice pairings facilitate visual search.

    PubMed

    Zweig, L Jacob; Suzuki, Satoru; Grabowecky, Marcia

    2015-04-01

    Voices provide a rich source of information that is important for identifying individuals and for social interaction. During search for a face in a crowd, voices often accompany visual information, and they facilitate localization of the sought-after individual. However, it is unclear whether this facilitation occurs primarily because the voice cues the location of the face or because it also increases the salience of the associated face. Here we demonstrate that a voice that provides no location information nonetheless facilitates visual search for an associated face. We trained novel face-voice associations and verified learning using a two-alternative forced choice task in which participants had to correctly match a presented voice to the associated face. Following training, participants searched for a previously learned target face among other faces while hearing one of the following sounds (localized at the center of the display): a congruent learned voice, an incongruent but familiar voice, an unlearned and unfamiliar voice, or a time-reversed voice. Only the congruent learned voice speeded visual search for the associated face. This result suggests that voices facilitate the visual detection of associated faces, potentially by increasing their visual salience, and that the underlying crossmodal associations can be established through brief training.

  14. Emergency Care for Homeless Patients: A French Multicenter Cohort Study

    PubMed Central

    Feral-Pierssens, Anne-Laure; Aubry, Adeline; Truchot, Jennifer; Raynal, Pierre-Alexis; Boiffier, Mathieu; Hutin, Alice; Leleu, Agathe; Debruyne, Geraud; Joly, Luc-Marie; Juvin, Philippe; Riou, Bruno

    2016-01-01

    Objectives. To determine whether homeless patients experience suboptimal care in the emergency department (ED) by the provision of fewer health care resources. Methods. We conducted a prospective multicenter cohort study in 30 EDs in France. During 72 hours in March 2015, all homeless patients that visited the participating EDs were included in the study. The primary health care service measure was the order by the physician of a diagnostic investigation or provision of a treatment in the ED. Secondary measures of health care services included ED waiting time, number and type of investigations per patient, treatment in the ED, and discharge disposition. Results. A total of 254 homeless patients and 254 nonhomeless patients were included. After excluding homeless patients that attended the ED for the sole purpose of housing, we analyzed 214 homeless and 214 nonhomeless. We found no significant difference between the 2 groups in terms of health care resource consumption, and for our secondary endpoints. Conclusions. We did not find significant differences in the level of medical care delivered in French EDs to homeless patients compared with matched nonhomeless patients. PMID:26985613

  15. The Multi-Center Airborne Coherent Atmospheric Wind Sensor, MACAWS

    NASA Technical Reports Server (NTRS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1997-01-01

    In 1992 the atmospheric lidar remote sensing groups of the NASA Marshall Space Flight Center, NOAA Environmental Technology Laboratory, and Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor, MACAWS, which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in the troposphere and lower stratosphere. A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise which were developed for previous atmospheric research by the respective institutions. The motivation for the MACAWS program Is three-fold: to obtain fundamental measurements of sub-synoptic scale processes and features which may be used as a basis to improve sub-grid scale parameterizations in large-scale models; to obtain similar datasets in order to improve the understanding and predictive capabilities on the mesoscale; and to validate (simulate) the performance of existing (planned) satellite-borne sensors. Examples of the latter include participation in the validation of the NASA Scatterometer and the assessment of prospective satellite Doppler lidar for global tropospheric wind measurement. Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  16. Uterine rupture in pregnancies following myomectomy: A multicenter case series

    PubMed Central

    Kim, Hee-Sun; Oh, Soo-Young; Choi, Suk-Joo; Park, Hyun-Soo; Cho, Geum-Joon; Chung, Jin-Hoon; Seo, Yong-Soo; Jung, Sun-Young; Kim, Jung-Eun; Chae, Su-Hyun

    2016-01-01

    Objective The purpose of this case series was to retrospectively examine records of cases with uterine rupture in pregnancies following myomectomy and to describe the clinical features and pregnancy outcomes. Methods This study was conducted as a multicenter case series. The patient databases at 7 tertiary hospitals were queried. Records of patients with a diagnosis of uterine rupture in the pregnancy following myomectomy between January 2012 and December 2014 were retrospectively collected. The uterine rupture cases enrolled in this study were defined as follows: through-and-through uterine rupture or tear of the uterine muscle and serosa, occurrence from 24+0 to 41+6 weeks’ gestation, singleton pregnancy, and previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status. Results Fourteen pregnant women experienced uterine rupture during their pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks’ gestation occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases had fetal distress. Of the 14 uterine rupture cases, none occurred during labor. All mothers survived and had no sequelae, unlike the perinatal outcomes, although they were receiving blood transfusion or treatment for uterine artery embolization because of uterine atony or massive hemorrhage. Conclusion In women of childbearing age who are scheduled to undergo LTM or LSM, the potential risk of uterine rupture on subsequent pregnancy should be explained before surgery. Pregnancy in women after myomectomy should be carefully observed, and they should be adequately counseled during this period. PMID:27896247

  17. Multicenter Australian trial of islet transplantation: improving accessibility and outcomes.

    PubMed

    O'Connell, P J; Holmes-Walker, D J; Goodman, D; Hawthorne, W J; Loudovaris, T; Gunton, J E; Thomas, H E; Grey, S T; Drogemuller, C J; Ward, G M; Torpy, D J; Coates, P T; Kay, T W

    2013-07-01

    Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation.

  18. The current state of facial prosthetics – A multicenter analysis.

    PubMed

    Thiele, Oliver C; Brom, Jörn; Dunsche, Anton; Ehrenfeld, Michael; Federspil, Philippe; Frerich, Bernhard; Hölzle, Frank; Klein, Martin; Kreppel, Matthias; Kübler, Alexander C; Kübler, Norbert R; Kunkel, Martin; Kuttenberger, Johannes; Lauer, Günter; Mayer, Boris; Mohr, Christopher; Neff, Andreas; Rasse, Michael; Reich, Rudolf H; Reinert, Siegmar; Rothamel, Daniel; Sader, Robert; Schliephake, Henning; Schmelzeisen, Rainer; Schramm, Alexander; Sieg, Peter; Terheyden, Hendrik; Wiltfang, Jörg; Ziegler, Christoph M; Mischkowski, Robert A; Zöller, Joachim E

    2015-09-01

    Even though modern surgical techniques are dominating reconstructive facial procedures, the capability to use facial epitheses for reconstruction is still an important skill for the maxillofacial surgeon. We present an international multicenter analysis to clarify which techniques are used to fixate facial prostheses. We contacted all maxillofacial departments in Germany, Austria, Switzerland and Norway which were registered with the German society for oral and maxillofacial surgery (DGMKG). These centers were asked via electronical mail to provide information on the type of epithesis fixation systems currently in use. The return rate from 58 departments was 43.1% (n = 25). Overall, implant fixation was the preferred fixation system (92%). Plates were the second most common fixation technique (32%). No centers reported the standard use of non-invasive fixation techniques for permanent epithesis fixation. The main retention systems in use were magnets (24/25), other retention systems are used much less often. The current preferred fixation technique for facial epitheses consists of implant-based, magnet-fixated epitheses. For nasal prostheses, a plate-based, magnet-fixated system is often used.

  19. [National multicenter survey: the use of intravenous antimicrobial agents].

    PubMed

    Gutiérrez Zufiaurre, M N; García-Rodríguez, J A

    2006-12-01

    Infectious diseases are currently one of the major health problems worldwide. As a consequence, both nosocomial and community-acquired infections are responsible for a significant increase in workload and health costs for hospitals, particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The use of intravenous antimicrobial agents is common in hospitalized patients. In order to determine the use of antimicrobial agents and the most frequent procedures used for their administration in Spanish hospitals, a national multicenter survey was undertaken among ICU, Internal Medicine and Surgery health staff from 63 hospitals, in which data were collected on central and peripheral catheter manipulation and intravenous administration. Results showed that, in Spain, both catheter manipulation (insertion, maintenance and removal) and administration of antimicrobial agents are performed by the nursing staff following established protocols, particularly for central catheters. Moreover, the ICUs had the highest rates of catheter-bearing patients, as well as patients undergoing antimicrobial treatment, sometimes in combination. The use of intravenous antimicrobial agents in Spanish hospitals results in an increased workload for the nursing staff and higher health costs, not to mention the risk involved with the use of vascular catheters.

  20. Multi-center airborne coherent atmospheric wind sensor (MACAWS)

    SciTech Connect

    Rothermel, J.; Menzies, R.T.; Tratt, D.M.

    1996-11-01

    The Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS) is an airborne scanning coherent Doppler lidar designed to acquire remote multi-dimensional measurements of winds and absolute aerosol backscatter in the troposphere and lower stratosphere. These measurements enable study of atmospheric dynamic processes and features at scales of motion that may be undersampled by, or may be beyond the capability of, existing or planned sensors. MACAWS capabilities enable more realistic assessments of concepts in global tropospheric wind measurement with satellite Doppler lidar, as well as a unique capability to validate the NASA Scatterometer currently scheduled for launch in late 1996. MACAWS consists of a Joule-class CO{sub 2} coherent Doppler lidar on a ruggedized optical table, a programmable scanner to direct the lidar beam in the desired direction, and a dedicated inertial navigation system to account for variable aircraft attitude and speed. MACAWS was flown for the first time in September 1995, over the eastern Pacific Ocean and western US. 33 refs., 2 figs.

  1. Cardiac bioassist: results of the French multicenter cardiomyoplasty study.

    PubMed

    Chachques, Juan C; Jegaden, Olivier; Mesana, Thierry; Glock, Yves; Grandjean, Pierre A; Carpentier, Alain F

    2009-12-01

    The French multicenter experience (6 centers) of dynamic cardiomyoplasty was analyzed for long-term survival and functional outcome, the most important endpoints in congestive heart failure therapy. Cardiomyoplasty was performed in 212 patients with symptoms of chronic heart failure despite maximal pharmacological therapy. The etiology was ischemic (48%), idiopathic (45%) or other (7%). Cardiomyoplasty was performed using the latissimus dorsi muscle which was electrostimulated after surgery. During follow-up, 88% of patients improved clinically. Hospital death occurred in 29 (14%) patients and was related to the severity of preoperative heart failure symptoms. Late mortality occurred in 99 patients due to heart failure (44%), sudden death (37%), or noncardiac causes (18%). Combined dynamic cardiomyoplasty and implantation of a cardiac rhythm management system was safely achieved in 22 patients, and 26 underwent heart transplantation for recurrent heart failure. Long-term functional improvements were observed in most patients, and the best outcome was achieved in those with isolated right ventricular failure. Dynamic cardiomyoplasty can be considered as a destination therapy or a mid- to long-term biological bridge to heart transplantation.

  2. Clinical and pharmacogenomic data mining: 2. A simple method for the combination of information from associations and multivariances to facilitate analysis, decision, and design in clinical research and practice.

    PubMed

    Robson, Barry; Mushlin, Richard

    2004-01-01

    The physician and researcher must ultimately be able to combine qualitative and quantitative features from a variety of combinations of observations on data of many component items (i.e., many dimensions), and hence reach simple conclusions about interpretation, rational courses of action, and design. In the first paper of this series, it was noted that such needs are challenging the classical means of using statistics. Hence, the paper proposed the use of a Generalized Theory of Expected Information or "Zeta Theory". The conjoint event [a,b,c,..] is seen as a rule of association for a,b,c,.. associated with a rule strength I(a;b;c;...) = xi(s,o[a,b,c,..]) - xi (s,e[a,b,c,...]), where xi is the incomplete Zeta Function. Here, o[a,b,c,...] is the observed, and e[a,b,c,..] the expected, frequency of occurrence of conjoint event [a,b,c,...]. The present paper explores how output from this approach might be assembled in a form better suited for decision support. Related to this is the difficulty that the treatment of covariance and multivariance was previously rendered as a "fuzzy association" so that the output would fall into a similar form as the true associations, but this was a somewhat ad hoc approach in which only the final I( ) had any meaning. Users at clinical research sites had subsequently requested an alternative approach in which "effective frequencies" o[ ] and e[ ] calculated from the above variances and used to evaluate I( ) give some intuitive feeling analogous to the association treatment, and this is explored here. Though the present paper is theoretical, real examples are used to illustrate application. One clinical-genomic example illustrates experimental design by identifying data which is, or is not, statistically germane to the study. We also report on some impressions based on applying these techniques in studies of real, extensive patient record data which are now emerging, as well as on molecular design data originally studied in part to

  3. Stochastic facilitation in the brain?

    NASA Astrophysics Data System (ADS)

    Ward, Lawrence M.; Greenwood, Priscilla E.

    2016-05-01

    We describe the context for three unsolved problems of noise in the brain as well as provide some new results relevant to one of them. The problems are: are neural oscillations better described as noisy limit cycles or as noise-driven quasicycles, does noise facilitate synchronization and information transmission in the brain, and do noise-driven spatial patterns (quasipatterns) coexist with noise-driven quasicycles in the brain? We provide a few new results indicating that, in models at least, spatial quasipatterns of quasicycles can occur, and resemble patterns observed in other areas, such as predator-prey systems and chemical reactions.

  4. Trait divergence and indirect interactions allow facilitation of congeneric species

    PubMed Central

    Beltrán, Elisa; Valiente-Banuet, Alfonso; Verdú, Miguel

    2012-01-01

    Background Plant facilitation occurs when the presence of a plant (i.e. a nurse plant) modifies the environment, making it more favourable for the establishment and survival of other species (i.e. facilitated plants), which can germinate and grow nearby. Facilitative associations can be maintained or turned into competition as the facilitated seedling grows. According to the competition-relatedness hypothesis that suggests that closely related species tend to compete more, facilitation turns into competition between phylogenetically close species. However, some examples of facilitation between congeneric species, which are supposed to be closely related species, have been found in nature. Scope In this work, some examples of congeneric facilitation and subsequent coexistence are reviewed and an attempt is made to explain those exceptions to the competition-relatedness hypothesis. Conclusions Two mechanisms are proposed that can switch the facilitation–competition balance: trait divergence and indirect interactions. When traits have diverged within the genus, the niche overlap is reduced and competition relaxed, thus allowing the coexistence of congeneric species. The presence of third interplayers (mycorrhizal fungi, seed dispersers, pollinators or pathogens) participating in the interaction between plants can alleviate the competition or enhance the reproduction and allow the coexistence of species that could not coexist in their absence. PMID:22543178

  5. Coordination and management of multicenter clinical studies in trauma: Experience from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study

    PubMed Central

    Rahbar, Mohammad H.; Fox, Erin E.; del Junco, Deborah J.; Cotton, Bryan A.; Podbielski, Jeanette M.; Matijevic, Nena; Cohen, Mitchell J.; Schreiber, Martin A.; Zhang, Jiajie; Mirhaji, Parsa; Duran, Sarah; Reynolds, Robert J.; Benjamin-Garner, Ruby; Holcomb, John B.

    2011-01-01

    Aim Early death due to hemorrhage is a major consequence of traumatic injury. Transfusion practices differ among hospitals and it is unknown which transfusion practices improve survival. This report describes the experience of the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study Data Coordination Center in designing and coordinating a study to examine transfusion practices at ten Level 1 trauma centers in the U.S. Methods PROMMTT was a multisite prospective observational study of severely injured transfused trauma patients. The clinical sites collected real-time information on the timing and amounts of blood product infusions as well as colloids and crystalloids, vital signs, initial diagnostic and clinical laboratory tests, life saving interventions and other clinical care data. Results Between July 2009 and October 2010, PROMMTT screened 12,561 trauma admissions and enrolled 1,245 patients who received one or more blood transfusions within 6 hours of ED admission. A total of 297 massive transfusions were observed over the course of the study at a combined rate of 5.0 massive transfusion patients/week. Conclusion PROMMTT is the first multisite study to collect real-time prospective data on trauma patients requiring transfusion. Support from the Department of Defense and collaborative expertise from the ten participating centers helped to demonstrate the feasibility of prospective trauma transfusion studies. The observational data collected from this study will be an invaluable resource for research in trauma surgery and it will guide the design and conduct of future randomized trials. PMID:22001613

  6. The Role of the Facilitator in Couple Relationship Education.

    PubMed

    Ketring, Scott A; Bradford, Angela B; Davis, Stephanie Y; Adler-Baeder, Francesca; McGill, Julianne; Smith, Thomas A

    2017-03-11

    While much of the Couple Relationship Education (CRE) research has focused on participant factors, unexpectedly little research has considered how characteristics of those providing the programming shape its efficacy. The current study draws upon a diverse sample of 225 couples who received CRE from community educators to examine how facilitation alliance is related to relationship outcomes for men and women and whether having a facilitator with similar demographic characteristics is related to the alliance. Results suggest that the facilitation alliance is related to some-though not all-postprogram outcomes and these effects were uniform across gender and relationship status (married vs. unmarried). Having a facilitator of the same gender was associated with a stronger alliance. Implications are discussed.

  7. The endoplasmic reticulum–associated Hsp40 DNAJB12 and Hsc70 cooperate to facilitate RMA1 E3–dependent degradation of nascent CFTRΔF508

    PubMed Central

    Grove, Diane E.; Fan, Chun-Yang; Ren, Hong Yu; Cyr, Douglas M.

    2011-01-01

    Relative contributions of folding kinetics versus protein quality control (QC) activity in the partitioning of non-native proteins between life and death are not clear. Cystic fibrosis transmembrane conductance regulator (CFTR) biogenesis serves as an excellent model to study this question because folding of nascent CFTR is inefficient and deletion of F508 causes accumulation of CFTRΔF508 in a kinetically trapped, but foldable state. Herein, a novel endoplasmic reticulum (ER)-associated Hsp40, DNAJB12 (JB12) is demonstrated to play a role in control of CFTR folding efficiency. JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. Modest elevation of JB12 decreased nascent CFTR and CFTRΔF508 accumulation while increasing association of Hsc70 with ER forms of CFTR and the RMA1 E3 complex. Depletion of JB12 increased CFTR folding efficiency up to threefold and permitted a pool of CFTRΔF508 to fold and escape the ER. Introduction of the V510D misfolding suppressor mutation into CFTRΔF508 modestly increased folding efficiency, whereas combined inactivation of JB12 and suppression of intrinsic folding defects permitted CFTRΔF508 to fold at 50% of wild-type efficiency. Therapeutic correction of CFTRΔF508 misfolding in cystic fibrosis patients may require repair of defective folding kinetics and suppression of ER QC factors, such as JB12. PMID:21148293

  8. Actual preoperative fasting time in Brazilian hospitals: the BIGFAST multicenter study

    PubMed Central

    de Aguilar-Nascimento, José E; de Almeida Dias, Ana L; Dock-Nascimento, Diana B; Correia, Maria Isabel TD; Campos, Antonio CL; Portari-Filho, Pedro Eder; Oliveira, Sergio S

    2014-01-01

    Background Prolonged fasting increases organic response to trauma. This multicenter study investigated the gap between the prescribed and the actual preoperative fasting times in Brazilian hospitals and factors associated with this gap. Methods Patients (18–90-years-old) who underwent elective operations between August 2011 and September 2012 were included in the study. The actual and prescribed times for fasting were collected and correlated with sex, age, surgical disease (malignancies or benign disease), operation type, American Society of Anesthesiologists score, type of hospital (public or private), and nutritional status. Results A total of 3,715 patients (58.1% females) with a median age of 49 (18–94) years from 16 Brazilian hospitals entered the study. The median (range) preoperative fasting time was 12 (2–216) hours, and fasting time was longer (P<0.001) in hospitals using a traditional fasting protocol (13 [6–216] hours) than in others that had adopted new guidelines (8 [2–48] hours). Almost 80% (n=2,962) of the patients were operated on after 8 or more hours of fasting and 46.2% (n=1,718) after more than 12 hours. Prolonged fasting was not associated with physical score, age, sex, type of surgery, or type of hospital. Patients operated on due to a benign disease had an extended duration of preoperative fasting. Conclusion Actual preoperative fasting time is significantly longer than prescribed fasting time in Brazilian hospitals. Most of these hospitals still adopt traditional rather than modern fasting guidelines. All patients are at risk of long periods of fasting, especially those in hospitals that follow traditional practices. PMID:24627636

  9. Kidney Dysfunction and Markers of Inflammation in the Multicenter AIDS Cohort Study

    PubMed Central

    Abraham, Alison G.; Darilay, Annie; McKay, Heather; Margolick, Joseph B.; Estrella, Michelle M.; Palella, Frank J.; Bolan, Robert; Rinaldo, Charles R.; Jacobson, Lisa P.

    2015-01-01

    Background. Human immunodeficiency virus (HIV)–infected individuals are at higher risk for chronic kidney disease than HIV-uninfected individuals. We investigated whether the inflammation present in treated HIV infection contributes to kidney dysfunction among HIV-infected men receiving highly active antiretroviral therapy. Methods. The glomerular filtration rate (GFR) was directly measured (using iohexol) along with 12 markers of inflammation in Multicenter AIDS Cohort Study participants. Exploratory factor analysis was used to identify inflammatory processes related to kidney dysfunction. The estimated levels of these inflammatory processes were used in adjusted logistic regression analyses evaluating cross-sectional associations with kidney function outcomes. Results. There were 434 HIV-infected men receiving highly active antiretroviral therapy and 200 HIV-uninfected men. HIV-infected men were younger (median age, 51 vs 53 years) and had higher urine protein-creatinine ratios (median, 98 vs 66 mg/g) but comparable GFRs (median, 109 vs 106 mL/min|1.73 m2). We found an inflammatory process dominated by markers: soluble tumor necrosis factor receptor 2, soluble interleukin 2 receptor α, soluble gp130, soluble CD27, and soluble CD14. An increase of 1 standard deviation in that inflammatory process was associated with significantly greater odds of GFR ≤90 mL/min/1.73 m2 (odds ratio, 2.0) and urine protein >200 mg/g (odds ratio, 2.3). Conclusions. Higher circulating levels of immune activation markers among treated HIV-infected men may partially explain their higher burden of kidney dysfunction compared with uninfected men. PMID:25762788

  10. Mixed Membership Trajectory Models of Cognitive Impairment in the Multicenter AIDS Cohort Study

    PubMed Central

    Molsberry, Samantha A.; Lecci, Fabrizio; Kingsley, Lawrence; Junker, Brian; Reynolds, Sandra; Goodkin, Karl; Levine, Andrew J.; Martin, Eileen; Miller, Eric N.; Munro, Cynthia A.; Ragin, Ann; Sacktor, Ned; Becker, James T.

    2016-01-01

    Objective The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the “closeness” of an individual to one of the canonical trajectories. Design The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV Disease among gay and bisexual men. Methods Using data from 3,892 men (both HIV-infected and uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual’s “closeness” to these trajectories. Results We identified three distinct trajectories to cognitive impairment – one “normal aging” (low probability of mild impairment until age 60), one “premature aging” (mild impairment starting at age 45–50), and one “unhealthy” (mild impairment in 20s and 30s) profile. Second, clinically defined AIDS and not simply HIV Disease, was associated with closeness to the premature aging trajectory. And, third, Hepatitis-C infection, Depression, Race, Recruitment Cohort and Confounding Conditions all affected individual’s closeness to these trajectories. Conclusions These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment. PMID:25565498

  11. Italian symptomatic intracranial atherosclerosis study (ISIDE) : A multicenter transcranial ultrasound evaluation.

    PubMed

    Baracchini, Claudio; Anzola, Gian Paolo; Cenciarelli, Silvia; Diomedi, Marina; Bella, Rita; Tonon, Agnese; Braga, Massimiliano; Zedde, Maria Luisa; Zanferrari, Carla; Del Sette, Massimo; Caliandro, Pietro; Gandolfo, Carlo; Ricci, Stefano; Meneghetti, Giorgio

    2016-10-01

    There are currently no data available on the prevalence of symptomatic intracranial atherosclerosis (ICAS) in Italy. The aim of this prospective, multicenter, hospital-based, transcranial ultrasound study was to establish the prevalence of ICAS among patients hospitalized with acute ischemic stroke. At 11 stroke centers across Italy, patients consecutively admitted for their first ever acute ischemic stroke were assessed prospectively over a 24-month period either with transcranial color-coded Doppler sonography (TCCS) or transcranial Doppler (TCD) according to validated criteria. ICAS was diagnosed when there was an evidence of a cerebral infarction in the territory of a ≥50 % stenosis detected by TCCS/TCD and confirmed by magnetic resonance angiography or computed tomography angiography. A total of 1134 patients were enrolled, 665 of them (58.6 %) men, with a mean age of 71.2 ± 13.3 years. ICAS was recorded in 99 patients (8.7 % of the whole sample, 8.9 % among Caucasians), most commonly located in the anterior circulation (63 of 99, 5.5 %). After adjusting for potential confounders, multivariate analysis identified carotid/vertebral ≥50 % stenosis [odds ratio (OR) 2.59, 95 % (confidence interval) CI 1.77-6.33; P = 0.02] and hypercholesterolemia (OR 1.38, 95 % CI 1.02-1.89; P = 0.02) as being independently associated with ICAS. ICAS is a surprisingly relevant cause of ischemic stroke in Italy, identified in almost 9 % of first-ever stroke patients. It is more prevalent in the anterior circulation and independently associated with hemodynamically significant cervical vessel atherosclerosis and hypercholesterolemia. These findings support the systematic use of transcranial ultrasound to identify ICAS in patients presenting with acute ischemic stroke and in cases with ≥50 % cervical vessel stenoses.

  12. The Influence of Facilitator and Facilitation Characteristics on Participants' Ratings of Stepfamily Education

    ERIC Educational Resources Information Center

    Higginbotham, Brian J.; Myler, Cory

    2010-01-01

    We examine the relative importance of facilitator and facilitation characteristics on participant ratings of a stepfamily education program. Data from 48 facilitators and 598 participants suggest that quality facilitation is more meaningful to participants than whether facilitators have comparable demographic characteristics or life experiences.…

  13. A modular informatics platform for effective support of collaborative and multicenter studies in cardiology.

    PubMed

    Marinelli, Martina; Positano, Vincenzo; Lorenzoni, Valentina; Caselli, Chiara; Mangione, Maurizio; Marcheschi, Paolo; Puzzuoli, Stefano; Esposito, Natalia; L'Abbate, Giuseppe Andrea; Neglia, Danilo

    2016-12-01

    Collaborative and multicenter studies permit a large number of patients to be enrolled within a reasonable time and providing the opportunity to collect different data. Informatics platforms play an important role in management, storage, and exchange of data between the participants involved in the study. In this article, we describe a modular informatics platform designed and developed to support collaborative and multicenter studies in cardiology. In each developed module, data management is implemented following local defined protocols. The modular characteristic of the developed platform allows independent transfer of different kinds of data, such as biological samples, imaging raw data, and patients' digital information. Moreover, it offers safe central storage of the data collected during the study. The developed platform was successfully tested during a European collaborative and multicenter study, focused on evaluating multimodal non-invasive imaging to diagnose and characterize ischemic heart disease.

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

    PubMed

    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.

  15. Volatility and Growth in Populations of Rural Associations

    ERIC Educational Resources Information Center

    Wollebaek, Dag

    2010-01-01

    This article uses unique community-level data aggregated from censuses of associations to analyze growth and volatility in rural populations of grassroots associations. A qualitative comparative analysis (QCA) shows that the two main paths to growth were (1) centralization in polycephalous (multicentered) municipalities and (2) population growth…

  16. Characterization of chronic arthritis in a multicenter study of 852 childhood-onset systemic lupus erythematosus patients.

    PubMed

    Sakamoto, Ana Paula; Silva, Clovis Artur; Ferriani, Mariana Paes Leme; Pereira, Rosa Maria Rodrigues; Bonfá, Eloisa; Saad-Magalhães, Claudia; Okuda, Eunice; Appenzeller, Simone; Gomes, Francisco Hugo; Cunha, Ana Luiza Garcia; Salume, Mirna Henriques Tomich; Piotto, Daniela Petry; Terreri, Maria Teresa

    2016-12-01

    Chronic arthritis (CA) is an unusual condition in childhood-onset systemic lupus erythematosus (cSLE) and data in children is very limited. The aim of the study is to assess CA in a large population of cSLE patients, in a multicenter cross-sectional study including 852 cSLE patients followed in ten Pediatric Rheumatology referral services in state of São Paulo, Brazil. CA was observed in 32/852 (3.7 %) cSLE patients mostly in hands and ankles. Chronic monoarthritis was diagnosed in four cSLE patients, oligoarthritis in nine and polyarthritis in 19. In the latter group, six had rhupus syndrome. Two oligoarticular patients had Jaccoud's arthropathy. CA was an isolated manifestation observed at disease onset in 13/32 (41 %) cSLE patients, and juvenile idiopathic arthritis (JIA) was the first diagnosis in 18/32 (56 %). The comparison of last visit of patients with CA and without this manifestation revealed higher frequency of splenomegaly (28 vs. 11 %, p = 0.002). The median of SLICC/ACR-DI score [1(0-9) vs. 0(0-7), p = 0.003] was significantly higher in CA patients compared to patients without this manifestation, likewise the frequency of musculoskeletal damage (31 vs. 9 % p = 0.001). Frequencies of treatment with nonsteroidal anti-inflammatory drugs (75 vs. 26 %, p < 0.0001), hydroxychloroquine sulfate (87 vs. 59 %, p = 0.001) and methotrexate (47 vs. 22 %, p = 0.001) were significantly higher in CA patients. This large multicenter study allowed us to characterize CA as a rare and early manifestation of cSLE, frequently mimicking JIA at disease onset. It is predominantly polyarticular, involving more often hands and ankles and it is associated with significant musculoskeletal accrual damage.

  17. Facilitating submetering implementation. Final report

    SciTech Connect

    Bowers, M.A.

    1996-05-01

    Residential submetering is the measurement and billing of electric use in individual apartments in master-metered buildings. In master-metered building situations, residents do not bear electricity costs in proportion to consumption levels. As a result, studies have confirmed that residents in master-metered buildings tend to consume more electricity than residents with individual apartment metering, and have established electrical submetering as an effective energy conservation measure. The New York State Energy Research & Development Authority (NYSERDA) has commissioned a project called Facilitating Submetering Implementation to identify and analyze barriers to the implementation of residential electrical submetering in New York and to formulate recommendations that would facilitate the removal of these barriers, streamlining the process. Experienced professionals in the technical, legal, regulatory, analytical, financial, and other aspects of submetering were retained to interview key interested parties and conduct public forums. This and other data were then analyzed to ascertain the barriers to submetering and develop recommendations designed to reduce or eliminate these barriers. The key barriers to submetering implementation were found to be the Public Service Commission (PSC) requirement for a vote of a majority of shareholders (for coops and condos) and the high initial cost that cannot easily be recouped by owners of both rental and shareholder-owned buildings. The key recommendations are to repeal the voting requirement, maintain the utility incentives, adopt a uniform dispute resolution mechanism, and increase awareness through an Ad-hoc Submetering Committee and supporting educational materials. Other funding sources not fully available can also be made available with regulatory agency support.

  18. Semantic facilitation in bilingual first language acquisition.

    PubMed

    Bilson, Samuel; Yoshida, Hanako; Tran, Crystal D; Woods, Elizabeth A; Hills, Thomas T

    2015-07-01

    Bilingual first language learners face unique challenges that may influence the rate and order of early word learning relative to monolinguals. A comparison of the productive vocabularies of 435 children between the ages of 6 months and 7 years-181 of which were bilingual English learners-found that monolinguals learned both English words and all-language concepts faster than bilinguals. However, bilinguals showed an enhancement of an effect previously found in monolinguals-the preference for learning words with more associative cues. Though both monolinguals and bilinguals were best fit by a similar model of word learning, semantic network structure and growth indicated that the two groups were learning English words in a different order. Further, in comparison with a model of two-monolinguals-in-one-mind, bilinguals overproduced translational equivalents. Our results support an emergent account of bilingual first language acquisition, where learning a word in one language facilitates its acquisition in a second language.

  19. Managing Multi-center Flow Cytometry Data for Immune Monitoring.

    PubMed

    White, Scott; Laske, Karoline; Welters, Marij Jp; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1-5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21-23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables automated

  20. Managing Multi-center Flow Cytometry Data for Immune Monitoring

    PubMed Central

    White, Scott; Laske, Karoline; Welters, Marij JP; Bidmon, Nicole; van der Burg, Sjoerd H; Britten, Cedrik M; Enzor, Jennifer; Staats, Janet; Weinhold, Kent J; Gouttefangeas, Cécile; Chan, Cliburn

    2014-01-01

    With the recent results of promising cancer vaccines and immunotherapy1–5, immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a rate of tens of thousands of cells per second. Given the complexity of flow cytometry assays, reproducibility is a major concern, especially for multi-center studies. A promising approach for improving reproducibility is the use of automated analysis borrowing from statistics, machine learning and information visualization21–23, as these methods directly address the subjectivity, operator-dependence, labor-intensive and low fidelity of manual analysis. However, it is quite time-consuming to investigate and test new automated analysis techniques on large data sets without some centralized information management system. For large-scale automated analysis to be practical, the presence of consistent and high-quality data linked to the raw FCS files is indispensable. In particular, the use of machine-readable standard vocabularies to characterize channel metadata is essential when constructing analytic pipelines to avoid errors in processing, analysis and interpretation of results. For automation, this high-quality metadata needs to be programmatically accessible, implying the need for a consistent Application Programming Interface (API). In this manuscript, we propose that upfront time spent normalizing flow cytometry data to conform to carefully designed data models enables

  1. Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS)

    NASA Astrophysics Data System (ADS)

    Rhothermel, Jeffry; Jones, W. D.; Dunkin, J. A.; McCaul, E. W., Jr.

    1993-01-01

    This effort involves development of a calibrated, pulsed coherent CO2 Doppler lidar, followed by a carefully-planned and -executed program of multi-dimensional wind velocity and aerosol backscatter measurements from the NASA DC-8 research aircraft. The lidar, designated as the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), will be applicable to two research areas. First, MACAWS will enable specialized measurements of atmospheric dynamical processes in the planetary boundary layer and free troposphere in geographic locations and over scales of motion not routinely or easily accessible to conventional sensors. The proposed observations will contribute fundamentally to a greater understanding of the role of the mesoscale, helping to improve predictive capabilities for mesoscale phenomena and to provide insights into improving model parameterizations of sub-grid scale processes within large-scale circulation models. As such, it has the potential to contribute uniquely to major, multi-institutional field programs planned for the mid 1990's. Second, MACAWS measurements can be used to reduce the degree of uncertainty in performance assessments and algorithm development for NASA's prospective Laser Atmospheric Wind Sounder (LAWS), which has no space-based instrument heritage. Ground-based lidar measurements alone are insufficient to address all of the key issues. To minimize costs, MACAWS is being developed cooperatively by the lidar remote sensing groups of the Jet Propulsion Laboratory, NOAA Wave Propagation Laboratory, and MSFC using existing lidar hardware and manpower resources. Several lidar components have already been exercised in previous airborne lidar programs (for example, MSFC Airborne Doppler Lidar System (ADLS) used in 1981,4 Severe Storms Wind Measurement Program; JPL Airborne Backscatter Lidar Experiment (ABLE) used in 1989,90 Global Backscatter Experiment Survey Missions). MSFC has been given responsibility for directing the overall

  2. The Multi-center Airborne Coherent Atmospheric Wind Sensor.

    NASA Astrophysics Data System (ADS)

    Rothermel, Jeffry; Cutten, Dean R.; Hardesty, R. Michael; Menzies, Robert T.; Howell, James N.; Johnson, Steven C.; Tratt, David M.; Olivier, Lisa D.; Banta, Robert M.

    1998-04-01

    In 1992 the atmospheric lidar remote sensing groups of the National Aeronautics and Space Administration Marshall Space Flight Center, the National Oceanic and Atmospheric Administration/Environmental Technology Laboratory (NOAA/ETL), and the Jet Propulsion Laboratory began a joint collaboration to develop an airborne high-energy Doppler laser radar (lidar) system for atmospheric research and satellite validation and simulation studies. The result is the Multi-center Airborne Coherent Atmospheric Wind Sensor (MACAWS), which has the capability to remotely sense the distribution of wind and absolute aerosol backscatter in three-dimensional volumes in the troposphere and lower stratosphere.A factor critical to the programmatic feasibility and technical success of this collaboration has been the utilization of existing components and expertise that were developed for previous atmospheric research by the respective institutions. For example, the laser transmitter is that of the mobile ground-based Doppler lidar system developed and used in atmospheric research for more than a decade at NOAA/ETL.The motivation for MACAWS is threefold: 1) to obtain fundamental measurements of subsynoptic-scale processes and features to improve subgrid-scale parameterizations in large-scale models, 2) to obtain datasets in order to improve the understanding of and predictive capabilities for meteorological systems on subsynoptic scales, and 3) to validate (simulate) the performance of existing (planned) satellite-borne sensors.Initial flight tests were made in September 1995; subsequent flights were made in June 1996 following system improvements. This paper describes the MACAWS instrument, principles of operation, examples of measurements over the eastern Pacific Ocean and western United States, and future applications.

  3. Multicenter Comparison of Seven 25OH Vitamin D Automated Immunoassays

    PubMed Central

    Lippi, Giuseppe; Salvagno, Gian Luca; Fortunato, Antonio; Dipalo, Mariella; Aloe, Rosalia; Da Rin, Giorgio; Giavarina, Davide

    2015-01-01

    Summary Background The measurement of 25OH vitamin D continues to grow in clinical laboratories. The aim of this multi-center study was to compare the results of seven automated commercial immunoassays with a reference HPLC technique. Methods One hundred and twenty consecutive outpatient serum samples were centrifuged, divided in aliquots, frozen and shipped to the participating laboratories. 25OH Vitamin D was measured with a reference HPLC system and with seven automated commercial immunoassays (Roche Cobas E601, Beckman Coulter Unicel DXI 800, Ortho Vitros ES, DiaSorin Liaison, Siemens Advia Centaur, Abbott Architect i System and IDS iSYS). Results Compared to the reference method, the regression coefficients ranged from 0.923 to 0.961 (all p<0.001). The slope of Deming fit ranged from 0.95 to 1.06, whereas the intercept was comprised between −15.2 and 9.2 nmol/L. The bias from the reference HPLC technique varied from −14.5 to 8.7 nmol/L. The minimum performance goal for bias was slightly exceeded by only one immunoassay. The agreement between HPLC and the different immunoassays at 50 nmol/L 25OH Vitamin D varied between 0.61 and 0.85 (all p<0.001). The percentage of samples below this cut-off was significantly different with only one immunoassay. Conclusions The excellent correlation with the reference HPLC technique attests that all seven automated immunoassays may be reliably used for routine assessment of 25OH-D in clinical laboratories. The significant bias among the different methods seems mostly attributable to the lack of standardization and calls for additional efforts for improving harmonization of 25OH-D immunoassays. PMID:28356846

  4. Neurophysiology versus clinical genetics in Rett syndrome: A multicenter study

    PubMed Central

    Halbach, Nicky; Julu, Peter; Witt‐Engerström, Ingegerd; Pini, Giorgio; Bigoni, Stefania; Hansen, Stig; Apartopoulos, Flora; Delamont, Robert; van Roozendaal, Kees; Scusa, Maria F.; Borelli, Paolo; Candel, Math; Curfs, Leopold

    2016-01-01

    Many studies have attempted to establish the genotype–phenotype correlation in Rett syndrome (RTT). Cardiorespiratory measurements provide robust objective data, to correlate with each of the different clinical phenotypes. It has important implications for the management and treatment of this syndrome. The aim of this study was to correlate the genotype with the quantitative cardiorespiratory data obtained by neurophysiological measurement combined with a clinical severity score. This international multicenter study was conducted in four European countries from 1999 to 2012. The study cohort consisted of a group of 132 well‐defined RTT females aged between 2 and 43 years with extended clinical, molecular, and neurophysiological assessments. Diagnosis of RTT was based on the consensus criteria for RTT and molecular confirmation. Genotype–phenotype analyses of clinical features and cardiorespiratory data were performed after grouping mutations by the same type and localization or having the same putative biological effect on the MeCP2 protein, and subsequently on eight single recurrent mutations. A less severe phenotype was seen in females with CTS, p.R133C, and p.R294X mutations. Autonomic disturbances were present in all females, and not restricted to nor influenced by one specific group or any single recurrent mutation. The objective information from non‐invasive neurophysiological evaluation of the disturbed central autonomic control is of great importance in helping to organize the lifelong care for females with RTT. Further research is needed to provide insights into the pathogenesis of autonomic dysfunction, and to develop evidence‐based management in RTT. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc. PMID:27354166

  5. Reducing between scanner differences in multi-center PET studies.

    PubMed

    Joshi, Aniket; Koeppe, Robert A; Fessler, Jeffrey A

    2009-05-15

    This work is part of the multi-center Alzheimer's Disease Neuroimaging Initiative (ADNI), a large multi-site study of dementia, including patients having mild cognitive impairment (MCI), probable Alzheimer's disease (AD), as well as healthy elderly controls. A major portion of ADNI involves the use of [(18)F]-fluorodeoxyglucose (FDG) with positron emission tomography (PET). The objective of this paper is the reduction of inter-scanner differences in the FDG-PET scans obtained from the 50 participating PET centers having fifteen different scanner models. In spite of a standardized imaging protocol, systematic inter-scanner variability in PET images from various sites is observed primarily due to differences in scanner resolution, reconstruction techniques, and different implementations of scatter and attenuation corrections. Two correction steps were developed by comparison of 3-D Hoffman brain phantom scans with the 'gold standard' digital 3-D Hoffman brain phantom: i) high frequency correction; where a smoothing kernel for each scanner model was estimated to smooth all images to a common resolution and ii) low frequency correction; where smooth affine correction factors were obtained to reduce the attenuation and scatter correction errors. For the phantom data, the high frequency correction reduced the variability by 20%-50% and the low frequency correction further reduced the differences by another 20%-25%. Correction factors obtained from phantom studies were applied to 95 scans from normal control subjects obtained from the participating sites. The high frequency correction reduced differences similar to the phantom studies. However, the low frequency correction did not further reduce differences; hence further refinement of the procedure is necessary.

  6. The Global Enteric Multicenter Study (GEMS): Impetus, Rationale, and Genesis

    PubMed Central

    Levine, Myron M.; Kotloff, Karen L.; Nataro, James P.; Muhsen, Khitam

    2012-01-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12 600 analyzable cases and 12 600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467 000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease. PMID:23169934

  7. The Global Enteric Multicenter Study (GEMS): impetus, rationale, and genesis.

    PubMed

    Levine, Myron M; Kotloff, Karen L; Nataro, James P; Muhsen, Khitam

    2012-12-01

    Diarrheal disease remains one of the top 2 causes of young child mortality in the developing world. Whereas improvements in water/sanitation infrastructure and hygiene can diminish transmission of enteric pathogens, vaccines can also hasten the decline of diarrheal disease morbidity and mortality. From 1980 through approximately 2004, various case/control and small cohort studies were undertaken to address the etiology of pediatric diarrhea in developing countries. Many studies had methodological limitations and came to divergent conclusions, making it difficult to prioritize the relative importance of different pathogens. Consequently, in the first years of the millennium there was no consensus on what diarrheal disease vaccines should be developed or implemented; however, there was consensus on the need for a well-designed study to obtain information on the etiology and burden of more severe forms of diarrheal disease to guide global investment and implementation decisions. Accordingly, the Global Enteric Multicenter Study (GEMS) was designed to overcome drawbacks of earlier studies and determine the etiology and population-based burden of pediatric diarrheal disease. GEMS, which includes one of the largest case/control studies of an infectious disease syndrome ever undertaken (target approximately 12,600 analyzable cases and 12,600 controls), was rolled out in 4 sites in sub-Saharan Africa (Gambia, Kenya, Mali, Mozambique) and 3 in South Asia (Bangladesh, India, Pakistan), with each site linked to a population under demographic surveillance (total approximately 467,000 child years of observation among children <5 years of age). GEMS data will guide investment and help prioritize strategies to mitigate the morbidity and mortality of pediatric diarrheal disease.

  8. A Multicenter Reference Intervals Study for Specific Proteins in China

    PubMed Central

    Qin, Xuzhen; Tang, Guodong; Qiu, Ling; Li, Peng Chang; Xia, Liangyu; Chen, Ming; Tao, Zhihua; Li, Shijun; Liu, Min; Wang, Liang; Gao, Shang; Yu, Songlin; Cheng, Xinqi; Han, Jianhua; Hou, Li’an; Kawano, Reo; Ichihara, Kiyoshi

    2015-01-01

    Abstract A multicenter study conducted in healthy population of 6 cities from the 4 corners and central China for 7 serum-specific proteins to identify the sources of variation and establish the reference intervals on 2 automation platforms. A total of 3148 subjects aged 19 to 64 years old were enrolled in this study to ensure at least 120 participants in each 10-year age group and each city. The majority of samples were transported to central laboratory and measured on both Beckman AU5800 and Immage 800 analytical systems. Three-level nested ANOVA, multiple regression analysis, and the scatter plot were used to explore the variations from sex, age, region, BMI, cigarette smoking, and so on. The latent abnormal value exclusion (LAVE) method was applied at the time of computing RIs as a method for secondary exclusion. Regionality was not observed in any of the immunoassay in China. Variations for sex were significant for IgM among the immune analytes. For CRP and hsCRP results with turbidimetry method (Beckman Coulter AU5800) were lower than the nephelometry method (Beckman Immage). The LAVE method did not affect the RIs computed for the majority of analytes except C4, CRP, and hsCRP. In the scatter plot at the age of 45 years old C3, C4, and IgM reached an inflection point, accordingly RIs were separated by the age group. With the lack of regional differences and the well-standardized status of test results, the RIs of C3, IgG, IgA, IgM derived from this nationwide study can be used for the entire Chinese population. C4, CRP, and hsCRP were affected by different platforms and gender was a significant source of variation for IgM, so they had separated RIs. PMID:26656356

  9. Analytically reduced form of multicenter integrals from Gaussian transforms. [in atomic and molecular physics

    NASA Technical Reports Server (NTRS)

    Straton, Jack C.

    1989-01-01

    The four-dimensional Fourier-Feynman transformations previously used in analytically reducing the general class of integrals containing multicenter products of 1s hydrogenic orbitals, Coulomb or Yukawa potentials, and plane waves, are replaced by the one-dimensional Gaussian transformation. This reduces the previously required double-diagonalization of the quadratic form of the multicenter integrals to only one diagonalization, yielding a simpler reduced form of the integral. The present work also extends the result to include all s states and pairs of states with l not equal to zero summed over the m quantum number.

  10. The effectiveness of video interaction guidance in parents of premature infants: A multicenter randomised controlled trial

    PubMed Central

    2012-01-01

    Background Studies have consistently found a high incidence of neonatal medical problems, premature births and low birth weights in abused and neglected children. One of the explanations proposed for the relation between neonatal problems and adverse parenting is a possible delay or disturbance in the bonding process between the parent and infant. This hypothesis suggests that due to neonatal problems, the development of an affectionate bond between the parent and the infant is impeded. The disruption of an optimal parent-infant bond -on its turn- may predispose to distorted parent-infant interactions and thus facilitate abusive or neglectful behaviours. Video Interaction Guidance (VIG) is expected to promote the bond between parents and newborns and is expected to diminish non-optimal parenting behaviour. Methods/design This study is a multi-center randomised controlled trial to evaluate the effectiveness of Video Interaction Guidance in parents of premature infants. In this study 210 newborn infants with their parents will be included: n = 70 healthy term infants (>37 weeks GA), n = 70 moderate term infants (32–37 weeks GA) which are recruited from maternity wards of 6 general hospitals and n = 70 extremely preterm infants or very low birth weight infants (<32 weeks GA) recruited by the NICU of 2 specialized hospitals. The participating families will be divided into 3 groups: a reference group (i.e. full term infants and their parents, receiving care as usual), a control group (i.e. premature infants and their parents, receiving care as usual) and an intervention group (i.e. premature infants and their parents, receiving VIG). The data will be collected during the first six months after birth using observations of parent-infant interactions, questionnaires and semi-structured interviews. Primary outcomes are the quality of parental bonding and parent-infant interactive behaviour. Parental secondary outcomes are (posttraumatic) stress symptoms

  11. The Teacher and Town Planner as Facilitator.

    ERIC Educational Resources Information Center

    Peel, Deborah

    2000-01-01

    Discussion of theories of facilitation in teaching focuses on citizen participation and the role of the facilitator in town planning. Highlights include hierarchies of learning; student-centered learning; facilitating community participation; information technology skills and interpersonal skills; and a rationale for participation. (LRW)

  12. Evaluation of the Facilitated Communication Pilot

    ERIC Educational Resources Information Center

    Cooper-Martin, Elizabeth

    2014-01-01

    The Office of Special Education and Student Services asked the Office of Shared Accountability to evaluate the "Facilitated Communication Pilot." In facilitated communication (FC), people with communication impairments express themselves by typing with the aid of a communication partner, called a facilitator, who provides physical (and…

  13. Technologies and Techniques for Supporting Facilitated Video

    ERIC Educational Resources Information Center

    Linnell, Natalie

    2011-01-01

    Worldwide, demand for education of all kinds is increasing beyond the capacity to provide it. One approach that shows potential for addressing this demand is facilitated video. In facilitated video, an educator is recorded teaching, and that video is sent to a remote site where it is shown to students by a facilitator who creates interaction…

  14. Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

    PubMed Central

    Lin, Audrey; Hokugo, Akishige; Choi, Jae; Nishimura, Ichiro

    2010-01-01

    Wounds created in the oral cavity heal rapidly and leave minimal scarring. We have examined a role of a previously isolated cDNA from oral wounds encoding wound inducible transcript-3.0 (wit3.0), also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2). FGFR1OP2/wit3.0 was highly expressed in oral wound fibroblasts without noticeable up-regulation of α-smooth muscle actin. In silico analyses, denaturing and nondenaturing gel Western blot, and immunocytology together demonstrated that FGFR1OP2/wit3.0 were able to dimerize and oligomerize through coiled-coil structures and appeared to associate with cytoskeleton networks in oral wound fibroblasts. Overexpression of FGFR1OP2/wit3.0 increased the floating collagen gel contraction of naïve oral fibroblasts to the level of oral wound fibroblasts, which was in turn attenuated by small-interfering RNA knockdown. The FGFR1OP2/wit3.0 synthesis did not affect the expression of collagen I as well as procontractile peptides such as α-smooth muscle actin, and transforming growth factor-β1 had no effect on FGFR1OP2/wit3.0 expression. Fibroblastic cells derived from embryonic stem cells carrying FGFR1OP2/wit3.0 (+/−) mutation showed significant retardation in cell migration. Thus, we postulate that FGFR1OP2/wit3.0 may regulate cell motility and stimulate wound closure. FGFR1OP2/wit3.0 was not up-regulated during skin wound healing; however, when treated with FGFR1OP2/wit3.0 -expression vector, the skin wound closure was significantly accelerated, resulting in the limited granulation tissue formation. Our data suggest that FGFR1OP2/wit3.0 may possess a therapeutic potential for wound management. PMID:19959814

  15. TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase.

    PubMed

    Wang, Wei; Huang, Xuan; Xin, Hong-Bo; Fu, Mingui; Xue, Aimin; Wu, Zhao-Hui

    2015-05-22

    DNA damage-induced NF-κB activation plays a critical role in regulating cellular response to genotoxic stress. However, the molecular mechanisms controlling the magnitude and duration of this genotoxic NF-κB signaling cascade are poorly understood. We recently demonstrated that genotoxic NF-κB activation is regulated by reversible ubiquitination of several essential mediators involved in this signaling pathway. Here we show that TRAF family member-associated NF-κB activator (TANK) negatively regulates NF-κB activation by DNA damage via inhibiting ubiquitination of TRAF6. Despite the lack of a deubiquitination enzyme domain, TANK has been shown to negatively regulate the ubiquitination of TRAF proteins. We found TANK formed a complex with MCPIP1 (also known as ZC3H12A) and a deubiquitinase, USP10, which was essential for the USP10-dependent deubiquitination of TRAF6 and the resolution of genotoxic NF-κB activation upon DNA damage. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of TANK in human cells significantly enhanced NF-κB activation by genotoxic treatment, resulting in enhanced cell survival and increased inflammatory cytokine production. Furthermore, we found that the TANK-MCPIP1-USP10 complex also decreased TRAF6 ubiquitination in cells treated with IL-1β or LPS. In accordance, depletion of USP10 enhanced NF-κB activation induced by IL-1β or LPS. Collectively, our data demonstrate that TANK serves as an important negative regulator of NF-κB signaling cascades induced by genotoxic stress and IL-1R/Toll-like receptor stimulation in a manner dependent on MCPIP1/USP10-mediated TRAF6 deubiquitination.

  16. Facilitating Moderate Drinking on Campus.

    ERIC Educational Resources Information Center

    McBrien, Robert J.

    1980-01-01

    By identifying the environmental conditions associated with alcohol abuse and alcohol use in moderation, staff can help students develop effective strategies for change. Stimulus control methods are recommended as effective behavioral change strategies. (RC)

  17. Validation of a real-time PCR based method for detection of Clostridium botulinum types C, D and their mosaic variants C-D and D-C in a multicenter collaborative trial.

    PubMed

    Woudstra, Cedric; Skarin, Hanna; Anniballi, Fabrizio; Auricchio, Bruna; De Medici, Dario; Bano, Luca; Drigo, Ilenia; Hansen, Trine; Löfström, Charlotta; Hamidjaja, Raditijo; van Rotterdam, Bart J; Koene, Miriam; Bäyon-Auboyer, Marie-Hélène; Buffereau, Jean-Philippe; Fach, Patrick

    2013-08-01

    Two real-time PCR arrays based on the GeneDisc(®) cycler platform (Pall-GeneDisc Technologies) were evaluated in a multicenter collaborative trial for their capacity to specifically detect and discriminate Clostridium botulinum types C, D and their mosaic variants C-D and D-C that are associated with avian and mammalian botulism. The GeneDisc(®) arrays developed as part of the DG Home funded European project 'AnibioThreat' were highly sensitive and specific when tested on pure isolates and naturally contaminated samples (mostly clinical specimen from avian origin). Results of the multicenter collaborative trial involving eight laboratories in five European Countries (two laboratories in France, Italy and The Netherlands, one laboratory in Denmark and Sweden), using DNA extracts issued from 33 pure isolates and 48 naturally contaminated samples associated with animal botulism cases, demonstrated the robustness of these tests. Results showed a concordance among the eight laboratories of 99.4%-100% for both arrays. The reproducibility of the tests was high with a relative standard deviation ranging from 1.1% to 7.1%. Considering the high level of agreement achieved between the laboratories these PCR arrays constitute robust and suitable tools for rapid detection of C. botulinum types C, D and mosaic types C-D and D-C. These are the first tests for C. botulinum C and D that have been evaluated in a European multicenter collaborative trial.

  18. Tetanus in adults: results of the multicenter ID-IRI study.

    PubMed

    Tosun, S; Batirel, A; Oluk, A I; Aksoy, F; Puca, E; Bénézit, F; Ural, S; Nayman-Alpat, S; Yamazhan, T; Koksaldi-Motor, V; Tekin, R; Parlak, E; Tattevin, P; Kart-Yasar, K; Guner, R; Bastug, A; Meric-Koc, M; Oncu, S; Sagmak-Tartar, A; Denk, A; Pehlivanoglu, F; Sengoz, G; Sørensen, S M; Celebi, G; Baštáková, L; Gedik, H; Dirgen-Caylak, S; Esmaoglu, A; Erol, S; Cag, Y; Karagoz, E; Inan, A; Erdem, H

    2017-03-28

    Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

  19. Multi-Center Implementation of NPR 7123.1A: A Collaborative Effort

    NASA Technical Reports Server (NTRS)

    Hall, Phillip B.; McNelis, Nancy B.

    2011-01-01

    Collaboration efforts between MSFC and GRC Engineering Directorates to implement the NASA Systems Engineering (SE) Engine have expanded over the past year to include other NASA Centers. Sharing information on designing, developing, and deploying SE processes has sparked further interest based on the realization that there is relative consistency in implementing SE processes at the institutional level. This presentation will provide a status on the ongoing multi-center collaboration and provide insight into how these NPR 7123.1A SE-aligned directives are being implemented and managed to better support the needs of NASA programs and projects. NPR 7123.1A, NASA Systems Engineering Processes and Requirements, was released on March 26, 2007 to clearly articulate and establish the requirements on the implementing organization for performing, supporting, and evaluating SE activities. In early 2009, MSFC and GRC Engineering Directorates undertook a collaborative opportunity to share their research and work associated with developing, updating and revising their SE process policy to comply and align with NPR 7123.1A. The goal is to develop instructions, checklists, templates, and procedures for each of the 17 SE process requirements so that systems engineers will be a position to define work that is process-driven. Greater efficiency and more effective technical management will be achieved due to consistency and repeatability of SE process implementation across and throughout each of the NASA centers. An added benefit will be to encourage NASA centers to pursue and collaborate on joint projects as a result of using common or similar processes, methods, tools, and techniques.

  20. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma.

    PubMed

    Fehniger, Todd A; Larson, Sarah; Trinkaus, Kathryn; Siegel, Marilyn J; Cashen, Amanda F; Blum, Kristie A; Fenske, Timothy S; Hurd, David D; Goy, Andre; Schneider, Stephanie E; Keppel, Catherine R; Wagner-Johnston, Nina D; Carson, Kenneth R; Bartlett, Nancy L

    2011-11-10

    Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

  1. SALTO: a randomized, multicenter study assessing octreotide LAR in inoperable bowel obstruction.

    PubMed

    Laval, Guillemette; Rousselot, Hubert; Toussaint-Martel, Sophie; Mayer, Françoise; Terrebonne, Eric; François, Eric; Brixi, Hédia; Nguyen, Thierry; Bourdeix, Isabelle; Bisot-Locard, Ségolène; Zelek, Laurent

    2012-02-01

    This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was "success" at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

  2. Early-Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network (RCN) Study

    SciTech Connect

    Cai Ling; Stauder, Michael C.; Zhang Yujing; Poortmans, Philip; Li Yexiong; Constantinou, Nicolaos; Thariat, Juliette; Kadish, Sidney P.; Nguyen, Tan Dat; Kirova, Youlia M.; Ghadjar, Pirus; Weber, Damien C.; Bertran, Victoria Tuset; Ozsahin, Mahmut; Mirimanoff, Rene-Olivier

    2012-05-01

    Purpose: Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with Stages I and II PBL. Patients and Methods: Thirteen Rare Cancer Network (RCN) institutions enrolled 116 consecutive patients with PBL treated between 1987 and 2008 in this study. Eighty-seven patients underwent chemoradiotherapy (CXRT) without (78) or with (9) surgery, 15 radiotherapy (RT) without (13) or with (2) surgery, and 14 chemotherapy (CXT) without (9) or with (5) surgery. Median RT dose was 40 Gy (range, 4-60). The median number of CXT cycles was six (range, 2-8). Median follow-up was 41 months (range, 6-242). Results: The overall response rate at the end of treatment was 91% (complete response [CR] 74%, partial response [PR] 17%). Local recurrence or progression was observed in 12 (10%) patients and systemic recurrence in 17 (15%). The 5-year overall survival (OS), lymphoma-specific survival (LSS), and local control (LC) were 76%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for OS and LSS were International Prognostic Index (IPI) score {<=}1 (p = 0.009), high-grade histology (p = 0.04), CXRT (p = 0.05), CXT (p = 0.0004), CR (p < 0.0001), and RT dose >40 Gy (p = 0.005). For LC, only CR and Stage I were favorable factors. In multivariate analysis, IPI score, RT dose, CR, and CXT were independently influencing the outcome (OS and LSS). CR was the only predicting factor for LC. Conclusion: This large multicenter retrospective study confirms the good prognosis of early-stage PBL treated with combined CXRT. An adequate dose of RT and complete CXT regime were associated with better outcome.

  3. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  4. Uveitis in childhood-onset systemic lupus erythematosus patients: a multicenter survey.

    PubMed

    Kahwage, Paola Pinheiro; Ferriani, Mariana Paes Leme; Furtado, João M; de Carvalho, Luciana Martins; Pileggi, Gecilmara Salviato; Gomes, Francisco Hugo Rodrigues; Terreri, Maria Teresa; Magalhães, Claudia Saad; Pereira, Rosa Maria Rodrigues; Sacchetti, Silvana Brasilia; Marini, Roberto; Bonfá, Eloisa; Silva, Clovis Artur; Ferriani, Virgínia Paes Leme

    2017-03-01

    The aim of this study is to assess uveitis prevalence in a large cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. A retrospective multicenter cohort study including 852 cSLE patients was performed in ten pediatric rheumatology centers (Brazilian cSLE group). An investigator meeting was held and all participants received database training. Uveitis was diagnosed through clinical assessment by the uveitis expert ophthalmologist of each center. Patients with and without uveitis were assessed for lupus clinical/laboratory features and treatments. Uveitis was observed in 7/852 cSLE patients (0.8%). Two of them had ocular complications: cataract and irreversible blindness in one patient and retinal ischemia with subsequent neovascularization and unilateral blindness in another. Uveitis was identified within the first 6 months of cSLE diagnosis in 6/7 patients (86%). Comparison of a subgroup of cSLE patients with (n = 7) and without uveitis (n = 73) and similar length of disease duration showed that patients with uveitis had increased SLEDAI-2K score (19 vs. 6; p < 0.01). In addition, fever (71 vs. 12%; p < 0.01), lymphadenopathy (29 vs. 1.4%; p = 0.02), arthritis (43 vs. 7%; p = 0.02), and use of intravenous methylprednisolone (71 vs. 22%; p = 0.01) were higher in cSLE patients with uveitis, as compared to those without this manifestation, respectively. Presence of fever was significantly associated with uveitis, independently of SLEDAI scores or use of intravenous methylprednisolone pulses, as shown by adjusted regression analysis (adjusted prevalence ratio 35.7, 95% CI 2.4-519.6; p < 0.01). Uveitis was a rare and initial manifestation of active cSLE patients. Early recognition is essential due to the possibility of irreversible blindness.

  5. Satisfaction and expectations of patients with inflammatory bowel disease on biologic therapy: a multicenter study

    PubMed Central

    Guarini, Alessandra; Biagini, Silvia; Capaldi, Antonella; Carretto, Daniela; Angelis, Anna De; Iudice, Salvatore; Martino, Giuseppina; Marziali, Barbara; Mattiola, Roberta; Ongarelli, Cristina; Onidi, Francesca Maria; Prinzio, Manuela; Puthiavettil, Reetha; Sardi, Romina; Schiavoni, Elisa; Sinatora, Rita; Zullo, Angelo

    2017-01-01

    Background The satisfaction perceived by patients with chronic diseases affects clinical outcomes and healthcare costs. Some patients with inflammatory bowel disease (IBD) develop a more severe form requiring biologic therapy. We assessed the quality of care perceived by IBD patients in dedicated centers. Methods This prospective, cross-sectional, multicenter study enrolled consecutive IBD patients who underwent biologic therapy in the participating centers. The nurses directly involved in the management of these patients explained the rationale of the survey, provided a specific questionnaire (CACHE), and collected data. The CACHE included 31 items structured in 6 domains: staff care, clinician care, center facilities, patient information, accessibility, and patient support. Patients’ satisfaction score for each domain ranged from 0 to 100%. Results Sixteen different Italian centers participated and a total of 450 patients were enrolled (283 with Crohn’s disease and 167 with ulcerative colitis). The overall score was 82.2±19.6, satisfaction with the clinicians care scoring the highest (87.6±3.2) and the information provided to the patient scoring the lowest (70.7±7.9). More specifically, it emerged that 5.2-19.5% of patients were unsatisfied with: 1) the communication between the IBD medical team and primary care physicians; 2) information received about the disease or patients’ associations; and 3) the accessibility of the center. Conclusion Although our data revealed an acceptably high rate of global satisfaction among IBD patients receiving biologic therapy, more effort should be made to improve patient information and communication between IBD teams, other specialists and primary care physicians. PMID:28042244

  6. Prospective, multicenter evaluation of balloon sinus dilation for treatment of pediatric chronic rhinosinusitis

    PubMed Central

    Rosenbloom, Jeffrey S.; Skarada, Douglas; Gutman, Michael; Hoy, Mark J.; Nguyen, Shaun A.

    2016-01-01

    Background Although balloon sinus dilation is a treatment option for adults with chronic rhinosinusitis (CRS), there have been few studies performed in pediatric patients. Methods This study was designed as a prospective, multicenter, single‐arm investigation. Children (2 to 21 years old) with CRS who had failed medical management were treated with balloon sinus dilation and followed to 6 months postprocedure. Results Fifty children were treated at 4 centers; 33 participants were 2 to 12 years old (mean ± standard deviation age: 6.6 ± 2.2 years) and 17 participants were >12 to 21 years (mean age: 15.7 ± 2.5 years). A total of 157 sinus dilations were attempted (98 maxillary, 30 frontal, and 29 sphenoid sinuses) and all were successful with no complications. Significant improvement in the Sinus and Nasal Quality of Life Survey (SN‐5) was seen for all children between baseline and 6 months (4.6 ± 1.2 vs 1.7 ± 0.8; p < 0.0001) and 92% improved by a minimal clinically important difference (MCID) of 1.0 or more. Those children aged 2 to 12 years with standalone balloon dilation also showed significant SN‐5 improvements between baseline and follow‐up (4.5 ± 1.0 vs 1.9 ± 0.8; p < 0.0001). Multivariate regression analysis showed no differences or associations of SN‐5 improvement at 6 months with the presence of allergy, asthma, or concomitant procedures. For adolescents, overall 22‐item Sino‐Nasal Outcome Test (SNOT‐22) mean scores were also significantly improved at 6 months (42.2 ± 19.2 vs 10.4 ± 9.7; p < 0.0001). Conclusion Balloon sinus dilation is safe and appears effective for children with CRS aged 2 years and older. PMID:27888649

  7. Acceptance of living liver donation among medical students: A multicenter stratified study from Spain

    PubMed Central

    Ríos, Antonio; López-Navas, Ana Isabel; López-López, Ana Isabel; Gómez, Francisco Javier; Iriarte, Jorge; Herruzo, Rafael; Blanco, Gerardo; Llorca, Francisco Javier; Asunsolo, Angel; Sánchez-Gallegos, Pilar; Gutiérrez, Pedro Ramón; Fernández, Ana; de Jesús, María Teresa; Martínez-Alarcón, Laura; Lana, Alberto; Fuentes, Lorena; Hernández, Juan Ramón; Virseda, Julio; Yelamos, José; Bondía, José Antonio; Hernández, Antonio Miguel; Ayala, Marco Antonio; Ramírez, Pablo; Parrilla, Pascual

    2016-01-01

    AIM: To analyze the attitude of Spanish medical students toward living liver donation (LLD) and to establish which factors have an influence on this attitude. METHODS: Study type: A sociological, interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain (n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire (PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student´s t test, χ2 test and logistic regression analysis. RESULTS: The completion rate was 95.7% (n = 9275). 89% (n = 8258) were in favor of related LLD, and 32% (n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude: (1) age (P = 0.008); (2) sex (P < 0.001); (3) academic year (P < 0.001); (4) geographical area (P = 0.013); (5) believing in the possibility of needing a transplant oneself in the future (P < 0.001); (6) attitude toward deceased donation (P < 0.001); (7) attitude toward living kidney donation (P < 0.001); (8) acceptance of a donated liver segment from a family member if one were needed (P < 0.001); (9) having discussed the subject with one's family (P < 0.001) and friends (P < 0.001); (10) a partner's opinion about the subject (P < 0.001); (11) carrying out activities of an altruistic nature; and (12) fear of the possible mutilation of the body after donation (P < 0.001). CONCLUSION: Spanish medical students have a favorable attitude toward LLD. PMID:27433093

  8. Practice Patterns Regarding Management of Rectovaginal Fistulae: A Multicenter Review From the Fellows’ Pelvic Research Network

    PubMed Central

    Oakley, Susan H.; Brown, Heidi W.; Yurteri-Kaplan, Ladin; Greer, Joy A.; Richardson, Monica L.; Adelowo, Amos; Lindo, Fiona M.; Greene, Kristie A.; Fok, Cynthia S.; Book, Nicole M.; Saiz, Cristina M.; Plowright, Leon N.; Harvie, Heidi S.; Pauls, Rachel N.

    2016-01-01

    Objectives Rectovaginal fistulae (RVFs) are often debilitating and there are no established treatment algorithms. We sought to describe current diagnosis and management strategies for RVFs across the United States. Methods This institutional review board–approved multicenter retrospective study included 12 sites. Cases were identified using International Classification of Diseases, Ninth Revision codes during a 5-year period. Demographics, management, and outcomes of RVF treatment were collected. Results Three hundred forty-two charts were identified; 176 (52%) met criteria for inclusion. The mean (SD) age was 45 (17) years. Medical history included hypertension (21%), cancer (17%), Crohn disease (11%), and diabetes (7%). Rectovaginal fistulae were often associated with obstetric trauma (42%), infection/inflammation (24%), and cancer (11%). Overall, most RVFs were primary (94%), small (0.5–1.5 cm; 49%), transsphincteric (31%), and diagnosed via vaginal and rectal (60%) examination. Eighteen percent (32/176) were initially managed conservatively for a median duration of 56 days (interquartile range, 29–168) and 66% (21/32) of these resolved. Almost half (45%) of RVFs treated expectantly were tiny (<0.5 cm). Eighty-two percent (144/176) of subjects were initially managed surgically and 81% (117/144) resolved. Procedures included simple fistulectomy with or without Martius graft (59%), transsphincteric repair (23%), transverse transperineal repair (10%), and open techniques (8%), and 87% of these procedures were performed by urogynecologists. Conclusions In this large retrospective review, most primary RVFs were treated surgically, with a success rate of more than 80%. Two thirds of RVFs managed conservatively resolved spontaneously, and most of these were tiny (<0.5 cm). These success rates can be used in counseling to help our patients make informed decisions about their treatment options. PMID:25730438

  9. Multicenter Closed-Loop/Hybrid Meal Bolus Insulin Delivery with Type 1 Diabetes

    PubMed Central

    Chase, H. Peter; Doyle, Francis J.; Zisser, Howard; Renard, Eric; Nimri, Revital; Cobelli, Claudio; Buckingham, Bruce A.; Maahs, David M.; Anderson, Stacey; Magni, Lalo; Lum, John; Calhoun, Peter; Kollman, Craig

    2014-01-01

    Abstract Background: This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system. Subjects and Methods: This study was a multicenter trial in 53 patients, 12–65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4. Results: Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period). Conclusions: The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm. PMID:25188375

  10. Prospective Multicenter Study of the Impact of Carbapenem Resistance on Mortality in Pseudomonas aeruginosa Bloodstream Infections

    PubMed Central

    Suarez, Cristina; Gozalo, Mónica; Murillas, Javier; Almirante, Benito; Pomar, Virginia; Aguilar, Manuela; Granados, Ana; Calbo, Esther; Rodríguez-Baño, Jesús; Rodríguez, Fernando; Tubau, Fe; Martínez-Martínez, Luis; Oliver, Antonio

    2012-01-01

    The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities. PMID:22155832

  11. A Multicenter, Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

    PubMed Central

    Cerritelli, Francesco; Pizzolorusso, Gianfranco; Renzetti, Cinzia; Cozzolino, Vincenzo; D’Orazio, Marianna; Lupacchini, Mariacristina; Marinelli, Benedetta; Accorsi, Alessandro; Lucci, Chiara; Lancellotti, Jenny; Ballabio, Silvia; Castelli, Carola; Molteni, Daniela; Besana, Roberto; Tubaldi, Lucia; Perri, Francesco Paolo; Fusilli, Paola; D’Incecco, Carmine; Barlafante, Gina

    2015-01-01

    Background Despite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes. Materials and Methods The present multi-center randomized single blind parallel group clinical trial enrolled newborns who met the criteria for gestational age between 29 and 37 weeks, without any congenital complication from 3 different public neonatal intensive care units. Preterm infants were randomly assigned to usual prenatal care (control group) or osteopathic manipulative treatment (study group). The primary outcome was the mean difference in length of hospital stay between groups. Results A total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention. Conclusions Osteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. PMID:25974071

  12. International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation.

    PubMed

    Ding, Dale; Starke, Robert M; Kano, Hideyuki; Mathieu, David; Huang, Paul P; Feliciano, Caleb; Rodriguez-Mercado, Rafael; Almodovar, Luis; Grills, Inga S; Silva, Danilo; Abbassy, Mahmoud; Missios, Symeon; Kondziolka, Douglas; Barnett, Gene H; Dade Lunsford, L; Sheehan, Jason P

    2017-02-01

    OBJECTIVE Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients. METHODS The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs. RESULTS A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001). CONCLUSIONS Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

  13. Cognitive-behavioral screening reveals prevalent impairment in a large multicenter ALS cohort

    PubMed Central

    Factor-Litvak, Pam; Goetz, Raymond; Lomen-Hoerth, Catherine; Nagy, Peter L.; Hupf, Jonathan; Singleton, Jessica; Woolley, Susan; Andrews, Howard; Heitzman, Daragh; Bedlack, Richard S.; Katz, Jonathan S.; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Björn; Fernandes Filho, J. Americo M.; Kasarskis, Edward J.; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Koczon-Jaremko, Boguslawa A.; Mitsumoto, Hiroshi

    2016-01-01

    Objectives: To characterize the prevalence of cognitive and behavioral symptoms using a cognitive/behavioral screening battery in a large prospective multicenter study of amyotrophic lateral sclerosis (ALS). Methods: Two hundred seventy-four patients with ALS completed 2 validated cognitive screening tests and 2 validated behavioral interviews with accompanying caregivers. We examined the associations between cognitive and behavioral performance, demographic and clinical data, and C9orf72 mutation data. Results: Based on the ALS Cognitive Behavioral Screen cognitive score, 6.5% of the sample scored below the cutoff score for frontotemporal lobar dementia, 54.2% scored in a range consistent with ALS with mild cognitive impairment, and 39.2% scored in the normal range. The ALS Cognitive Behavioral Screen behavioral subscale identified 16.5% of the sample scoring below the dementia cutoff score, with an additional 14.1% scoring in the ALS behavioral impairment range, and 69.4% scoring in the normal range. Conclusions: This investigation revealed high levels of cognitive and behavioral impairment in patients with ALS within 18 months of symptom onset, comparable to prior investigations. This investigation illustrates the successful use and scientific value of adding a cognitive-behavioral screening tool in studies of motor neuron diseases, to provide neurologists with an efficient method to measure these common deficits and to understand how they relate to key clinical variables, when extensive neuropsychological examinations are unavailable. These tools, developed specifically for patients with motor impairment, may be particularly useful in patient populations with multiple sclerosis and Parkinson disease, who are known to have comorbid cognitive decline. PMID:26802094

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

    PubMed

    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 < 0.01) during the first year of residency, and the prevalence of 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.

  15. Perceived Fear Appeals and Examination Performance: Facilitating or Debilitating Outcomes?

    ERIC Educational Resources Information Center

    Putwain, Dave; Symes, Wendy

    2011-01-01

    This study examines whether students' perception of classroom fear appeals concerning a forthcoming high-stakes examination are associated with facilitating or debilitating performance outcomes. Self-report data were collected for perceived fear appeals, test anxiety and achievement goals from a sample of 273 students in their final year of…

  16. Facilitators of and Barriers to Model School Psychological Services

    ERIC Educational Resources Information Center

    Castillo, Jose M.; Arroyo-Plaza, Javier; Tan, Sim Yin; Sabnis, Sujay; Mattison, Amira

    2017-01-01

    This study examined facilitators of and barriers to comprehensive and integrated services. A national sample of 267 full-time practicing school psychologists who were Regular Members or Early Career Members of the National Association of School Psychologists participated. We administered a survey to participants that measured the extent to which…

  17. Management of Pneumothorax in Emergency Medicine Departments: Multicenter Trial

    PubMed Central

    Ince, Abdulkadir; Ozucelik, Dogac Niyazi; Avci, Akkan; Nizam, Ozgur; Dogan, Halil; Topal, Mehmet Ali

    2013-01-01

    Background: Pneumothorax is common and life-threatening clinical condition which may require emergency treatment in Emergency Medicine Departments. Objectives: We aimed to reveal the epidemiological analysis of the patients admitted to the Emergency Department with pneumothorax. Material and Methods: This case-control and multi-center study was conducted in the patients treated with the diagnosis of pneumothorax between 01.01.2010-31.12.2010. Patient data were collected from hospital automation system. According to the etiology of the pneumothorax, study groups were arranged like spontaneous pneumothorax and traumatic pneumothorax. Results: 82.2% (n = 106) of patients were male and 17.8% (n = 23) of patients were female and mean age were 31.3 ± 20,2 (Minimum: 1, Maximum: 87). 68.2% (n = 88) of patients were spontaneous pneumothorax (61.36%, n=79 were primary spontaneous pneumothorax) and 31.8% (n = 41) of patients were traumatic pneumothorax (21.95% were iatrogenic pneumothorax). Main complaint is shortness of breath (52.3%, n=67) and 38% (n=49) of patients were smokers. Posteroanterior (PA) Chest X-Ray has been enough for 64.3% (n = 83) of the patients' diagnosis. Tube thoracostomy is applied to 84.5% (n = 109) of patients and surgery is applied to 9.3% (n = 12) of patients and 6.2% (n = 8) of patients were discharged with conservative treatment. Spontaneous pneumothorax showed statistically significant high recurrence compared with traumatic pneumothorax (P = 0.007). 4.65% of (n = 6) patients died. The average age of those who died (9.3 ± 19.9), statistically were significantly lower the mean age of living patients (32.4 ± 19.7) (t test, P = 0,006). 83.33% of the patients who died were neonatals and in the 0-1 years age group, and five of these patients were secondary spontaneous pneumothorax, and one of these patients were iatrogenic pneumothorax due to mechanical ventilation. Conclusions: Pneumothorax in adults can be treated by tube thoracostomy or

  18. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  19. [Use of amantadine sulfate (PK-MERZ) during emergence from coma: results of a multicenter study].

    PubMed

    Belkin, A A; Shchegolev, A V; Kondrat'ev, A N; Bubnova, I D

    2008-01-01

    The paper gives the results of the first multicenter study of the efficiency of using amantadine sulfate (PK-Merz) in patients with acute cerebral disease during coma emergence. The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease. Full objectivism of the findings requires further studies.

  20. Holmium:YAG laser coronary angioplasty: results of a multicenter registry

    NASA Astrophysics Data System (ADS)

    Topaz, On

    1994-07-01

    To date, 1201 symptomatic patients with significant coronary artery disease were treated with the mid IR holmium:YAG (2.1 micron) laser in a multicenter study. Updated results of this study, as presented herein, substantiate the important role of this laser in treatment of lesions not ideal for conventional balloon angioplasty. This device is a safe and effective means of coronary revascularization.

  1. Enhanced Pair Production in Multicenter Systems by SuperIntense Lasers

    NASA Astrophysics Data System (ADS)

    Bandrauk, Andre

    2014-03-01

    Electron-positron(e-e +) pair production is considered for many-center systems with multiple bare nuclei immersed in intense static electric fields corresponding to the extrema of electric fields planned by future super intense laser pulse sources with intensities I > 1024 W/cm2. It is shown analytically using an exactly solvable 1-D delta potential model in a multicenter Dirac equation that there are two distinct regimes where pair production rates are enhanced.At small internuclear distances, the effective nuclear charge approaches the critical charge where the ground state dives into the negative continuum of the Dirac equation. At large atomic distances a new mechanism is predicted, similar to Charge Resonance Enhanced Ionization of molecules by intense, I ~ 1024 W/cm2, laser pulses. Multicenter resonances from the negative energy states are shown to cross into the positive energy states due to large field induced Stark shifts thus resulting in a resonantly enhanced pair production mechanism. A numerical method is developed to calculate the pair production rates from the multicenter Dirac equation. The latter is evaluated for systems (clusters) up to five nuclei of large charge. It is shown that the pair production rate for multicenter systems in superintense electric fields generally exceeds by orders of magnitudes the Schwinger tunneling rate which requires intensities of ~ 1029 W''/cm2. Funded by Canada Research Chair Program.

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

    ERIC Educational Resources Information Center

    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…

  3. MULTI-CENTER PRECISION OF CORTICAL AND TRABECULAR BONE QUALITY MEASURES ASSESSED BY HR-PQCT

    PubMed Central

    Burghardt, Andrew J.; Pialat, Jean-Baptiste; Kazakia, Galateia J.; Boutroy, Stephanie; Engelke, Klaus; Patsch, Janina M.; Valentinitsch, Alexander; Liu, Danmei; Szabo, Eva; Bogado, Cesar E.; Zanchetta, Maria Belen; McKay, Heather A.; Shane, Elizabeth; Boyd, Steven K.; Bouxsein, Mary L.; Chapurlat, Roland; Khosla, Sundeep; Majumdar, Sharmila

    2012-01-01

    High-resolution peripheral quantitative computed tomography (HR-pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technique to address important skeletal health questions requires translation to standardized multi-center data pools. Our goal was to evaluate the feasibility of pooling data in multi-center HR-pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition-realistic phantoms constructed from cadaveric radii. Single-center precision was determined by repeat scanning over short (<72hrs), intermediate (3–5mo), and long-term intervals (28mo). Multi-center precision was determined by imaging the phantoms at nine different HR-pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single-center short-term RMSCVs were <1% for all parameters except Ct.Th (1.1%), Ct.Th.SD (2.6%), Tb.Sp.SD (1.8%), and porosity measures (6–8%). Intermediate-term RMSCVs were generally not statistically different from short-term values. Long-term variability was significantly greater for all density measures (0.7–2.0%; p < 0.05 vs. short-term) and several structure measures: Ct.Th (3.4%; p < 0.01 vs. short-term), Ct.Po (15.4%; p < 0.01 vs. short-term), and Tb.Th (2.2%; p < 0.01 vs. short-term). Multi-center RMSCVs were also significantly higher than short-term values: 2–4% for density and µFE measures (p < 0.0001), 2.6–5.3% for morphometric measures (p < 0.001), while Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multi-center precision errors for HR-pQCT parameters were generally less than 5%. Phantom-based multi-center precision was comparable to previously reported in vivo single-center precision errors, although this was approximately 2–5 times worse than ex vivo short

  4. Acceptability of emergency contraception in Brazil, Chile, and Mexico. 2 - Facilitating factors versus obstacles.

    PubMed

    Díaz, Soledad; Hardy, Ellen; Alvarado, Gloria; Ezcurra, Enrique

    2003-01-01

    A multi-center study was performed in Brazil, Chile, and Mexico to identify factors that may facilitate or hinder the introduction of emergency contraception (EC) as well as perceptions concerning emergency contraceptive pills. Background information on the socio-cultural, political, and legal context and the characteristics of reproductive health services was collected. The opinions of potential users and providers were obtained through discussion groups, and those of authorities and policymakers through semi-structured interviews. Barriers to introduction included: perception of EC as an abortifacient, opposition by the Catholic Church, limited recognition of sexual and reproductive rights, limited sex education, and insensitivity to gender issues. Facilitating factors were: perception of EC as a method that would prevent abortion and pregnancy among adolescents and rape victims; interest in the method shown by potential users as well as by some providers and authorities. It appears possible to reduce barriers through support from segments of society committed to improving sexual and reproductive health and adequate training of health care providers.

  5. How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study

    PubMed Central

    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; Burucoa, Christophe

    2015-01-01

    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. PMID:26637380

  6. How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study.

    PubMed

    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.

  7. The Development of the Multi-Center Traffic Management Advisor (MCTMA): Traffic Flow Management Research in a Multi-Facility Environment

    NASA Technical Reports Server (NTRS)

    Lee, Katharine K.; Davis, Thomas J.; Levin, Kerry M.; Rowe, Dennis W.

    2001-01-01

    The Traffic Management Advisor (TMA) is a decision-support tool for traffic managers and air traffic controllers that provides traffic flow visualization and other flow management tools. TMA creates an efficiently sequenced and safely spaced schedule for arrival traffic that meets but does not exceed specified airspace system constraints. TMA is being deployed at selected facilities throughout the National Airspace System in the US as part of the FAA's Free Flight Phase 1 program. TMA development and testing, and its current deployment, focuses on managing the arrival capacity for single major airports within single terminal areas and single en route centers. The next phase of development for this technology is the expansion of the TMA capability to complex facilities in which a terminal area or airport is fed by multiple en route centers, thus creating a multicenter TMA functionality. The focus of the multi-center TMA (McTMA) development is on the busy facilities in the Northeast comdor of the US. This paper describes the planning and development of McTMA and the challenges associated with adapting a successful traffic flow management tool for a very complex airspace.

  8. Facilitation techniques as predictors of crew participation in LOFT debriefings

    NASA Technical Reports Server (NTRS)

    McDonnell, L. K.

    1996-01-01

    Based on theories of adult learning and airline industry guidelines for Crew Resource Management (CRM), the stated objective during Line Oriented Flight Training (LOFT) debriefings is for instructor pilots (IP's) to facilitate crew self-analysis of performance. This study reviews 19 LOFT debriefings from two major U.S. airlines to examine the relationship between IP efforts at facilitation and associated characteristics of crew participation. A subjective rating scale called the Debriefing Assessment Battery was developed and utilized to evaluate the effectiveness of IP facilitation and the quality of crew participation. The results indicate that IP content, encouragement, and questioning techniques are highly and significantly correlated with, and can therefore predict, the degree and depth of crew participation.

  9. Simple scale interpolator facilitates reading of graphs

    NASA Technical Reports Server (NTRS)

    Fetterman, D. E., Jr.

    1965-01-01

    Simple transparent overlay with interpolation scale facilitates accurate, rapid reading of graph coordinate points. This device can be used for enlarging drawings and locating points on perspective drawings.

  10. Lurasidone for the Treatment of Irritability Associated with Autistic Disorder

    ERIC Educational Resources Information Center

    Loebel, Antony; Brams, Matthew; Goldman, Robert S.; Silva, Robert; Hernandez, David; Deng, Ling; Mankoski, Raymond; Findling, Robert L.

    2016-01-01

    The aim of this study was to evaluate the short-term efficacy and safety of lurasidone in treating irritability associated with autistic disorder. In this multicenter trial, outpatients age 6-17 years who met DSM-IV-TR criteria for autistic disorder, and who demonstrated irritability, agitation, and/or self-injurious behaviors were randomized to…

  11. Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study

    PubMed Central

    Suárez, Berta; López-Abente, Gonzalo; Martínez, Carmen; Navarro, Carmen; Tormo, Maria José; Rosso, Stefano; Schraub, Simon; Gafà, Lorenzo; Sancho-Garnier, Hélène; Wechsler, Janine; Zanetti, Roberto

    2007-01-01

    Background Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type. Methods We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models. Results For NMSC as a whole (both histological types), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of SCC (though not of BCC) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78). Conclusion Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent

  12. BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study.

    PubMed

    Tallini, Giovanni; de Biase, Dario; Durante, Cosimo; Acquaviva, Giorgia; Bisceglia, Michele; Bruno, Rocco; Bacchi Reggiani, Maria Letizia; Casadei, Gian Piero; Costante, Giuseppe; Cremonini, Nadia; Lamartina, Livia; Meringolo, Domenico; Nardi, Francesco; Pession, Annalisa; Rhoden, Kerry J; Ronga, Giuseppe; Torlontano, Massimo; Verrienti, Antonella; Visani, Michela; Filetti, Sebastiano

    2015-10-01

    Studies from single institutions have analyzed BRAF in papillary microcarcinomas, sometimes with contradictory results. Most of them have provided limited integration of histological and clinical data. To obtain a comprehensive picture of BRAF V600E-mutated microcarcinomas and to evaluate the role of BRAF testing in risk stratification we performed a retrospective multicenter analysis integrating microscopical, pathological, and clinical information. Three hundred and sixty-five samples from 300 patients treated at six medical institutions covering different geographical regions of Italy were analyzed with central review of all cases. BRAF V600E statistical analysis was conducted on 298 microcarcinomas from 264 patients after exclusion of those that did not meet the required criteria. BRAF V600E was identified in 145/298 tumors (49%) including the following subtypes: 35/37 (95%, P<0.0001) tall cell and 72/114 (64%, P<0.0001) classic; conversely 94/129 follicular variant papillary microcarcinomas (73%, P<0.0001) were BRAF wild type. BRAF V600E-mutated microcarcinomas were characterized by markedly infiltrative contours (P<0.0001) with elongated strings of neoplastic cells departing from the tumor, and by intraglandular tumor spread (P<0.0001), typically within 5 mm of the tumor border. Multivariate analysis correlated BRAF V600E with specific microscopic features (nuclear grooves, optically clear nuclei, tall cells within the tumor, and tumor fibrosis), aggressive growth pattern (infiltrative tumor border, extension into extrathyroidal tissues, and intraglandular tumor spread), higher American Thyroid Association recurrence risk group, and non-incidental tumor discovery. The following showed the strongest link to BRAF V600E: tall cell subtype, many neoplastic cells with nuclear grooves or with optically clear nuclei, infiltrative growth, intraglandular tumor spread, and a tumor discovery that was non-incidental. BRAF V600E-mutated microcarcinomas represent a

  13. Multicenter study on the asymmetry of skin temperature in complex regional pain syndrome

    PubMed Central

    Cho, Chan Woo; Nahm, Francis Sahngun; Choi, Eunjoo; Lee, Pyung-Bok; Jang, In-Ki; Lee, Chul Joong; Kim, Yong Chul; Lee, Sang Chul

    2016-01-01

    Abstract According to the International Association for the Study of Pain (IASP) and American Medical Association (AMA), the diagnostic criteria for complex regional pain syndrome (CRPS) require the presence of skin temperature asymmetry. In CRPS, it is generally accepted that the temperature of skin of affected limbs changes from warm to cold; however, in our clinical practice, we have experienced many cases with different thermographic characteristics. Therefore, we conducted a retrospective multicenter study that examined the distribution of skin temperature in patients with CRPS and skin temperature asymmetry versus symptom duration. Patients diagnosed with type 1 or 2 CRPS were recruited. After confirming CRPS according to the IASP diagnostic criteria, infrared thermographic images were evaluated for skin temperature differences (ΔT) between the affected and unaffected limbs. A total of 296 patients with CRPS were included in this study. The median duration of symptoms was 6 months and the mean ± standard deviation of ΔT was –0.72 ± 1.65°C. A skin temperature difference between bilateral limbs (|ΔT|) of 1°C or less was seen in 131 patients (44.3%); thus, these 131 patients did not meet the IASP criteria for CRPS. Further, cool skin temperature was not observed in 88 patients (29.7%), meaning that these patients did not meet the AMA criteria for CRPS. There was no correlation between the symptom duration and ΔT (Spearman's rho = –0.075, P = 0.196) and there was no significant difference in the average ΔT among the 4 symptom duration groups (0–3 months, 4–6 months, 7–12 months, >12 months, P = 0.08). In conclusion, a considerable proportion of the patients that participated in this study did not meet the thermal criteria set forth by the IASP and AMA. Further, there was no correlation between symptom duration and skin temperature difference. PMID:28033251

  14. Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls

    PubMed Central

    Invernizzi, Pietro; Selmi, Carlo; Poli, Francesca; Frison, Sara; Floreani, Annarosa; Alvaro, Domenico; Almasio, Piero; Rosina, Floriano; Marzioni, Marco; Fabris, Luca; Muratori, Luigi; Qi, Lihong; Seldin, Michael F.; Gershwin, M. Eric; Podda, Mauro

    2008-01-01

    Genetic factors are critical in determining susceptibility to primary biliary cirrhosis (PBC), but there has not been a clear association with human leukocyte antigen (HLA) genes. We performed a multi-center case-control study and analyzed HLA class II DRB1 associations using a large cohort of 664 well-defined cases of PBC and 1,992 controls of Italian ancestry. Importantly, healthy controls were rigorously matched not only by age and gender, but also for the geographical origin of the proband four grandparents (Northern, Central, and Southern Italy). Following correction for multiple testing, DRB1*08 (Odds Ratio–OR, 3.3; 95% Confidence Interval–CI, 2.4−4.5) and DRB1*02 (OR 0.9; 95% CI 0.8−1.2) were significantly associated with PBC while alleles DRB1*11 (OR 0.4; 95% CI 0.3−0.4) and DRB1*13 (OR 0.7; 95% CI 0.6−0.9) were protective. When subjects were stratified according to their grandparental geographical origin, only the associations with DRB1*08 and DRB1*11 were common to all three areas. Associated DRB1 alleles were found only in a minority of patients while an additive genetic model is supported by the gene dosage effect for DRB1*11 allele and the interaction of DRB1*11,*13, and *08. Lastly, no significant associations were detected between specific DRB1 alleles and relevant clinical features represented by the presence of cirrhosis or serum autoantibodies. In conclusion, we confirm the role for HLA to determine PBC susceptibility and suggest that the effect of HLA is limited to patient subgroups. We suggest that a large whole-genome approach is required to identify further genetic elements contributing to the loss of tolerance in this disease. PMID:19003916

  15. Ultra-Early Combination Antiplatelet Therapy with Cilostazol for the Prevention of Branch Atheromatous Disease: A Multicenter Prospective Study

    PubMed Central

    Kimura, Teruo; Tucker, Adam; Sugimura, Toshihide; Seki, Toshitaka; Fukuda, Shin; Takeuchi, Satoru; Miyata, Shiro; Fujita, Tsutomu; Hashizume, Akira; Izumi, Naoto; Kawasaki, Kazutsune; Katsuno, Makoto; Hashimoto, Masaaki; Sako, Kazuhiro

    2016-01-01

    Background and Purpose The optimal use of antiplatelet therapy for intracranial branch atheromatous disease (BAD) is not known. Methods We conducted a prospective multicenter, single-group trial of 144 consecutive patients diagnosed with probable BAD. All patients were treated within 12 h of symptom onset to prevent clinical progression using dual antiplatelet therapy with cilostazol plus one oral antiplatelet drug (aspirin or clopidogrel). Endpoints of progressive BAD in the dual therapy group at 2 weeks were compared with a matched historical control group of 142 patients treated with single oral antiplatelet therapy using either cilostazol, aspirin, or clopidogrel. Results Progressive motor paresis occurred in 14 patients (9.7%) in the aggressive antiplatelet group, compared with 48 (33.8%) in the matched single antiplatelet group. Multivariate logistic regression analysis revealed the following variables to be associated with a better prognosis for BAD: baseline modified Rankin Scale score, dual oral antiplatelet therapy with cilostazol, and dyslipidemia (odds ratios of 0.616, 0.445, and 0.297, respectively). Hypertension was associated with a worse prognosis for BAD (odds ratio of 1.955). Conclusions Our trial showed that clinical progression of BAD was significantly reduced with the administration of ultra-early aggressive combination therapy using cilostazol compared to treatment with antiplatelet monotherapy. PMID:27728903

  16. REFLEX, a social-cognitive group treatment to improve insight in schizophrenia: study protocol of a multi-center RCT

    PubMed Central

    2011-01-01

    Background Insight is impaired in a majority of people with schizophrenia. Impaired insight is associated with poorer outcomes of the disorder. Based on existing literature, we developed a model that explains which processes may possibly play a role in impaired insight. This model was the starting point of the development of REFLEX: a brief psychosocial intervention to improve insight in schizophrenia. REFLEX is a 12-sessions group training, consisting of three modules of four sessions each. Modules in this intervention are: "coping with stigma", "you and your personal narrative", and "you in the present". Methods/Design REFLEX is currently evaluated in a multicenter randomized controlled trial. Eight mental health institutions in the Netherlands participate in this evaluation. Patients are randomly assigned to either REFLEX or an active control condition, existing of cognitive remediation exercises in a group. In a subgroup of patients, fMRI scans are made before and after training in order to assess potential haemodynamic changes associated with the effects of the training. Discussion REFLEX is one of the few interventions aiming specifically to improving insight in schizophrenia and has potential value for improving insight. Targeting insight in schizophrenia is a complex task, that comes with several methodological issues. These issues are addressed in the discussion of this paper. Trial registration Current Controlled Trials: ISRCTN50247539 PMID:21975132

  17. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study.

    PubMed

    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% (p<0.05), without differences in the associated treatments. The univariate analysis showed that the previous intrauterine deaths and higher hydroxychloroquine 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 (p<0.05). Our study shows the benefit of hydroxychloroquine addition in patients with refractory obstetrical APS and raises the need of prospective studies to confirm our preliminary study.

  18. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.

    PubMed

    Barone, Paolo; Antonini, Angelo; Colosimo, Carlo; Marconi, Roberto; Morgante, Letterio; Avarello, Tania P; Bottacchi, Eugenio; Cannas, Antonino; Ceravolo, Gabriella; Ceravolo, Roberto; Cicarelli, Giulio; Gaglio, Roberto M; Giglia, Rosa M; Iemolo, Francesco; Manfredi, Michela; Meco, Giuseppe; Nicoletti, Alessandra; Pederzoli, Massimo; Petrone, Alfredo; Pisani, Antonio; Pontieri, Francesco E; Quatrale, Rocco; Ramat, Silvia; Scala, Rosanna; Volpe, Giuseppe; Zappulla, Salvatore; Bentivoglio, Anna Rita; Stocchi, Fabrizio; Trianni, Giorgio; Dotto, Paolo Del

    2009-08-15

    We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.

  19. Trends and Predictors of Cigarette Smoking Among HIV Seropositive and Seronegative Men: The Multicenter AIDS Cohort Study

    PubMed Central

    Akhtar-Khaleel, Wajiha Z; Cook, Robert L.; Shoptaw, Steve; Surkan, Pamela J.; Teplin, Linda A; Stall, Ronald; Beyth, Rebecca J.; Plankey, Michael

    2016-01-01

    We measured the trend of cigarette smoking among HIV-seropositive and seronegative men over time from 1984-2012. Additionally, we examined the demographic correlates of smoking and smoking consumption. 6,577 men who have sex with men (MSM) from the Multicenter AIDS Cohort Study (MACS) were asked detailed information about their smoking history since their visit. Prevalence of smoking and quantity smoked was calculated yearly from 1984-2012. Poisson regression with robust error variance was used to estimate prevalence ratios of smoking in univariate and multivariate models. In 2012, 11.8% and 36.9% of men who were enrolled in the MACS before 2001 or during or after 2001 smoked cigarettes, respectively. In the multivariate analysis, black, non-Hispanic, lower education, enrollment wave, alcohol use, and marijuana use were positively associated with current smoking in MSM. HIV serostatus was not significant in the multivariate analysis. However, HIV variables, such as detectable viral load, were positively associated. Though cigarette smoking has declined over time, the prevalence still remains high among subgroups. There is still a need for tailored smoking cessation programs to decrease the risk of smoking in HIV-seropositive men who have sex with men. PMID:26093780

  20. Complications of Cardiac Perforation and Lead Dislodgement with an MRI-Conditional Pacing Lead: a Korean Multi-Center Experience

    PubMed Central

    2016-01-01

    Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis, MN, USA) has been reported to be associated with increased cardiac perforation and lead dislodgement. This study aimed to compare the incidence of cardiac perforation and lead dislodgement within 30 days after pacemaker implantation between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing lead. This was a nationwide, multicenter retrospective study in which we compared the incidence of adverse events between 277 patients implanted with 5086 lead and 205 patients implanted with 5076 lead between March 2009 and September 2014. Cardiac perforation within 30 days of pacemaker implantation occurred in 4 patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P = 0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in 5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic regression analysis, age was significantly associated with cardiac perforation. Congestive heart failure and implantation of right atrial (RA) lead at RA free wall or septum were significant factors for the incidence of lead dislodgement and lead revision. The incidence of cardiac perforation and lead dislodgement were not statistically different between the patients with 5086 lead and the patients with 5076 lead. However, careful attention for cardiac perforation may be needed when using the 5086 MRI lead, especially in elderly patients. PMID:27510382

  1. Facilitation of calcium-dependent potassium current.

    PubMed

    Thompson, S H

    1994-12-01

    The activation of Ca-dependent K+ current, Ic, was studied in macropatches on the cell bodies of molluscan neurons. When a depolarizing voltage-clamp pulse was applied repeatedly, Ic facilitated in a manner that resembled the facilitation of synaptic transmitter release. Facilitation was characterized by an increase in Ic amplitude, a progressive increase in instantaneous outward current, and a decrease in utilization time. Experiments were done to investigate the mechanism responsible for Ic facilitation. Facilitation was reduced by microinjection of an exogenous Ca2+ buffer into the cytoplasm, indicating that facilitation is a Ca(2+)-dependent process. It was also reduced at elevated temperatures. Conversely, facilitation was greatly potentiated by blocking the Na/Ca exchange mechanism. It is concluded that the facilitation of Ca-dependent K+ current results from the accumulation of Ca2+ at the inner face of the membrane during the repeated activation of Ca2+ channels by depolarization. The Ca2+ indicator fluo-3 was used in fluorescence imaging experiments to measure changes in [Ca]i near the cell membrane during repeated depolarizing pulses and the interpretation of these results was aided by numerical simulations of Ca2+ accumulation, diffusion, and buffering in the peripheral cytoplasm. These experiments showed that the time course of Ic facilitation matches the time course of Ca2+ accumulation at the membrane. It was found that the strength of Ic facilitation varies among patches on the same neuron, suggesting that the accumulation of Ca2+ is not uniform along the inner surface of the membrane and that gradients in [Ca]i develop and are maintained during trains of depolarizing pulses. Potential mechanisms that may lead to local differences in Ca2+ accumulation and Ic facilitation are discussed.

  2. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  3. Sleep facilitates long-term face adaptation

    PubMed Central

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  4. Challenges of Drug-Facilitated Sexual Assault.

    PubMed

    LeBeau, M A; Montgomery, M A

    2010-01-01

    This article provides the reader with an understanding of the numerous challenges of drug-facilitated sexual assaults (DFSA). The challenges are categorized as follows: the drugs, reporting the crime, evidence collection, and laboratory analysis of specimens. The challenges associated with the drugs used to commit DFSA emphasizes the pharmacological effects of strong central nervous system depressants and how the pharmacokinetics and pharmacodynamics of these drugs create difficulties in an investigation. For example, while sexual assaults are generally considered to be a significantly underreported crime, the drug effects further complicate victims' reporting to law enforcement. Any delay in reporting decreases the ability of a laboratory to detect the presence of drugs or metabolites in useful evidentiary specimens such as blood and urine. Finally, differences in instrumentation and mission from one laboratory to the next will impact the ability to provide consistent identification of DFSA drugs or metabolites in these cases. Although the true prevalence of DFSAs will never be fully known, acknowledgment of the many challenges that come with these cases provides insight as to how to improve chances of successfully investigating DFSA allegations.

  5. Protected areas facilitate species’ range expansions

    PubMed Central

    Thomas, Chris D.; Gillingham, Phillipa K.; Bradbury, Richard B.; Roy, David B.; Anderson, Barbara J.; Baxter, John M.; Bourn, Nigel A. D.; Crick, Humphrey Q. P.; Findon, Richard A.; Fox, Richard; Hodgson, Jenny A.; Holt, Alison R.; Morecroft, Mike D.; O’Hanlon, Nina J.; Oliver, Tom H.; Pearce-Higgins, James W.; Procter, Deborah A.; Thomas, Jeremy A.; Walker, Kevin J.; Walmsley, Clive A.; Wilson, Robert J.; Hill, Jane K.

    2012-01-01

    The benefits of protected areas (PAs) for biodiversity have been questioned in the context of climate change because PAs are static, whereas the distributions of species are dynamic. Current PAs may, however, continue to be important if they provide suitable locations for species to colonize at their leading-edge range boundaries, thereby enabling spread into new regions. Here, we present an empirical assessment of the role of PAs as targets for colonization during recent range expansions. Records from intensive surveys revealed that seven bird and butterfly species have colonized PAs 4.2 (median) times more frequently than expected from the availability of PAs in the landscapes colonized. Records of an additional 256 invertebrate species with less-intensive surveys supported these findings and showed that 98% of species are disproportionately associated with PAs in newly colonized parts of their ranges. Although colonizing species favor PAs in general, species vary greatly in their reliance on PAs, reflecting differences in the dependence of individual species on particular habitats and other conditions that are available only in PAs. These findings highlight the importance of current PAs for facilitating range expansions and show that a small subset of the landscape receives a high proportion of colonizations by range-expanding species. PMID:22893689

  6. The Role of Touch in Facilitated Communication.

    ERIC Educational Resources Information Center

    Kezuka, Emiko

    1997-01-01

    A study investigated the role of touch in the use of facilitated communication with Japanese individuals with autism. Five experiments were conducted involving a "telepathy game" using a rod with an attached strain gauge. Results found the facilitator's contact controlled the motor responses of the subjects. (Author/CR)

  7. Caring and Sharing: Becoming a Peer Facilitator.

    ERIC Educational Resources Information Center

    Myrick, Robert D.; Erney, Tom

    This book contains information and skill-building activities designed to train adolescents as peer facilitators. The first chapter describes peer facilitation and provides an overview of the book. The second chapter discusses principles, concepts, and ideas to help better understand how people learn, make decisions, change, and develop their own…

  8. Facilitated Communication: The Clinical and Social Phenomenon.

    ERIC Educational Resources Information Center

    Shane, Howard C., Ed.

    This text explains the phenomenon of facilitated communication (FC) from an empirical, data-based, and/or clinical perspective. It is not a how-to-facilitate text, but one that explores the clinical and sociological reality of FC. A common theme running through each of the papers in the book is the question of FC's legitimacy. The papers reveal…

  9. Interaction Patterns and Facilitation of Peer Learning.

    ERIC Educational Resources Information Center

    Shaw, Marvin E.; And Others

    1979-01-01

    Data show that giving information to members of a group is more important in determining the perception by others that the person is facilitating group performance. Asking for information and opinions is more important in actual facilitation of group learning. Social-emotional support becomes important after initial phases of group interaction.…

  10. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  11. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  12. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  13. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  14. A Dialogic Approach to Online Facilitation

    ERIC Educational Resources Information Center

    Swann, Jennie

    2010-01-01

    Social construction of understanding has long been a significant underlying principle of learning and teaching, and while there are many models for the design of online activities to promote this, there are considerably fewer models for the facilitation of such dialogue. This paper examines some of these facilitation models from the point of view…

  15. Getting the Words Out: Facilitated Communication Training.

    ERIC Educational Resources Information Center

    Crossley, Rosemary; Remington-Gurney, Jane

    1992-01-01

    This paper discusses the use of facilitated communication training with individuals labeled as intellectually impaired, including individuals diagnosed as autistic, at the DEAL Communication Centre in Victoria, Australia. The paper describes the clients, hand use problems addressed by facilitation, literacy, structuring success, fading support,…

  16. "Stepping Up": A Focus on Facilitator Development

    ERIC Educational Resources Information Center

    Kostouros, Patricia; Warthe, D. Gaye; Carter-Snell, Catherine; Burnett, Che

    2016-01-01

    This article examines the impact on peer facilitators in "Stepping Up," a dating violence prevention program at a Canadian university. A focus group held eight months following the delivery of the program determined the personal impact of involvement in the program. Results indicate that peer facilitators experienced personal growth as…

  17. 49 CFR 38.2 - Equivalent facilitation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Equivalent facilitation. 38.2 Section 38.2 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES General § 38.2 Equivalent facilitation. Departures from...

  18. Facilitator Talk in EAP Reading Classes

    ERIC Educational Resources Information Center

    Wilson, Kate

    2008-01-01

    Current sociocultural perspectives on language learning call on teachers to reinvent themselves in ways which facilitate student learning rather than transmit knowledge. For teachers, this means adopting new roles, and acquiring a new repertoire of teacher talk. This paper aims to further the work on facilitator talk begun by Clifton (2006) and…

  19. Toward Facilitative Mentoring and Catalytic Interventions

    ERIC Educational Resources Information Center

    Smith, Melissa K.; Lewis, Marilyn

    2015-01-01

    In TESOL teacher mentoring, giving advice can be conceptualized as a continuum, ranging from directive to facilitative feedback. The goal, over time, is to lead toward the facilitative end of the continuum and specifically to catalytic interventions that encourage self-reflection and autonomous learning. This study begins by examining research on…

  20. Facilitative Leadership: How Principals Lead without Dominating.

    ERIC Educational Resources Information Center

    Conley, David T.; Goldman, Paul

    1994-01-01

    "Facilitative leadership" may be defined as the ability of principals to lead without controlling, while making it easier for all members of the school community to achieve agreed-upon goals. The bulk of the Bulletin consists of a discussion of 10 propositions related to facilitative leadership drawn from 3 sources: (1) studies in…

  1. The Limited Facilitative Effect of Typographical Signals.

    ERIC Educational Resources Information Center

    Golding, Jonathan M.; Fowler, Susan B.

    1992-01-01

    Two experiments with 188 college students investigated the facilitative effect of typographical signals such as underlining, headings, or other devices to help readers identify specific points. Results do not support a general facilitative effect of typographical signals but suggest that use of signals depends on the reader's strategic processing.…

  2. Active and involuntary tobacco smoking and upper-aerodigestive-tract cancer risks in a multicenter case-control study

    PubMed Central

    Lee, Yuan-Chin Amy; Marron, Manuela; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Pohlabeln, Hermann; Lagiou, Pagona; Trichopoulos, Dimitrios; Agudo, Antonio; Castellsague, Xavier; Bencko, Vladimir; Holcatova, Ivana; Kjaerheim, Kristina; Merletti, Franco; Richiardi, Lorenzo; Macfarlane, Gary J.; Macfarlane, Tatiana V.; Talamini, Renato; Barzan, Luigi; Canova, Cristina; Simonato, Lorenzo; Conway, David I.; McKinney, Patricia A.; Lowry, Raymond J.; Sneddon, Linda; Znaor, Ariana; Healy, Claire M.; McCartan, Bernard E.; Brennan, Paul; Hashibe, Mia

    2012-01-01

    Introduction Several important issues for the established association between tobacco smoking and upper-aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers, and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large scale case-control study in Europe. Methods Analysis was performed on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the Alcohol-Related Cancers and Genetic Susceptibility in Europe (ARCAGE) project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was performed to obtain odds ratios (OR) and 95% confidence intervals (CI). Results Compared to never tobacco smoking, current smoking was associated with UADT cancer risks (OR=6.72, 95% CI 5.45–8.30 for overall; 5.83, 4.50–7.54 for oral cavity and oropharynx; 12.19, 8.29–17.92 for hypopharynx and larynx; 4.17, 2.45–7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking packyears were observed for hypopharyngeal and laryngeal cancers (ptrend = 0.01), but not for oral cavity and oropharyngeal cancers (ptrend = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR=1.60, 95% CI 1.04–2.46). Conclusion Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence. PMID:19959682

  3. Developing a survey of barriers and facilitators to recruitment in randomized controlled trials

    PubMed Central

    2012-01-01

    Background Recruitment to randomized controlled trials is known to be challenging. It is important to understand and identify predictors of good or poor accrual to a clinical trial so that appropriate strategies can be put in place to overcome these problems and facilitate successful trial completion. We have developed a survey tool to establish the recruitment experience of clinical teams regarding facilitators and barriers to recruitment in a clinical trial and describe herein the method of developing the questionnaire. Methods A literature search was conducted to identify studies that have explored facilitators and barriers to recruitment, and a list of potential factors affecting recruitment to a clinical trial was generated. These factors were categorized in terms relating to the (i) trial, (ii) site, (iii) patient, (iv) clinical team, (v) information and consent and (vi) study team. A list was provided for responders to grade these factors as weak, intermediate or strong facilitators or barriers to recruitment. Results A web-based survey questionnaire was developed. This survey was designed to establish the recruitment experience of clinical teams with regard to the perceived facilitators and barriers to recruitment, to identify strategies applied to overcome these problems, and to obtain suggestions for change in the organization of future trials. The survey tool can be used to assess the recruitment experience of clinical teams in a single/multicenter trial in any clinical setting or speciality involving adults or children either in an ongoing trial or at trial completion. The questionnaire is short, easy to administer and to complete, with an estimated completion time of 11 minutes. Conclusions We have presented a robust methodology for developing this survey tool that provides an evidence-based list of potential factors that can affect recruitment to a clinical trial. We recommend that all clinical trialists should consider using this tool with

  4. Solution of multi-center molecular integrals of Slater-type orbitals

    NASA Technical Reports Server (NTRS)

    Tai, H.

    1989-01-01

    The troublesome multi-center molecular integrals of Slater-type orbitals (STO) in molecular physics calculations can be evaluated by using the Fourier transform and proper coupling of the two center exchange integrals. A numerical integration procedure is then readily rendered to the final expression in which the integrand consists of well known special functions of arguments containing the geometrical arrangement of the nuclear centers and the exponents of the atomic orbitals. A practical procedure was devised for the calculation of a general multi-center molecular integrals coupling arbitrary Slater-type orbitals. Symmetry relations and asymptotic conditions are discussed. Explicit expressions of three-center one-electron nuclear-attraction integrals and four-center two-electron repulsion integrals for STO of principal quantum number n=2 are listed. A few numerical results are given for the purpose of comparison.

  5. Facilitated versus Non-Facilitated Online Case Discussions: Comparing Differences in Problem Space Coverage

    ERIC Educational Resources Information Center

    Ertmer, Peggy A.; Koehler, Adrie A.

    2015-01-01

    The facilitator plays a key role in guiding students' efforts during case discussions. However, few studies have compared differences in learning outcomes for students participating in facilitated versus non-facilitated discussions. In this research, we used "problem space coverage" as a learning measure to compare outcomes between…

  6. Analysis of β-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey.

    PubMed

    Logan, Latania K; Hujer, Andrea M; Marshall, Steven H; Domitrovic, T Nicholas; Rudin, Susan D; Zheng, Xiaotian; Qureshi, Nadia K; Hayden, Mary K; Scaggs, Felicia A; Karadkhele, Anand; Bonomo, Robert A

    2016-06-01

    Multidrug-resistant (MDR) Enterobacteriaceae infections are increasing in U.S. children; however, there is a paucity of multicentered analyses of antibiotic resistance genes responsible for MDR phenotypes among pediatric Enterobacteriaceae isolates. In this study, 225 isolates phenotypically identified as extended-spectrum β-lactamase (ESBL) or carbapenemase producers, recovered from children ages 0 to 18 years hospitalized between January 2011 and April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type β-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence typing (MLST) were performed to assess isolate similarity. Plasmid replicon typing was conducted to classify plasmids. The median patient age was 4.2 years, 56% were female, and 44% presented in the outpatient setting. The majority (60.9%) of isolates were Escherichia coli and from urinary sources (69.8%). Of 225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7% contained a bla gene. The most common genotype was the blaCTX-M-1 group (49.8%); 1.8% were carbapenem-resistant Enterobacteriaceae (three blaKPC and one blaIMP). Overall, pAmpC (blaACT/MIR and blaCMY) were present in 14.2%. The predominant E. coli phylogenetic group was the virulent B2 group (67.6%) associated with ST43/ST131 (Pasteur/Achtman MLST scheme) containing the blaCTX-M-1 group (84%), and plasmid replicon types FIA, FII, and FIB. K. pneumoniae harboring blaKPC were non-ST258 with replicon types I1 and A/C. Enterobacter spp. carrying blaACT/MIR contained plasmid replicon FIIA. We found that β-lactam resistance in children is diverse and that certain resistance mechanisms differ from known circulating genotypes in adults in an endemic area. The potential impact of complex molecular types and the silent dissemination of MDR Enterobacteriaceae in a vulnerable population needs to be studied further.

  7. Endoscopic third ventriculostomy in children: prospective, multicenter results from the Hydrocephalus Clinical Research Network.

    PubMed

    Kulkarni, Abhaya V; Riva-Cambrin, Jay; Holubkov, Richard; Browd, Samuel R; Cochrane, D Douglas; Drake, James M; Limbrick, David D; Rozzelle, Curtis J; Simon, Tamara D; Tamber, Mandeep S; Wellons, John C; Whitehead, William E; Kestle, John R W

    2016-10-01

    OBJECTIVE Endoscopic third ventriculostomy (ETV) is now established as a viable treatment option for a subgroup of children with hydrocephalus. Here, the authors report prospective, multicenter results from the Hydrocephalus Clinical Research Network (HCRN) to provide the most accurate determination of morbidity, complication incidence, and efficacy of ETV in children and to determine if intraoperative predictors of ETV success add substantially to preoperative predictors. METHODS All children undergoing a first ETV (without choroid plexus cauterization) at 1 of 7 HCRN centers up to June 2013 were included in the study and followed up for a minimum of 18 months. Data, including detailed intraoperative data, were prospectively collected as part of the HCRN's Core Data Project and included details of patient characteristics, ETV failure (need for repeat hydrocephalus surgery), and, in a subset of patients, postoperative complications up to the time of discharge. RESULTS Three hundred thirty-six eligible children underwent initial ETV, 18.8% of whom had undergone shunt placement prior to the ETV. The median age at ETV was 6.9 years (IQR 1.7-12.6), with 15.2% of the study cohort younger than 12 months of age. The most common etiologies were aqueductal stenosis (24.8%) and midbrain or tectal lesions (21.2%). Visible forniceal injury (16.6%) was more common than previously reported, whereas severe bleeding (1.8%), thalamic contusion (1.8%), venous injury (1.5%), hypothalamic contusion (1.5%), and major arterial injury (0.3%) were rare. The most common postoperative complications were CSF leak (4.4%), hyponatremia (3.9%), and pseudomeningocele (3.9%). New neurological deficit occurred in 1.5% cases, with 0.5% being permanent. One hundred forty-one patients had documented failure of their ETV requiring repeat hydrocephalus surgery during follow-up, 117 of them during the first 6 months postprocedure. Kaplan-Meier rates of 30-day, 90-day, 6-month, 1-year, and 2-year failure

  8. Maternal outcome in pregnant women with lupus nephritis. A prospective multicenter study.

    PubMed

    Moroni, Gabriella; Doria, Andrea; Giglio, Elisa; Imbasciati, Enrico; Tani, Chiara; Zen, Margherita; Strigini, Francesca; Zaina, Barbara; Tincani, Angela; Gatto, Mariele; de Liso, Federica; Grossi, Claudia; Meroni, Pier Luigi; Cabiddu, Gianfranca; Messa, Piergiorgio; Ravani, Pietro; Mosca, Marta

    2016-11-01

    Retrospective studies reported a high incidence of maternal complications in pregnant women with lupus. In this paper we prospectively assessed the rate of risk and the risk factors of maternal outcome in women with stable lupus nephritis who received pre-pregnancy counseling. This prospective multicenter study includes 71 pregnancies in 61 women with lupus nephritis who became pregnant between 2006 and 2013. Complete renal remission was present before pregnancy in 56 cases (78.9%) and mild active nephritis in 15 cases. All women underwent a screening visit before pregnancy and were closely monitored by a multidisciplinary team. Lupus anticoagulant, serum C3 and C4 complement fractions, anti-DNA antibodies, anti-C1q antibodies, anticardiolipin IgG and IgM antibodies, anti-beta2 IgG and IgM antibodies were tested at screening visit, at first, second, third trimester of pregnancy, and one year after delivery. Renal flares of lupus during or after pregnancy, pre-eclampsia, and HELLP syndrome were defined as adverse maternal outcomes. Fourteen flares (19.7%), six cases of pre-eclampsia (8.4%) and two cases of HELLP (2.8%) occurred during the study period. All flares responded to therapy and the manifestations of pre-eclampsia and HELLP were promptly reversible. Low C3, high anti-DNA antibodies and predicted all renal flares. High anti-C1q antibodies and low C4 predicted early flares. The body mass index (BMI) was associated with increased risk of late flares. History of previous renal flares and the presence of clinically active lupus nephritis at conception did not increase the risk of renal flares during pregnancy. History of renal flares before pregnancy, arterial hypertension, and longer disease predicted pre-eclampsia/HELLP. In pregnant women with lupus nephritis adverse maternal outcomes were relatively common but proved to be reversible when promptly diagnosed and treated. Immunological activity, arterial hypertension and BMI may predispose to maternal

  9. Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia

    PubMed Central

    Bohorquez, Mabel; Sahasrabudhe, Ruta; Criollo, Angel; Sanabria-Salas, María Carolina; Vélez, Alejandro; Castro, Jorge Mario; Marquez, Juan Ricardo; Mateus, Gilbert; Bolaños, Fernando; Panqueva, Cesar; Restrepo, Jose Ignacio; Puerta, Juan Dario; Murillo, Raul; Bravo, María Mercedes; Hernández, Gustavo; Rios, Angela; Prieto, Rodrigo; Tomlinson, Ian; Echeverry, Magdalena; Carvajal-Carmona, Luis G.

    2016-01-01

    Abstract Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America. The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations. The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3–T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001). To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations. PMID:27749544

  10. Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia.

    PubMed

    Bohorquez, Mabel; Sahasrabudhe, Ruta; Criollo, Angel; Sanabria-Salas, María Carolina; Vélez, Alejandro; Castro, Jorge Mario; Marquez, Juan Ricardo; Mateus, Gilbert; Bolaños, Fernando; Panqueva, Cesar; Restrepo, Jose Ignacio; Puerta, Juan Dario; Murillo, Raul; Bravo, María Mercedes; Hernández, Gustavo; Rios, Angela; Prieto, Rodrigo; Tomlinson, Ian; Echeverry, Magdalena; Carvajal-Carmona, Luis G

    2016-10-01

    Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3-T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

  11. Comorbidities and Phenotypes of Rhinitis in Korean Children and Adolescents: A Cross-sectional, Multicenter Study

    PubMed Central

    Lee, Kyung Suk; Yum, Hye Yung; Sheen, Youn Ho; Park, Yong Mean; Lee, Yong Ju; Choi, Bong Seok; Jee, Hye Mi; Choi, Sun Hee; Kim, Hyun Hee; Park, Yang; Kim, Hyo-Bin

    2017-01-01

    Purpose Rhinitis is a nasal inflammatory disease in children and adolescents. However, little is known about the phenotypes and characteristics of allergic rhinitis (AR) in Korean children and adolescents. The objective of this study was to analyze the symptoms and comorbidities of rhinitis, to compare AR to non-allergic rhinitis (NAR), and to reveal the phenotypes and features of AR in a Korean pediatric population. Methods Patients under 18 years of age with rhinitis symptoms were recruited from January 2013 to January 2015 by pediatric allergists. We analyzed symptoms, phenotypes, comorbidities, and allergen sensitization in this cross-sectional, multicenter study. Results Medical records were collected from 11 hospitals. The AR group has 641 (68.3%) patients, with 63.2% of boys and 7.5 (±3.4) years of mean age. The NAR group has 136 (14.5%) patients, with 55.1% of boys and 5.5 (±2.9) years of mean age. Moderate-severe persistent AR affected 41.2% of AR patients. Nasal obstruction was more common in NAR patients (P<0.050), whereas AR patients sneezed more (P<0.050) and more commonly had conjunctivitis, asthma, and otitis media (P<0.050). Sinusitis was the most common comorbidity in both groups. Allergen sensitization was caused by house dust mites (HDMs) (90.2%), pollen (38.7%), and animal dander (24.8%) in AR patients. Pollen and animal dander sensitization significantly increased age-dependently (P<0.050), but 91.9% of AR patients were already sensitized to HDMs before 5 years old. Conclusions Our study revealed that AR was more prevalent than NAR and that 41.2% of AR presented with moderate-severe disease in Korean pediatric populations. Sinusitis was the most common comorbidity, and sleep disturbance was associated with the severity of rhinitis. The majority of AR patients were sensitized to HDMs in preschool ages. Further studies, including nationwide and longitudinal data, will help understand the relationship between these diseases. PMID:27826964

  12. Multicenter epidemiological and clinical study on imported Chagas diseases in Alicante, Spain

    PubMed Central

    Ramos, José M; Torrús, Diego; Amador, Concepción; Jover, Francisco; Pérez-Chacón, Fabiola; Ponce, Yamileth; Arjona, Francisco J; Caro, Elena; Martínez-Peinado, Concepción; Gallegos, Ingrid; Cuadrado, José M; Tello, Antonio; Gutiérrez, Felix

    2012-01-01

    Recently, there has been an increase in the number of patients with Chagas disease outside of areas that are generally considered endemic. The aim of this investigation is to describe the clinical profile of a series of patients with Chagas disease in Alicante, Spain, which is a province located on the coast of the Mediterranean Sea. This study was performed at four general hospitals in Alicante between January 2002 and May 2011. A total of 128 patients from seven countries were diagnosed with Trypanosoma cruzi. The main country of origin of these patients was Bolivia (n = 101; 78.9%), and the median of age of these patients was 35 years (range: 0–72 years). Four (3.3%) patients were children under 14 years of age, and 81 (63.3%) were female. Polymerase chain reaction (PCR) was used to analyze 106 patients, 66.0% of whom demonstrated positive PCR results. Visceral involvement was diagnosed in 26.8%: 24.1% demonstrated cardiac involvement, 0.9% demonstrated gastrointestinal involvement, 0.9% demonstrated cardiac and gastrointestinal involvement, and 0.9% demonstrated involvement of the central nervous system. Syncope was found to be associated with cardiomyopathy (28.0% versus 5.2%) (odds ratio: 6.5; 95% confidence interval: 1.5–27.1). Seventy-six patients received treatment with benznidazole, of whom 57 (75.0%) completed the treatment course without significant adverse events and 17.1% discontinued benznidazole due to adverse events. In total, 50% of patients experienced documented adverse reactions. Among patients with positive PCR results before treatment, all demonstrated negative PCR results following treatment. In conclusion, majority of our patients were female Bolivians immigrants, one of four of our patients demonstrated cardiac involvement, and treatment tolerance was poor. It is important to improve the clinical and epidemiological knowledge of Chagas disease in nonendemic with additional multicenter studies in order to determine the magnitude of

  13. Analysis of β-Lactamase Resistance Determinants in Enterobacteriaceae from Chicago Children: a Multicenter Survey

    PubMed Central

    Hujer, Andrea M.; Marshall, Steven H.; Domitrovic, T. Nicholas; Rudin, Susan D.; Zheng, Xiaotian; Qureshi, Nadia K.; Hayden, Mary K.; Scaggs, Felicia A.; Karadkhele, Anand; Bonomo, Robert A.

    2016-01-01

    Multidrug-resistant (MDR) Enterobacteriaceae infections are increasing in U.S. children; however, there is a paucity of multicentered analyses of antibiotic resistance genes responsible for MDR phenotypes among pediatric Enterobacteriaceae isolates. In this study, 225 isolates phenotypically identified as extended-spectrum β-lactamase (ESBL) or carbapenemase producers, recovered from children ages 0 to 18 years hospitalized between January 2011 and April 2015 at three Chicago area hospitals, were analyzed. We used DNA microarray platforms to detect ESBL, plasmid-mediated AmpC (pAmpC), and carbapenemase type β-lactamase (bla) genes. Repetitive-sequence-based PCR and multilocus sequence typing (MLST) were performed to assess isolate similarity. Plasmid replicon typing was conducted to classify plasmids. The median patient age was 4.2 years, 56% were female, and 44% presented in the outpatient setting. The majority (60.9%) of isolates were Escherichia coli and from urinary sources (69.8%). Of 225 isolates exhibiting ESBL- or carbapenemase-producing phenotypes, 90.7% contained a bla gene. The most common genotype was the blaCTX-M-1 group (49.8%); 1.8% were carbapenem-resistant Enterobacteriaceae (three blaKPC and one blaIMP). Overall, pAmpC (blaACT/MIR and blaCMY) were present in 14.2%. The predominant E. coli phylogenetic group was the virulent B2 group (67.6%) associated with ST43/ST131 (Pasteur/Achtman MLST scheme) containing the blaCTX-M-1 group (84%), and plasmid replicon types FIA, FII, and FIB. K. pneumoniae harboring blaKPC were non-ST258 with replicon types I1 and A/C. Enterobacter spp. carrying blaACT/MIR contained plasmid replicon FIIA. We found that β-lactam resistance in children is diverse and that certain resistance mechanisms differ from known circulating genotypes in adults in an endemic area. The potential impact of complex molecular types and the silent dissemination of MDR Enterobacteriaceae in a vulnerable population needs to be studied further

  14. Place of upper endoscopy before and after bariatric surgery: A multicenter experience with 3219 patients

    PubMed Central

    Abd Ellatif, Mohamed E; Alfalah, Haitham; Asker, Walid A; El Nakeeb, Ayman E; Magdy, Alaa; Thabet, Waleed; Ghaith, Mohamed A; Abdallah, Emad; Shahin, Rania; Shoma, Asharf; Dawoud, Ibraheim E; Abbas, Ashraf; Salama, Asaad F; Ali Gamal, Maged

    2016-01-01

    AIM: To study the preoperative and postoperative role of upper esophagogastroduodenoscopy (EGD) in morbidly obese patients. METHODS: This is a multicenter retrospective study by reviewing the database of patients who underwent bariatric surgery (laparoscopic sleeve gastrectomy, laparoscopic Roux en Y gastric bypass, or laparoscopic minigastric bypass) in the period between 2001 June and 2015 August (Jahra Hospital-Kuwait, Hafr Elbatin Hospital and King Saud Medical City-KSA, and Mansoura University Hospital - Egypt). Patients with age 18-65 years, body mass index (BMI) > 40, or > 35 with comorbidities after failure of many dietetic regimen and acceptable levels of surgical risk were included in the study after having an informed signed consent. We retrospectively reviewed the medical charts of all morbidly obese patients. The patients’ preoperative data included clinical history including upper digestive symptoms and preoperative full workup including EGD. Only patients whose charts revealed weather they were symptomatic or not were studied. We categorized patients accordingly into two groups; with (group A) or without (group B) upper digestive symptoms. The endoscopic findings were categorized into 4 groups based on predetermined criteria. The medical record of patients who developed stricture, leak or bleeding after bariatric surgery was reviewed. Logestic regression analysis was used to identify preoperative predictors that might be associated with abnormal endoscopic findings. RESULTS: Three thousand, two hundred and nineteen patients in the study period underwent bariatric surgery (75% LSG, 10% LRYDB, and 15% MGB). Mean BMI was 43 ± 13, mean age 37 ± 9 years, 79% were female. Twenty eight percent had presented with upper digestive symptoms (group A). EGD was considered normal in 2414 (75%) patients (9% group A vs 66% group B, P = 0.001). The abnormal endoscopic findings were found high in those patients with upper digestive symptoms. Abnormal findings (one

  15. Serious gaming and voluntary laparoscopic skills training: a multicenter study.

    PubMed

    Verdaasdonk, E G G; Dankelman, J; Schijven, M P; Lange, J F; Wentink, M; Stassen, L P S

    2009-01-01

    This study assesses the issue of voluntary training of a standardized online competition (serious gaming) between surgical residents. Surgical residents were invited to join a competition on a virtual reality (VR) simulator for laparoscopic motor skills. A final score was calculated based on the task performance of three exercises and was presented to all the participants through an online database on the Internet. The resident with the best score would win a lap-top computer. During three months, 31 individuals from seven hospitals participated (22 surgical residents, 3 surgeons and six interns). A total of 777 scores were logged in the database. In order to out-perform others some participants scheduled themselves voluntarily for additional training. More attempts correlated with higher scores. The serious gaming concept may enhance voluntary skills training. Online data capturing could facilitate monitoring of skills progression in surgical trainees and enhance (VR) simulator validation.

  16. Turner Syndrome and Associated Problems in Turkish Children: A Multicenter Study

    PubMed Central

    Yeşilkaya, Ediz; Bereket, Abdullah; Darendeliler, Feyza; Baş, Firdevs; Poyrazoğlu, Şükran; Küçükemre Aydın, Banu; Darcan, Şükran; Dündar, Bumin; Büyükinan, Muammer; Kara, Cengiz; Sarı, Erkan; Adal, Erdal; Akıncı, Ayşehan; Atabek, Mehmet Emre; Demirel, Fatma; Çelik, Nurullah; Özkan, Behzat; Özhan, Bayram; Orbak, Zerrin; Ersoy, Betül; Doğan, Murat; Ataş, Ali; Turan, Serap; Gökşen, Damla; Tarım, Ömer; Yüksel, Bilgin; Ercan, Oya; Hatun, Şükrü; Şimşek, Enver; Ökten, Ayşenur; Abacı, Ayhan; Döneray, Hakan; Özbek, Mehmet Nuri; Keskin, Mehmet; Önal, Hasan; Akyürek, Nesibe; Bulan, Kezban; Tepe, Derya; Emeksiz, Hamdi Cihan; Demir, Korcan; Kızılay, Deniz; Topaloğlu, Ali Kemal; Eren, Erdal; Özen, Samim; Abalı, Saygın; Akın, Leyla; Selver Eklioğlu, Beray; Kaba, Sultan; Anık, Ahmet; Baş, Serpil; Ünüvar, Tolga; Sağlam, Halil; Bolu, Semih; Özgen, Tolga; Doğan, Durmuş; Çakır, Esra Deniz; Şen, Yaşar; Andıran, Nesibe; Çizmecioğlu, Filiz; Evliyaoğlu, Olcay; Karagüzel, Gülay; Pirgon, Özgür; Çatlı, Gönül; Can, Hatice Dilek; Gürbüz, Fatih; Binay, Çiğdem; Baş, Veysel Nijat; Fidancı, Kürşat; Polat, Adem; Gül, Davut; Açıkel, Cengizhan; Demirbilek, Hüseyin; Cinaz, Peyami; Bondy, Carolyn

    2015-01-01

    Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. PMID:25800473

  17. Coagulation defects associated with massive blood transfusion: A large multicenter study.

    PubMed

    Yang, Jiang-Cun; Sun, Yang; Xu, Cui-Xiang; Dang, Qian-Li; Li, Ling; Xu, Yong-Gang; Song, Yao-Jun; Yan, Hong

    2015-09-01

    The variations in the coagulation indices of patients receiving massive blood transfusion were investigated across 20 large‑scale general hospitals in China. The data of 1,601 surgical inpatients receiving massive transfusion were retrospectively collected and the trends in the platelet counts and coagulation indices prior to and at 16 different time points during packed red blood cell (pRBC; after 2‑40 units of pRBC) transfusion were evaluated by linear regression analysis. Temporal variations in the means of prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT) and fibrinogen (FIB) concentration were also assessed and the theoretical estimates and actual measurements of the platelet count were compared. The results demonstrated that the platelet count decreased linearly with an increase in the number of pRBC units transfused (Y=150.460‑3.041X; R2 linear=0.775). Following transfusion of 18 units of pRBC (0.3 units of pRBC transfused per kilogram of body weight), the average platelet count decreased to 71x10(9)/l (<75x10(9)/l). Furthermore, variations in the means of PT, INR, APTT and FIB did not demonstrate any pronounced trends and actual platelet counts were markedly higher than the theoretical estimates. In conclusion, no variations in the means of traditional coagulation indices were identified, however, the platelet count demonstrated a significant linear decrease with an increase in the number of pRBC units transfused. Furthermore, actual platelet counts were higher than theoretical estimates, indicating the requirement for close monitoring of actual platelet counts during massive pRBC transfusion.

  18. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

    PubMed Central

    Borba, Helena HL; Wiens, Astrid; Steimbach, Laiza M; Tonin, Fernanda S; Pedroso, Maria LA; Ivantes, Cláudia AP; Fernandez-Llimos, Fernando; Pontarolo, Roberto

    2017-01-01

    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 had an influence on the RVR rate (odds ratio [OR] =0.011; 95% confidence interval [CI]: 0.001–0.119; P<0.001/OR =13.004; 95% CI: 1.522–111.115; P=0.019, respectively). Conclusion In this longitudinal multicenter cohort study conducted from the Brazilian perspective, differences were found in the RVR rates, favoring telaprevir over boceprevir for genotype 1 HCV-infected patients. In addition, the baseline viral load was associated with RVR achievement in both evaluated groups. As RVR is also reported in the literature as a predictor

  19. Multicenter airborne coherent atmospheric wind sensor (MACAWS) instrument: recent upgrades and results

    NASA Astrophysics Data System (ADS)

    Howell, James N.; Rothermel, Jeffrey; Tratt, David M.; Cutten, Dean; Darby, Lisa S.; Hardesty, R. Michael

    1999-10-01

    The Multicenter Airborne Coherent Atmospheric Wind Sensor instrument is an airborne coherent Doppler laser radar (Lidar) capable of measuring atmospheric wind fields and aerosol structure. Since the first demonstration flights onboard the NASA DC-8 research aircraft in September 1995, two additional science flights have been completed. Several system upgrades have also bee implemented. In this paper we discuss the system upgrades and present several case studies which demonstrate the various capabilities of the system.

  20. Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1: A Multicenter Project With 3 Clinical Trials

    DTIC Science & Technology

    2006-06-01

    Tumors in Neurofibromatosis Type 1: A Multicenter Project with 3 Clinical Trials PRINCIPAL INVESTIGATOR: David Viskochil, M.D., Ph.D...Trials 5b. GRANT NUMBER W81XWH-04-1-0502 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) David Viskochil, M.D., Ph.D. 5d. PROJECT...submission of a clinical trial for neoadjuvant chemotherapy in MPNST (DAMD-NF043129; PI- David Viskochil). This proposal was not funded, however it was

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

    SciTech Connect

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

    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.

  2. OnWARD: ontology-driven web-based framework for multi-center clinical studies.

    PubMed

    Tran, Van-Anh; Johnson, Nathan; Redline, Susan; Zhang, Guo-Qiang

    2011-12-01

    With a large percentage of clinical trials still using paper forms as the primary data collection tool, there is much potential for increasing efficiency through web-based data collection systems, especially for large-scale multi-center trials. This paper presents OnWARD, an ontology-driven, secure, rapidly-deployed, web-based framework supporting data capture for large-scale multi-center clinical research. Our approach is developed using the agile methodology to provide a flexible, user-centered dynamic form generator, which can be quickly deployed and customized for any clinical study without the need of deep technical expertise. Because of the flexible framework, the data management system can be extended to accommodate a large variety of data types, including genetic, genomic and proteomic data. In this paper, we demonstrate the initial deployment of OnWARD for a Phase II multi-center clinical trial after a development period of merely three months. The study utilizes 23 clinical report forms containing more than 1500 data points. Preliminary evaluation results show that OnWARD exceeded expectations of the clinical investigators in efficiency, flexibility and ease in setting up.

  3. LORIS: a web-based data management system for multi-center studies

    PubMed Central

    Das, Samir; Zijdenbos, Alex P.; Harlap, Jonathan; Vins, Dario; Evans, Alan C.

    2012-01-01

    Longitudinal Online Research and Imaging System (LORIS) is a modular and extensible web-based data management system that integrates all aspects of a multi-center study: from heterogeneous data acquisition (imaging, clinical, behavior, and genetics) to storage, processing, and ultimately dissemination. It provides a secure, user-friendly, and streamlined platform to automate the flow of clinical trials and complex multi-center studies. A subject-centric internal organization allows researchers to capture and subsequently extract all information, longitudinal or cross-sectional, from any subset of the study cohort. Extensive error-checking and quality control procedures, security, data management, data querying, and administrative functions provide LORIS with a triple capability (1) continuous project coordination and monitoring of data acquisition (2) data storage/cleaning/querying, (3) interface with arbitrary external data processing “pipelines.” LORIS is a complete solution that has been thoroughly tested through a full 10 year life cycle of a multi-center longitudinal project1 and is now supporting numerous international neurodevelopment and neurodegeneration research projects. PMID:22319489

  4. Multicenter surveillance of species distribution and antifungal susceptibilities of Candida bloodstream isolates in South Korea.

    PubMed

    Jung, Sook-In; Shin, Jong Hee; Song, Jae-Hoon; Peck, Kyong Ran; Lee, Kyungwon; Kim, Mi-Na; Chang, Hyun Ha; Moon, Chi Sook

    2010-06-01

    Multicenter data on in vitro susceptibility of Candida bloodstream isolates to echinocandin antifungal agents is still lacking in South Korea. We performed a prospective multicenter study to determine the species distribution of Candida bloodstream isolates and their susceptibility to five antifungal agents, including caspofungin and micafungin. A total of 639 isolates were collected from 20 tertiary hospitals between September 2006 and August 2007. Antifungal susceptibilities were determined through the use of the CLSI broth microdilution method M27-A3. The overall species distribution was as follows; Candida albicans (38%), Candida parapsilosis (26%), Candia tropicalis (20%), Candida glabrata (11%), and miscellaneous Candida species (5%). Although C. parapsilosis and miscellaneous Candida species were less susceptible to both echinocandins, all 639 isolates were susceptible to both caspofungin and micafungin (MIC, multicenter candidemia study conducted in South Korea and shows that non-C. albicans Candida species, including C. parapsilosis, constitutes over 60% of all Candida species isolates recovered from the bloodstream. In addition, the rates of resistance to all five antifungals, including two echinocandins, are still low among bloodstream isolates in South Korea.

  5. Long-Term Cigarette Smoking Trajectories Among HIV-Seropositive and Seronegative MSM in the Multicenter AIDS Cohort Study.

    PubMed

    Akhtar-Khaleel, Wajiha Z; Cook, Robert L; Shoptaw, Steve; Surkan, Pamela J; Teplin, Linda A; Stall, Ronald; Beyth, Rebecca J; Manini, Todd M; Plankey, Michael

    2016-08-01

    To examine the association between demographic characteristics and long-term smoking trajectory group membership among HIV-seropositive and HIV-seronegative men who have sex with men (MSM). A cohort of 6552 MSM from the Multicenter AIDS Cohort Study were asked detailed information about their smoking history since their last follow-up. Group-based trajectory modeling was used to examine smoking behavior and identify trajectory group membership. Because participants enrolled after 2001 were more likely to be younger, HIV-seronegative, non-Hispanic black, and have a high school diploma or less, we also assessed time of enrollment in our analysis. Participants were grouped into 4 distinct smoking trajectory groups: persistent nonsmoker (n = 3737 [55.9 %]), persistent light smoker (n = 663 [11.0 %]), heavy smoker to nonsmoker (n = 531 [10.0 %]), and persistent heavy smoker (n = 1604 [23.1 %]). Compared with persistent nonsmokers, persistent heavy smokers were associated with being enrolled in 2001 and later (adjusted odds ratio [aOR] 2.35; 95 % CI 2.12-2.58), having a high school diploma or less (aOR 3.22; 95 % CI 3.05-3.39), and being HIV-seropositive (aOR 1.17; 95 % CI 1.01-1.34). These associations were statistically significant across all trajectory groups for time of enrollment and education but not for HIV serostatus. The overall decrease of smoking as shown by our trajectory groups is consistent with the national trend. Characteristics associated with smoking group trajectory membership should be considered in the development of targeted smoking cessation interventions among MSM and people living with HIV.

  6. Long-Term Cigarette Smoking Trajectories Among HIV-Seropositive and Seronegative MSM in the Multicenter AIDS Cohort Study

    PubMed Central

    Akhtar-Khaleel, Wajiha Z; Cook, Robert L.; Shoptaw, Steve; Surkan, Pamela J.; Teplin, Linda A; Stall, Ronald; Beyth, Rebecca J.; Manini, Todd; Plankey, Michael

    2016-01-01

    Objective To examine the association between demographic characteristics and long-term smoking trajectory group membership among HIV-seropositive and HIV-seronegative men who have sex with men (MSM). Methods A cohort of 6,552 MSM from the Multicenter AIDS Cohort Study (MACS) were asked detailed information about their smoking history since their last follow-up. Group-based trajectory modeling was used to examine smoking behavior and identify trajectory group membership. Because participants enrolled after 2001 were more likely to be younger, HIV-seronegative, non-Hispanic black, and have a high school diploma or less, we also assessed time of enrollment in our analysis. Results Participants were grouped into 4 distinct smoking trajectory groups: persistent nonsmoker (n=3,737 [55.9%]), persistent light smoker (n=663 [11.0%]), heavy smoker to nonsmoker (n=531 [10.0%]), and persistent heavy smoker (n=1,604 [23.1%]). Compared with persistent nonsmokers, persistent heavy smokers were associated with being enrolled in 2001 and later (adjusted odds ratio [aOR], 2.35; 95% CI, 2.12-2.58), having a high school diploma or less (aOR, 3.22; 95% CI, 3.05-3.39), and being HIV-seropositive (aOR, 1.17; 95% CI, 1.01-1.34). These associations were statistically significant across all trajectory groups for time of enrollment and education but not for HIV serostatus. Conclusions The overall decrease of smoking as shown by our trajectory groups is consistent with the national trend. Characteristics associated with smoking group trajectory membership should be considered in the development of targeted smoking cessation interventions among MSM and people living with HIV. PMID:26922718

  7. Cardiovascular events in Japan. Lessons from the J-ACCESS multicenter prognostic study using myocardial perfusion imaging.

    PubMed

    Nakajima, Kenichi; Nishimura, Tsunehiko

    2012-01-01

    The multicenter Japanese-Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS), which involved 117 institutions and 4,629 patients, was the first attempt to quantify cardiac events and survival using stress-rest-gated single-photon emission computed tomography myocardial perfusion images (MPI) and QGS software in Japan. A 3-year follow-up study showed a relatively lower incidence of hard events than in the USA and some European countries, but a similar role of perfusion and left ventricular (LV) function. A low event risk with normal MPI and a higher incidence of major cardiac events in patients with large perfusion defects and LV dysfunction were defined. MPI was useful even among patients with proven coronary artery stenosis. The association between diabetes and chronic kidney disease (CKD) was an important predictor of cardiac events and the risk was evaluated using new software and risk charts. Additional studies were extended to include asymptomatic diabetes (J-ACCESS 2) and CKD (J-ACCESS 3). Because risk estimation is linked to the national healthcare system and clinical practice, optimal risk stratification and guidance for therapeutic strategies are recommended.

  8. A new design of a polysomnography-based multi-center treatment study for the restless legs syndrome.

    PubMed

    Penzel, T; Brandenburg, U; Peter, J H; Otto, R; Hundemer, H P; Lledo, A; Wetter, T C; Trenkwalder, C

    2002-04-01

    Periodic limb movements (PLM) cause sleep disorders and daytime symptoms and are frequently associated with restless legs syndrome (RLS). Treatment of RLS with increased PLM during sleep (PLMS) has been evaluated in studies limited in size, methodology and study length. This long-term, placebo-controlled, multi-center, study with polysomnography (PSG) recordings has been designed in order to assess efficacy and safety parameters of pergolide treatment in RLS. This novel approach for a study was created to assure consistently high quality of sleep recording and analysis. Using defined criteria, 21 sleep centers were approved for the study after a pilot phase. Seventeen centers with 16 different PSG systems randomized 100 patients. Digital sleep recordings from 4 visits (baseline, 6 weeks, 6 months, 1 year) were submitted to one central evaluation center following previously defined standardized operating procedures. Visual scoring of all recordings was performed by one independent scorer. Reliability of scoring was evaluated for 20 randomly selected baseline recordings. The mean epoch by epoch agreement for sleep stages was 88% (range 81-96%), mean arousal re-scoring differed by 0.5 (range: -16 to 20), and mean PLM index re-scoring differed by 0.1 (range: -1.5 to 2.1). Using one scorer with a demonstrated high reliability in PSG scoring for all sleep recordings was very effective in terms of study cost, study duration, and data quality.

  9. Evaluation of 5 versus 10 granulocyteaphaeresis sessions in steroid-dependent ulcerative colitis: A pilot, prospective, multicenter, randomized study

    PubMed Central

    Ricart, Elena; Esteve, Maria; Andreu, Montserrat; Casellas, Francesc; Monfort, David; Sans, Miquel; Oudovenko, Natalia; Lafuente, Raúl; Panés, Julián

    2007-01-01

    AIM: To evaluate the efficacy of 5 compared to 10 granulocyteaphaeresis sessions in patients with active steroid-dependent ulcerative colitis. METHODS: In this pilot, prospective, multicenter randomized trial, 20 patients with moderately active steroid-dependent ulcerative colitis were randomized to 5 or 10 granulocyteaphaeresis sessions. The primary objective was clinical remission at wk 17. Secondary measures included endoscopic remission and steroid consumption. RESULTS: Nine patients were randomized to 5 granulocyteaphaeresis sessions (group 1) and 11 patients to 10 granulocyteaphaeresis sessions (group 2). At wk 17, 37.5% of patients in group 1 and 45.45% of patients in group 2 were in clinical remission. Clinical remission was accompanied by endoscopic remission in all cases. Eighty-six percent of patients achieving remission were steroid-free at wk 17. Daily steroid requirements were significantly lower in group 2. Eighty-nine per cent of patients remained in remission during a one year follow-up. One serious adverse event, not related to the study therapy, was reported. CONCLUSION: Granulocyteaphaeresis is safe and effective for the treatment of steroid-dependent ulcerative colitis. In this population, increasing the number of aphaeresis sessions is not associated with higher remission rates, but affords a significant steroid-sparing effect. PMID:17465500

  10. Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study.

    PubMed

    Hamaguchi, Yasuhito; Sumida, Takayuki; Kawaguchi, Yasushi; Ihn, Hironobu; Tanaka, Sumiaki; Asano, Yoshihide; Motegi, Sei-Ichiro; Kuwana, Masataka; Endo, Hirahito; Takehara, Kazuhiko

    2017-01-01

    A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52-week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan.

  11. Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study.

    PubMed

    Plasseraud, Kristen Meldi; Cook, Robert W; Tsai, Tony; Shildkrot, Yevgeniy; Middlebrook, Brooke; Maetzold, Derek; Wilkinson, Jeff; Stone, John; Johnson, Clare; Oelschlager, Kristen; Aaberg, Thomas M

    2016-01-01

    Uveal melanoma management is challenging due to its metastatic propensity. DecisionDx-UM is a prospectively validated molecular test that interrogates primary tumor biology to provide objective information about metastatic potential that can be used in determining appropriate patient care. To evaluate the continued clinical validity and utility of DecisionDx-UM, beginning March 2010, 70 patients were enrolled in a prospective, multicenter, IRB-approved study to document patient management differences and clinical outcomes associated with low-risk Class 1 and high-risk Class 2 results indicated by DecisionDx-UM testing. Thirty-seven patients in the prospective study were Class 1 and 33 were Class 2. Class 1 patients had 100% 3-year metastasis-free survival compared to 63% for Class 2 (log rank test p = 0.003) with 27.3 median follow-up months in this interim analysis. Class 2 patients received significantly higher-intensity monitoring and more oncology/clinical trial referrals compared to Class 1 patients (Fisher's exact test p = 2.1 × 10(-13) and p = 0.04, resp.). The results of this study provide additional, prospective evidence in an independent cohort of patients that Class 1 and Class 2 patients are managed according to the differential metastatic risk indicated by DecisionDx-UM. The trial is registered with Clinical Application of DecisionDx-UM Gene Expression Assay Results (NCT02376920).

  12. Treosulfan-Based Conditioning and Hematopoietic Cell Transplantation for Nonmalignant Diseases: A Prospective Multi-Center Trial

    PubMed Central

    Burroughs, Lauri M.; Nemecek, Eneida R.; Torgerson, Troy R.; Storer, Barry E.; Talano, Julie-An; Domm, Jennifer; Giller, Roger H.; Shimamura, Akiko; Delaney, Colleen; Skoda-Smith, Suzanne; Thakar, Monica S.; Baker, K. Scott; Rawlings, David J.; Englund, Janet A.; Flowers, Mary E. D.; Deeg, H. Joachim; Storb, Rainer; Woolfrey, Ann E.

    2015-01-01

    Hematopoietic cell transplantation (HCT) is effective in the treatment of patients with nonmalignant diseases and for many is the only known cure. Conventional myeloablative regimens have been associated with unacceptably high early transplant-related mortality (TRM) particularly in patients with co-morbid conditions. This prospective multicenter trial was designed to determine the safety and engraftment efficacy of treosulfan-based conditioning in patients with nonmalignant diseases. Thirty-one patients received HLA-matched related (n=4) or unrelated (n=27) grafts following conditioning with treosulfan (total dose: 42 g/m2), fludarabine (total dose: 150 mg/m2), ± thymoglobulin (6 mg/kg; n=22). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate. All patients engrafted. Day-100 TRM was 0%. With a median follow-up of 2 years, the 2-year survival was 90%. Three patients died of GVHD, recurrent hemophagocytic lymphohistiocytosis, and a surgical complication, respectively. The cumulative incidences of grades II–IV and III–IV acute GVHD at day 100 and chronic GVHD at 2 years were 62%, 10% and 21%, respectively. Patients who received thymoglobulin had a significantly lower incidence of grade III-IV acute GVHD (0% versus 33%; P = 0.005). These results indicate that the combination of treosulfan, fludarabine, and thymoglobulin is effective at establishing donor engraftment with low toxicity and improved survival in patients with nonmalignant diseases, and support the need for future disease-specific clinical trials. PMID:25196857

  13. Facilitating Analysis of Multiple Partial Data Streams

    NASA Technical Reports Server (NTRS)

    Maimone, Mark W.; Liebersbach, Robert R.

    2008-01-01

    Robotic Operations Automation: Mechanisms, Imaging, Navigation report Generation (ROAMING) is a set of computer programs that facilitates and accelerates both tactical and strategic analysis of time-sampled data especially the disparate and often incomplete streams of Mars Explorer Rover (MER) telemetry data described in the immediately preceding article. As used here, tactical refers to the activities over a relatively short time (one Martian day in the original MER application) and strategic refers to a longer time (the entire multi-year MER missions in the original application). Prior to installation, ROAMING must be configured with the types of data of interest, and parsers must be modified to understand the format of the input data (many example parsers are provided, including for general CSV files). Thereafter, new data from multiple disparate sources are automatically resampled into a single common annotated spreadsheet stored in a readable space-separated format, and these data can be processed or plotted at any time scale. Such processing or plotting makes it possible to study not only the details of a particular activity spanning only a few seconds, but also longer-term trends. ROAMING makes it possible to generate mission-wide plots of multiple engineering quantities [e.g., vehicle tilt as in Figure 1(a), motor current, numbers of images] that, heretofore could be found only in thousands of separate files. ROAMING also supports automatic annotation of both images and graphs. In the MER application, labels given to terrain features by rover scientists and engineers are automatically plotted in all received images based on their associated camera models (see Figure 2), times measured in seconds are mapped to Mars local time, and command names or arbitrary time-labeled events can be used to label engineering plots, as in Figure 1(b).

  14. Does polyploidy facilitate long-distance dispersal?

    PubMed Central

    Linder, H. Peter; Barker, Nigel P.

    2014-01-01

    Background and Aims The ability of plant lineages to reach all continents contributes substantially to their evolutionary success. This is exemplified by the Poaceae, one of the most successful angiosperm families, in which most higher taxa (tribes, subfamilies) have global distributions. Due to the old age of the ocean basins relative to the major angiosperm radiations, this is only possible by means of long-distance dispersal (LDD), yet the attributes of lineages with successful LDD remain obscure. Polyploid species are over-represented in invasive floras and in the previously glaciated Arctic regions, and often have wider ecological tolerances than diploids; thus polyploidy is a candidate attribute of successful LDD. Methods The link between polyploidy and LDD was explored in the globally distributed grass subfamily Danthonioideae. An almost completely sampled and well-resolved species-level phylogeny of the danthonioids was used, and the available cytological information was assembled. The cytological evolution in the clade was inferred using maximum likelihood (ML) as implemented in ChromEvol. The biogeographical evolution in the clade was reconstructed using ML and Bayesian approaches. Key Results Numerous increases in ploidy level are demonstrated. A Late Miocene–Pliocene cycle of polyploidy is associated with LDD, and in two cases (the Australian Rytidosperma and the American Danthonia) led to secondary polyploidy. While it is demonstrated that successful LDD is more likely in polyploid than in diploid lineages, a link between polyploidization events and LDD is not demonstrated. Conclusions The results suggest that polyploids are more successful at LDD than diploids, and that the frequent polyploidy in the grasses might have facilitated the extensive dispersal among continents in the family, thus contributing to their evolutionary success. PMID:24694830

  15. 31 CFR 537.205 - Prohibited facilitation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the United States. (b) With respect to new investment in Burma, the prohibition against facilitation... may be waived by the President upon the making of certain determinations and notification to...

  16. Suicide: Issues of Prevention, Intervention, and Facilitation.

    ERIC Educational Resources Information Center

    Nelson, Franklyn L.

    1984-01-01

    Discusses the concept of suicide intervention which allows for the possibility of death facilitation as well as prevention. A proposed suicide intervention model is contrasted with the goals and methods of existing suicide prevention and crisis counseling services. (JAC)

  17. Dream Deprivation and Facilitation with Hypnosis

    ERIC Educational Resources Information Center

    Albert, Ira B.; Boone, Donald

    1975-01-01

    The present study attempted to deprive human subjects of dreaming through the administration of a posthypnotic suggestion and to increase or facilitate dreaming through a second suggestion that was used with another group of subjects. (Author/RK)

  18. Facilitating LOS Debriefings: A Training Manual

    NASA Technical Reports Server (NTRS)

    McDonnell, Lori K.; Jobe, Kimberly K.; Dismukes, R. Key

    1997-01-01

    This manual is a practical guide to help airline instructors effectively facilitate debriefings of Line Oriented Simulations (LOS). It is based on a recently completed study of Line Oriented Flight Training (LOFT) debriefings at several U.S. airlines. This manual presents specific facilitation tools instructors can use to achieve debriefing objectives. The approach of the manual is to be flexible so it can be tailored to the individual needs of each airline. Part One clarifies the purpose and objectives of facilitation in the LOS setting. Part Two provides recommendations for clarifying roles and expectations and presents a model for organizing discussion. Part Tree suggests techniques for eliciting active crew participation and in-depth analysis and evaluation. Finally, in Part Four, these techniques are organized according to the facilitation model. Examples of how to effectively use the techniques are provided throughout, including strategies to try when the debriefing objectives are not being fully achieved.

  19. Facilitating Transfer in College Reading Programs.

    ERIC Educational Resources Information Center

    Nist, Sherrie; Simpson, Michele L.

    1987-01-01

    Gives three activities--journal writing, microteaching partners, and the PLAE model (planning, listing, activating, and evaluating)--that can facilitate learner independence and transfer of efficient and effective study strategies in college developmental reading programs. (NKA)

  20. Web-based medical facilitators in medical tourism: the third party in decision-making.

    PubMed

    Wagle, Suchitra

    2013-01-01

    The emergence of web-based medical tourism facilitators (MTFs) has added a new dimension to the phenomenon of cross-border travel. These facilitators are crucial connectors between foreign patients and host countries. They help patients navigate countries, doctors and specialties. However, little attention has been paid to the authenticity of information displayed on the facilitators' web portals, and whether they follow ethical guidelines and standards. This paper analyses the available information on MTF portals from an ethics perspective. It compares 208 facilitators across 47 countries for the services offered. Data were collected from the databases of the Medical Tourism Association and World Medical Resources. India was the most common destination country linked to 81 facilitators. The five countries with the maximum number of facilitators were the USA, the UK, India, Canada and Poland. This paper identifies concerns regarding the information displayed about patients' safety, and the maintenance of confidentiality. There is a need to develop ethical standards for this field.

  1. Ankle-brachial index and extent of atherosclerosis in patients from the Middle East (the AGATHA-ME study): a cross-sectional multicenter study.

    PubMed

    El-Menyar, Ayman; Amin, Haitham; Rashdan, Ibrahim; Souliman, Kadhim; Deleu, Dirk; Saadat, Kamran; Al Mahmeed, Wael; Bakir, Sharif; Wasif, Adel; Ben Brek, Azan; Bazargani, Nooshin; Ahmed Abdel Aziz; Singh, Rajvir; Hatou, Iman; Mahmoud, Hisham; Al Suwaidi, Jassim

    2009-01-01

    To assess the extent of atherothrombosis and the use of the ankle-brachial index (ABI) in populations from the Middle East, we conducted a multicenter study similar to AGATHA (a Global Atherothrombosis Assessment), AGATHA-ME, which included 1341 patients from 18 centers from 5 countries (United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman). Patients were assigned to 2 groups: the with-disease and at-risk groups. Abnormal ABI (< or =0.9) was seen in 31.5% of at-risk patients and 28.2% of with-disease patients. Patients with peripheral arterial disease had the highest frequency of abnormal ABI (77.6%), with 97.8 negative predictive value. The AGATHA-ME study confirms that atherothrombosis disease often occurs at more than 1 site. The ABI is related to the risk factor profile and to the site and extent of atherothrombosis. Gender and diabetes mellitus are associated with the worst parameters.

  2. A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.

    PubMed

    Del Favero, A; Menichetti, F; Martino, P; Bucaneve, G; Micozzi, A; Gentile, G; Furno, P; Russo, D; D'Antonio, D; Ricci, P; Martino, B; Mandelli, F

    2001-10-15

    In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

  3. An International Multicenter Study Assessing the Role of Ethnicity on Variation of Lumbar Facet Joint Orientation and the Occurrence of Degenerative Spondylolisthesis in Asia Pacific: A Study from the AOSpine Asia Pacific Research Collaboration Consortium.

    PubMed

    Williams, Richard; Cheung, Jason Pui Yin; Goss, Ben; Rajasekaran, Shanmuganathan; Kawaguchi, Yoshiharu; Acharya, Shankar; Kawakami, Mamoru; Satoh, Shigenobu; Chen, Wen-Jer; Park, Chun-Kun; Lee, Chong-Suh; Foocharoen, Thanit; Nagashima, Hideki; Kuh, Sunguk; Zheng, Zhaomin; Condor, Richard; Ito, Manabu; Iwasaki, Motoki; Jeong, Je Hoon; Luk, Keith D K; Prijambodo, Bambang; Rege, Amol; Jahng, Tae-Ahn; Luo, Zhuojing; Tassanawipas, Warat; Acharya, Narayana; Pokharel, Rohit; Shen, Yong; Ito, Takui; Zhang, Zhihai; Aithala P, Janardhana; Kumar, Gomatam Vijay; Jabir, Rahyussalim Ahmad; Basu, Saumyajit; Li, Baojun; Moudgil, Vishal; Sham, Phoebe; Samartzis, Dino

    2016-02-01

    joint orientation in the majority of cases of DS in the Asia-Pacific region. Findings from this study may facilitate future comparative studies in other multiethnic populations. An understanding of ethnic variability may assist in identifying those patients at risk of postsurgical development or progression of DS. This study also serves as a model for large-scale multicenter studies across different ethnic groups and cultural boundaries in Asia.

  4. Secured web-based video repository for multicenter studies

    PubMed Central

    Yan, Ling; Hicks, Matt; Winslow, Korey; Comella, Cynthia; Ludlow, Christy; Jinnah, H. A; Rosen, Ami R; Wright, Laura; Galpern, Wendy R; Perlmutter, Joel S

    2015-01-01

    Background We developed a novel secured web-based dystonia video repository for the Dystonia Coalition, part of the Rare Disease Clinical Research network funded by the Office of Rare Diseases Research and the National Institute of Neurological Disorders and Stroke. A critical component of phenotypic data collection for all projects of the Dystonia Coalition includes a standardized video of each participant. We now describe our method for collecting, serving and securing these videos that is widely applicable to other studies. Methods Each recruiting site uploads standardized videos to a centralized secured server for processing to permit website posting. The streaming technology used to view the videos from the website does not allow downloading of video files. With appropriate institutional review board approval and agreement with the hosting institution, users can search and view selected videos on the website using customizable, permissions-based access that maintains security yet facilitates research and quality control. Results This approach provides a convenient platform for researchers across institutions to evaluate and analyze shared video data. We have applied this methodology for quality control, confirmation of diagnoses, validation of rating scales, and implementation of new research projects. Conclusions We believe our system can be a model for similar projects that require access to common video resources. PMID:25630890

  5. Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study.

    PubMed

    Pope, Whitney B; Qiao, Xin Joe; Kim, Hyun J; Lai, Albert; Nghiemphu, Phioanh; Xue, Xi; Ellingson, Benjamin M; Schiff, David; Aregawi, Dawit; Cha, Soonmee; Puduvalli, Vinay K; Wu, Jing; Yung, Wai-Kwan A; Young, Geoffrey S; Vredenburgh, James; Barboriak, Dan; Abrey, Lauren E; Mikkelsen, Tom; Jain, Rajan; Paleologos, Nina A; Rn, Patricia Lada; Prados, Michael; Goldin, Jonathan; Wen, Patrick Y; Cloughesy, Timothy

    2012-07-01

    We have tested the predictive value of apparent diffusion coefficient (ADC) histogram analysis in stratifying progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients with recurrent glioblastoma multiforme (GBM) from the multi-center BRAIN study. Available MRI's from patients enrolled in the BRAIN study (n = 97) were examined by generating ADC histograms from areas of enhancing tumor on T1 weighted post-contrast images fitted to a two normal distribution mixture curve. ADC classifiers including the mean ADC from the lower curve (ADC-L) and the mean lower curve proportion (LCP) were tested for their ability to stratify PFS and OS by using Cox proportional hazard ratios and the Kaplan-Meier method with log-rank test. Mean ADC-L was 1,209 × 10(-6)mm(2)/s ± 224 (SD), and mean LCP was 0.71 ± 0.23 (SD). Low ADC-L was associated with worse outcome. The hazard ratios for 6-month PFS, overall PFS, and OS in patients with less versus greater than mean ADC-L were 3.1 (95 % confidence interval: 1.6, 6.1; P = 0.001), 2.3 (95 % CI: 1.3, 4.0; P = 0.002), and 2.4 (95 % CI: 1.4, 4.2; P = 0.002), respectively. In patients with ADC-L <1,209 and LCP >0.71 versus ADC-L >1,209 and LCP <0.71, there was a 2.28-fold reduction in the median time to progression, and a 1.42-fold decrease in the median OS. The predictive value of ADC histogram analysis, in which low ADC-L was associated with poor outcome, was confirmed in bevacizumab-treated patients with recurrent GBM in a post hoc analysis from the multi-center (BRAIN) study.

  6. Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: a multicenter longitudinal study.

    PubMed

    Borrelli, Silvio; Minutolo, Roberto; De Nicola, Luca; De Simone, Emanuele; De Simone, Walter; Zito, Bruno; Guastaferro, Pasquale; Nigro, Filippo; Iulianiello, Giuseppe; Credendino, Olga; Bassi, Antonio; Leone, Luigi; Capuano, Maria; Auricchio, Maria Rita; Conte, Giuseppe

    2014-10-01

    Chronic inflammation is widely diffuse in maintenance hemodialysis (MHD) patients and is associated with poor survival. Hemodiafiltration with endogenous reinfusion (HFR) is a dialysis technique, highly biocompatible, able to adsorb proinflammatory cytokines and to decrease amino acids and antioxidants loss. These features could be helpful in MHD patients affected by idiopathic chronic inflammation, but this issue remains to be elucidated. We performed a multicenter longitudinal study to assess the effect of the switching from bicarbonate HD to HFR in patients with serum C-reactive Protein (CRP) > 5 mg/L coupled with albumin <4.0 g/dL in the last 6 months. We enrolled 24/176 (14%) patients, of which 20 patients were assessed at 4 months and 18 completed the study. We excluded 11 patients with evident causes of inflammation. At baseline, serum levels of CRP (18.7[7.0-39.4] mg/L) and albumin (3.5[3.3-3.7] g/dL) were significantly correlated (r = -0.49; P = 0.028). The effect on CRP and albumin was almost evident in the first 4 months and remained stable until to eighth month. A strict correlation (R = -0.49; 0.040) between percentage change of CRP (-35%) and albumin (+14%) after 8 months of HFR. These effects were associated with the reduction of IL-6, IL-1β, and TNF-α and the increment of pre-albumin and leptin, whereas the serum levels of Branched Chain Amino Acid (BCAA) remained unchanged. In MHD patients affected by idiopathic chronic inflammation the switching from BHD to HFR is associated with improvement of inflammation. Whether these favorable effects may modify the outcomes of these high-risk patients needs to be confirmed by studies ad hoc.

  7. Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: correlation with coagulopathy

    PubMed Central

    Matijevic, Nena; Wang, Yao-Wei W.; Wade, Charles E.; Holcomb, John B.; Cotton, Bryan A.; Schreiber, Martin A.; Muskat, Peter; Fox, Erin E.; del Junco, Deborah J.; Cardenas, Jessica C.; Rahbar, Mohammad H.; Cohen, Mitchell Jay

    2014-01-01

    Background Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. Methods As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). Conclusions Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding. PMID:25086657

  8. A multicenter study of diet quality on birth weight and gestational age in infants of HIV-infected women.

    PubMed

    Miller, Tracie L; Jacobson, Denise L; Somarriba, Gabriel; Neri, Daniela; Kurtz-Vraney, Joy; Graham, Patricia; Gillman, Matthew W; Landy, David C; Siminski, Suzanne; Butler, Laurie; Rich, Kenneth C; Hendricks, Kristy; Ludwig, David A

    2016-11-08

    We determined factors associated with diet quality and assessed the relationship between diet quality, birth weight, and gestational age in a prospective national multicenter cohort study. We evaluated diet quality with the Healthy Eating Index (HEI, scale 0-100) in the third trimester of pregnancy with three 24-hr multiple-pass dietary recalls in 266 HIV+ women enrolled in the Pediatric HIV/AIDS Cohort Study. Covariates included demographics, food security, pre-pregnancy body mass index, HIV disease severity, substance use, and antiretroviral exposures. A two-stage multivariate process using classification and regression trees (CART) followed by multiple regression described HEI tendencies, controlled possible confounding effects, and examined the association of HEI with birth weight and gestational age. To assess the stability of the CART solution, both the HEI 2005 and 2010 were evaluated. The mean HEI scores were 56.1 and 47.5 for the 2005 and 2010 HEI, respectively. The first-stage CART analysis examined the relationship between HEI and covariates. Non-US born versus US-born mothers had higher HEI scores (15-point difference, R(2)  = 0.28). There was a secondary partition due to alcohol/cigarette/illicit drug usage (3.5-point difference, R(2)  = 0.03) among US-born women. For the second-stage CART adjusted multiple regression, birth weight z-score was positively related to HEI 2005 and 2010 (partial r's > 0.13, P's ≤ 0.0398), but not gestational age (r = 0.00). We conclude that diet quality among HIV+ women is associated with higher birth weight. Despite the influence of a large cultural effect and poor prenatal behaviors, interventions to improve diet in HIV+ women may help to increase birth weight.

  9. Microcurrent electrical nerve stimulation facilitates regrowth of mouse soleus muscle.

    PubMed

    Ohno, Yoshitaka; Fujiya, Hiroto; Goto, Ayumi; Nakamura, Ayane; Nishiura, Yuka; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Goto, Katsumasa

    2013-01-01

    Microcurrent electrical nerve stimulation (MENS) has been used to facilitate recovery from skeletal muscle injury. However, the effects of MENS on unloading-associated atrophied skeletal muscle remain unclear. Effects of MENS on the regrowing process of unloading-associated atrophied skeletal muscle were investigated. Male C57BL/6J mice (10-week old) were randomly assigned to untreated normal recovery (C) and MENS-treated (M) groups. Mice of both groups are subjected to continuous hindlimb suspension (HS) for 2 weeks followed by 7 days of ambulation recovery. Mice in M group were treated with MENS for 60 min 1, 3, and 5 days following HS, respectively, under anesthesia. The intensity, the frequency, and the pulse width of MENS were set at 10 μA, 0.3 Hz, and 250 msec, respectively. Soleus muscles were dissected before and immediately after, 1, 3 and 7 days after HS. Soleus muscle wet weight and protein content were decreased by HS. The regrowth of atrophied soleus muscle in M group was faster than that in C group. Decrease in the reloading-induced necrosis of atrophied soleus was facilitated by MENS. Significant increases in phosphorylated levels of p70 S6 kinase and protein kinase B (Akt) in M group were observed, compared with C group. These observations are consistent with that MENS facilitated regrowth of atrophied soleus muscle. MENS may be a potential extracellular stimulus to activate the intracellular signals involved in protein synthesis.

  10. Quality control for quantitative multicenter whole-body PET/MR studies: A NEMA image quality phantom study with three current PET/MR systems

    SciTech Connect

    Boellaard, Ronald; Rausch, Ivo; Beyer, Thomas; Delso, Gaspar; Yaqub, Maqsood; Quick, Harald H.; Sattler, Bernhard

    2015-10-15

    Purpose: Integrated positron emission tomography/magnetic resonance (PET/MR) systems derive the PET attenuation correction (AC) from dedicated MR sequences. While MR-AC performs reasonably well in clinical patient imaging, it may fail for phantom-based quality control (QC). The authors assess the applicability of different protocols for PET QC in multicenter PET/MR imaging. Methods: The National Electrical Manufacturers Association NU 2 2007 image quality phantom was imaged on three combined PET/MR systems: a Philips Ingenuity TF PET/MR, a Siemens Biograph mMR, and a GE SIGNA PET/MR (prototype) system. The phantom was filled according to the EANM FDG-PET/CT guideline 1.0 and scanned for 5 min over 1 bed. Two MR-AC imaging protocols were tested: standard clinical procedures and a dedicated protocol for phantom tests. Depending on the system, the dedicated phantom protocol employs a two-class (water and air) segmentation of the MR data or a CT-based template. Differences in attenuation- and SUV recovery coefficients (RC) are reported. PET/CT-based simulations were performed to simulate the various artifacts seen in the AC maps (μ-map) and their impact on the accuracy of phantom-based QC. Results: Clinical MR-AC protocols caused substantial errors and artifacts in the AC maps, resulting in underestimations of the reconstructed PET activity of up to 27%, depending on the PET/MR system. Using dedicated phantom MR-AC protocols, PET bias was reduced to −8%. Mean and max SUV RC met EARL multicenter PET performance specifications for most contrast objects, but only when using the dedicated phantom protocol. Simulations confirmed the bias in experimental data to be caused by incorrect AC maps resulting from the use of clinical MR-AC protocols. Conclusions: Phantom-based quality control of PET/MR systems in a multicenter, multivendor setting may be performed with sufficient accuracy, but only when dedicated phantom acquisition and processing protocols are used for

  11. Facilitating tolerance of delayed reinforcement during functional communication training.

    PubMed

    Fisher, W W; Thompson, R H; Hagopian, L P; Bowman, L G; Krug, A

    2000-01-01

    Few clinical investigations have addressed the problem of delayed reinforcement. In this investigation, three individuals whose destructive behavior was maintained by positive reinforcement were treated using functional communication training (FCT) with extinction (EXT). Next, procedures used in the basic literature on delayed reinforcement and self-control (reinforcer delay fading, punishment of impulsive responding, and provision of an alternative activity during reinforcer delay) were used to teach participants to tolerate delayed reinforcement. With the first case, reinforcer delay fading alone was effective at maintaining low rates of destructive behavior while introducing delayed reinforcement. In the second case, the addition of a punishment component reduced destructive behavior to near-zero levels and facilitated reinforcer delay fading. With the third case, reinforcer delay fading was associated with increases in masturbation and head rolling, but prompting and praising the individual for completing work during the delay interval reduced all problem behaviors and facilitated reinforcer delay fading.

  12. Trajectories of Marijuana Use among HIV-seropositive and HIV-seronegative MSM in the Multicenter AIDS Cohort Study (MACS), 1984-2013.

    PubMed

    Okafor, Chukwuemeka N; Cook, Robert L; Chen, Xinguang; Surkan, Pamela J; Becker, James T; Shoptaw, Steve; Martin, Eileen; Plankey, Michael W

    2017-04-01

    To construct longitudinal trajectories of marijuana use in a sample of men who have sex with men living with or at-risk for HIV infection. We determined factors associated with distinct trajectories of use as well as those that serve to modify the course of the trajectory. Data were from 3658 [1439 HIV-seropositive (HIV+) and 2219 HIV-seronegative (HIV-)] participants of the Multicenter AIDS Cohort Study. Frequency of marijuana use was obtained semiannually over a 29-year period (1984-2013). Group-based trajectory models were used to identify the trajectories and to determine predictors and modifiers of the trajectories over time. Four distinct trajectories of marijuana use were identified: abstainer/infrequent (65 %), decreaser (13 %), increaser (12 %) and chronic high (10 %) use groups. HIV+ status was significantly associated with increased odds of membership in the decreaser, increaser and chronic high use groups. Alcohol, smoking, stimulant and other recreational drug use were associated with increasing marijuana use across all four trajectory groups. Antiretroviral therapy use over time was associated with decreasing marijuana use in the abstainer/infrequent and increaser trajectory groups. Having a detectable HIV viral load was associated with increasing marijuana use in the increaser group only. Future investigations are needed to determine whether long-term patterns of use are associated with adverse consequences especially among HIV+ persons.

  13. Facilitation as a ubiquitous driver of biodiversity.

    PubMed

    McIntire, Eliot J B; Fajardo, Alex

    2014-01-01

    Models describing the biotic drivers that create and maintain biological diversity within trophic levels have focused primarily on negative interactions (i.e. competition), leaving marginal room for positive interactions (i.e. facilitation). We show facilitation to be a ubiquitous driver of biodiversity by first noting that all species use resources and thus change the local biotic or abiotic conditions, altering the available multidimensional niches. This can cause a shift in local species composition, which can cause an increase in beta, and sometimes alpha, diversity. We show that these increases are ubiquitous across ecosystems. These positive effects on diversity occur via a broad host of disparate direct and indirect mechanisms. We identify and unify several of these facilitative mechanisms and discuss why it has been easy to underappreciate the importance of facilitation. We show that net positive effects have a long history of being considered ecologically or evolutionarily unstable, and we present recent evidence of its potential stability. Facilitation goes well beyond the common case of stress amelioration and it probably gains importance as community complexity increases. While biodiversity is, in part, created by species exploiting many niches, many niches are available to exploit only because species create them.

  14. Facilitation: An Essential Ingredient in Online Coursework

    NASA Astrophysics Data System (ADS)

    Ristvey, J.; Bogner, D.

    2003-12-01

    Mid-continent Research for Education and Learning (McREL) partnered with the Colorado School of Mines (CSM) to offer the ESSEA Earth System Science Online Course for Middle School Teachers during the 2002-2003 school year. During the two semesters that the course was offered, we were able to retain 75% of our enrollees. We found that course facilitation was the key ingredient in retaining this large number of students-who are not only scattered across the U.S., but around the world-in a rigorous online course. In this poster session, we will share what we have learned about online facilitation as part of this course, and how this knowledge might translate into other online coursework. Online facilitation begins as soon as a student enrolls in the course. When a student registers online or at CSM, McREL receives notification and then sends course materials and e-mail and written confirmation to the enrollee within 24 hours. This sets the tone for the type of communications that students can expect during the 16-week course. McREL facilitators know how time consuming monitoring participant progress can be, but feel strongly about its importance when facilitating learners who are working in small groups and are completing independent research. Timely monitoring of discussion spaces and e-mail messages is essential to maintaining a high student-retention rate. Kearsley (2000) confirms this when he states that, "the most important role of the instructor in online classes is to ensure that there is a high degree of interactivity and participation." In the ESSEA courses, the isolation of students working independently on classroom applications and reflection is balanced with group construction of interactions and causal chains. Each step of the way facilitators use guided questioning in group discussion sessions and serve as a mentor when participants develop individualized classroom assignments, giving participants the opportunity to apply what they have learned in a

  15. Oral mifepristone 600 mg and vaginal gemeprost for mid-trimester induction of abortion. An open multicenter study. UK Multicenter Study Group.

    PubMed

    1997-12-01

    This open multicenter study was performed in 20 hospital gynecological units in the UK. The effects of 600 mg oral mifepristone as pretreatment to vaginal prostaglandin induction of second trimester abortion was studied in 267 women. The primary efficacy variable was the abortion induction interval, defined as the time taken to expel the fetus from the time of administration of the first prostaglandin pessary. Induction was commenced 36 to 48 hours following mifepristone intake. The mean abortion induction interval was 7 h. A total of 81.9% of women aborted within 12 h. There was a significant relationship between abortion induction interval and age of gestation, and a significant inverse relationship between abortion induction interval and parity. Vomiting, pelvic pain, and nausea were the most frequently reported adverse events. Two patients required transfusion and one patient with a uterine scar from a previous cesarean section suffered a ruptured uterus and hysterotomy.

  16. The Burden of Eclampsia: Results from a Multicenter Study on Surveillance of Severe Maternal Morbidity in Brazil

    PubMed Central

    Giordano, Juliana C.; Parpinelli, Mary A.; Cecatti, Jose G.; Haddad, Samira M.; Costa, Maria L.; Surita, Fernanda G.; Pinto e Silva, Joao L.; Sousa, Maria H.

    2014-01-01

    Objective Maternal mortality (MM) is a core indicator of disparities in women’s rights. The study of Near Miss cases is strategic to identifying the breakdowns in obstetrical care. In absolute numbers, both MM and occurrence of eclampsia are rare events. We aim to assess the obstetric care indicators and main predictors for severe maternal outcome from eclampsia (SMO: maternal death plus maternal near miss). Methods Secondary analysis of a multicenter, cross-sectional study, including 27 centers from all geographic regions of Brazil, from 2009 to 2010. 426 cases of eclampsia were identified and classified according to the outcomes: SMO and non-SMO. We classified facilities as coming from low- and high-income regions and calculated the WHO’s obstetric health indicators. SPSS and Stata softwares were used to calculate the prevalence ratios (PR) and respective 95% confidence interval (CI) to assess maternal characteristics, clinical and obstetrical history, and access to health services as predictors for SMO, subsequently correlating them with the corresponding perinatal outcomes, also applying multiple regression analysis (adjusted for cluster effect). Results Prevalence of and mortality indexes for eclampsia in higher and lower income regions were 0.2%/0.8% and 8.1%/22%, respectively. Difficulties in access to health care showed that ICU admission (adjPR 3.61; 95% CI 1.77–7.35) and inadequate monitoring (adjPR 2.31; 95% CI 1.48–3.59) were associated with SMO. Conclusions Morbidity and mortality associated with eclampsia were high in Brazil, especially in lower income regions. Promoting quality maternal health care and improving the availability of obstetric emergency care are essential actions to relieve the burden of eclampsia. PMID:24825164

  17. Severe Septic Patients with Mitochondrial DNA Haplogroup JT Show Higher Survival Rates: A Prospective, Multicenter, Observational Study

    PubMed Central

    Martín, María M.; López-Gallardo, Esther; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Borreguero-León, Juan María; Jiménez, Alejandro; Montoya, Julio; Ruiz-Pesini, Eduardo

    2013-01-01

    Objective In a previous cohort study (n=96), we found an association between mitochondrial (mt) DNA haplogroup JT and increased survival of severe septic patients, after controlling for age and serum lactic acid levels. The aim of this research was to increase the predictive accuracy and to control for more confounder variables in a larger cohort (n=196) of severe septic patients, to confirm whether mtDNA haplogroup JT influences short and medium-term survival in these patients. Methods We conducted a prospective, multicenter, observational study in six Spanish Intensive Care Units. We determined 30-day and 6-month survival and mtDNA haplogroup in this second cohort of 196 patients and in the global cohort (first and second cohorts combined) with 292 severe septic patients. Multiple logistic regression and Cox regression analyses were used to test for the association of mtDNA haplogroups JT with survival at 30-days and 6-months, controlling for age, sex, serum interleukin-6 levels and SOFA score. Results Logistic and Cox regression analyses showed no differences in 30-day and 6-month survival between patients with mtDNA haplogroup JT and other haplogroups in the first cohort (n=96). In the second cohort (n=196), these analyses showed a trend to higher 30-day and 6-month survival in those with haplogroup JT. In the global cohort (n=292), logistic and Cox regression analyses showed higher 30-day and 6-month survival for haplogroup JT. There were no significant differences between J and T sub-haplogroups in 30-day and 6-month survival. Conclusions The global cohort study (first and second cohorts combined), the largest to date reporting on mtDNA haplogroups in septic patients, confirmed that haplogroup JT patients showed increased 30-day and 6-month survival. This finding may be due to single nucleotide polymorphism defining the whole haplogroup JT and not separately for J or T sub-haplogroups. PMID:24069186

  18. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

    PubMed Central

    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  19. Inventory of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae in France as Assessed by a Multicenter Study.

    PubMed

    Robin, F; Beyrouthy, R; Bonacorsi, S; Aissa, N; Bret, L; Brieu, N; Cattoir, V; Chapuis, A; Chardon, H; Degand, N; Doucet-Populaire, F; Dubois, V; Fortineau, N; Grillon, A; Lanotte, P; Leyssene, D; Patry, I; Podglajen, I; Recule, C; Ros, A; Colomb-Cotinat, M; Ponties, V; Ploy, M C; Bonnet, R

    2017-03-01

    The objective of this study was to perform an inventory of the extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae isolates responsible for infections in French hospitals and to assess the mechanisms associated with ESBL diffusion. A total of 200 nonredundant ESBL-producing Enterobacteriaceae strains isolated from clinical samples were collected during a multicenter study performed in 18 representative French hospitals. Antibiotic resistance genes were identified by PCR and sequencing experiments. The clonal relatedness between isolates was investigated by the use of the DiversiLab system. ESBL-encoding plasmids were compared by PCR-based replicon typing and plasmid multilocus sequence typing. CTX-M-15, CTX-M-1, CTX-M-14, and SHV-12 were the most prevalent ESBLs (8% to 46.5%). The three CTX-M-type EBSLs were significantly observed in Escherichia coli (37.1%, 24.2%, and 21.8%, respectively), and CTX-M-15 was the predominant ESBL in Klebsiella pneumoniae (81.1%). SHV-12 was associated with ESBL-encoding Enterobacter cloacae strains (37.9%). qnrB, aac(6')-Ib-cr, and aac(3)-II genes were the main plasmid-mediated resistance genes, with prevalences ranging between 19.5% and 45% according to the ESBL results. Molecular typing did not identify wide clonal diffusion. Plasmid analysis suggested the diffusion of low numbers of ESBL-encoding plasmids, especially in K. pneumoniae and E. cloacae However, the ESBL-encoding genes were observed in different plasmid replicons according to the bacterial species. The prevalences of ESBL subtypes differ according to the Enterobacteriaceae species. Plasmid spread is a key determinant of this epidemiology, and the link observed between the ESBL-encoding plasmids and the bacterial host explains the differences observed in the Enterobacteriaceae species.

  20. Inflammatory arthritis in patients with myelodysplastic syndromes: a multicenter retrospective study and literature review of 68 cases.

    PubMed

    Mekinian, Arsène; Braun, Thorsten; Decaux, Olivier; Falgarone, Géraldine; Toussirot, Eric; Raffray, Loic; Omouri, Mohamed; Gombert, Bruno; De Wazieres, Benoit; Buchdaul, Anne-Laure; Ziza, Jean-Marc; Launay, David; Denis, Guillaume; Madaule, Serge; Rose, Christian; Grignano, Eric; Fenaux, Pierre; Fain, Olivier

    2014-01-01

    We describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study. Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69-81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2-6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions. The median time between the diagnoses of arthritis and MDS was 10 months [6-42], with a median articular symptom duration of 3 months [2-8]. The diagnosis of both diseases was concomitant in 6 cases (27%); arthritis preceded MDS in 12 cases (55%), and occurred after MDS in 4 (18%). While the number of swollen and tender joints significantly decreased during follow-up, as did the median DAS28-CRP (from 4.3 [3.8-4.6] at baseline to 2.9 [1.75-3.3]; p < 0.05), CRP remained elevated (CRP >20 mg/L) in 8 patients (42%). Nevertheless, radiographic progression and new ACPA positivity were not observed during a median follow-up of 29 months [9-76]. While most of the patients were treated with steroids (n = 16) for arthritis, additional treatment was administered in only 4 patients (hydroxychloroquine, n = 2; sulfasalazine [Salazopyrin] and etanercept, n = 1, respectively). Eleven patients died during follow-up from acute myeloid leukemia (n = 5); infections (n = 3); or cerebral bleeding, cardiorespiratory failure, or undetermined cause (n = 1, respectively). Inflammatory arthritis associated with MDS can have various presentations and is often seronegative and nonerosive. Steroids alone are the most common treatment in MDS-associated arthritis, but that treatment is insufficient to control arthritis. Steroid-sparing strategies need to be identified.

  1. Open Surgical versus Minimal Invasive Necrosectomy of the Pancreas—A Retrospective Multicenter Analysis of the German Pancreatitis Study Group

    PubMed Central

    Rasch, Sebastian; Phillip, Veit; Reichel, Stephanie; Rau, Bettina; Zapf, Christian; Rosendahl, Jonas; Halm, Ulrich; Zachäus, Markus; Müller, Martin; Kleger, Alexander; Neesse, Albrecht; Hampe, Jochen; Ellrichmann, Mark; Rückert, Felix; Strauß, Peter; Algül, Hana

    2016-01-01

    Background Necrotising pancreatitis, and particularly infected necrosis, are still associated with high morbidity and mortality. Since 2011, a step-up approach with lower morbidity rates compared to initial open necrosectomy has been established. However, mortality and complication rates of this complex treatment are hardly studied thereafter. Methods The German Pancreatitis Study Group performed a multicenter, retrospective study including 220 patients with necrotising pancreatitis requiring intervention, treated at 10 hospitals in Germany between January 2008 and June 2014. Data were analysed for the primary endpoints "severe complications" and "mortality" as well as secondary endpoints including "length of hospital stay", "follow up", and predisposing or prognostic factors. Results Of all patients 13.6% were treated primarily with surgery and 86.4% underwent a step-up approach. More men (71.8%) required intervention for necrotising pancreatitis. The most frequent etiology was biliary (41.4%) followed by alcohol (29.1%). Compared to open necrosectomy, the step-up approach was associated with a lower number of severe complications (primary composite endpoint including sepsis, persistent multiorgan dysfunction syndrome (MODS) and erosion bleeding: 44.7% vs. 73.3%), lower mortality (10.5% vs. 33.3%) and lower rates of diabetes mellitus type 3c (4.7% vs. 33.3%). Low hematocrit and low blood urea nitrogen at admission as well as a history of acute pancreatitis were prognostic for less complications in necrotising pancreatitis. A combination of drainage with endoscopic necrosectomy resulted in the lowest rate of severe complications. Conclusion A step-up approach starting with minimal invasive drainage techniques and endoscopic necrosectomy results in a significant reduction of morbidity and mortality in necrotising pancreatitis compared to a primarily surgical intervention. PMID:27668746

  2. Frequency of atrial tachyarrhythmias in patients treated by cardiac resynchronization (from the Prospective, Multicenter Mona Lisa Study).

    PubMed

    Marijon, Eloi; Jacob, Sophie; Mouton, Elisabeth; Defaye, Pascal; Piot, Olivier; Delarche, Nicolas; Dennetiere, Stéphane; Galley, Daniel; Le Franc, Pierre; Appl, Ursula; Guyomar, Yves; Albenque, Jean Paul; Chevalier, Philippe; Boveda, Serge

    2010-09-01

    The continuous measurement of sustained atrial tachyarrhythmia (AT) is now possible with some permanently implanted devices. Data on this subject remain controversial. The aim of this study was to evaluate the incidence of sustained AT in patients treated with cardiac resynchronization therapy using pacemakers without backup defibrillators (CRT-P), within the first year after implantation, using strict definition criteria for sustained AT and a systematic review of all high-quality electrographically recorded episodes. The Mona Lisa study was a prospective, multicenter, cohort study carried out from February 2004 to February 2006, with a 12-month follow-up period. Sustained AT was defined as an episode lasting > or =5 minutes; episodes were confirmed by a systematic review of electrograms in the whole study population. Of the 198 patients who underwent CRT-P device implantation and were enrolled in the study, 173 were in stable sinus rhythm at baseline and were included in the analysis (mean age 70 +/- 9 years, 66% men, 91% in New York Heart Association class III, mean QRS duration 164 +/- 26 ms, mean left ventricular ejection fraction 25 +/- 7%). During a mean follow-up period of 9.9 +/- 3.6 months, 34 patients experienced > or =1 episode of sustained AT, for an incidence rate of 27.5% (95% confidence interval 18.2 to 36.7). Only a history of AT was independently associated with the occurrence of sustained AT within the 12 months after CRT-P device implantation (hazard ratio 2.3, 95% confidence interval 1.2 to 4.4, p = 0.02). In conclusion, this first prospective electrogram-based evaluation of AT incidence demonstrated that 27% of patients developed > or =1 episode of sustained AT lasting > or =5 minutes in the 12 months after CRT-P device implantation.

  3. Patient recruitment into a multicenter randomized clinical trial for kidney disease: report of the focal segmental glomerulosclerosis clinical trial (FSGS CT).

    PubMed

    Ferris, Maria; Norwood, Victoria; Radeva, Milena; Gassman, Jennifer J; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

    2013-02-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology.

  4. Patient Recruitment into a Multicenter Randomized Clinical Trial for Kidney Disease: Report of the Focal Segmental Glomerulosclerosis Clinical Trial (FSGS CT)

    PubMed Central

    Ferris, Maria; Norwood, Victoria; Radeva, Milena; Al-Uzri, Amira; Askenazi, David; Matoo, Tej; Pinsk, Maury; Sharma, Amita; Smoyer, William; Stults, Jenna; Vyas, Shefali; Weiss, Robert; Gipson, Debbie; Kaskel, Frederick; Friedman, Aaron; Moxey-Mims, Marva; Trachtman, Howard

    2015-01-01

    We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. PMID:23399084

  5. Caregivers Lack of Disclosure Skills Delays Disclosure to Children with Perinatal HIV in Resource-Limited Communities: Multicenter Qualitative Data from South Africa and Botswana

    PubMed Central

    2016-01-01

    To promote the appropriate implementation of procedures for health disclosure to children, it is important to understand the reasons why caregivers delay the disclosure of healthcare information to children. This paper explored the views of caregivers on what makes disclosure to children with perinatal acquired HIV (PAH) difficult and what could make disclosure in these cases easier. Data were collected using focus group interviews with caregivers who were purposely selected from a multicenter study conducted in Botswana and South Africa. Forty-seven nondisclosed caregivers of children between 5 and 18 years who were receiving ART were interviewed. Caregivers felt that children should be told of their HIV-positive status despite the fact that none had disclosed this information to the children. The caregivers reported lack of disclosure skills but believed they were primarily responsible for disclosure to children and required support from healthcare workers (HCWs) during the disclosure process. They believed that counseling on how to approach disclosure and training on when and how to disclose will make the disclosure process easier. HCWs have a crucial role to play in promoting disclosure to perinatally infected children. The development of appropriate disclosure guidelines and training for HCWs will facilitate disclosure to children. PMID:28018673

  6. The mechanism of facilitated cell membrane resealing.

    PubMed

    Togo, T; Alderton, J M; Bi, G Q; Steinhardt, R A

    1999-03-01

    Disruption of the plasma membrane evokes an exocytotic response that is required for rapid membrane resealing. We show here in Swiss 3T3 fibroblasts that a second disruption at the same site reseals more rapidly than the initial wound. This facilitated response of resealing was inhibited by both low external Ca2+ concentration and specific protein kinase C (PKC) inhibitors, bisindolylmaleimide I (BIS) and Gö-6976. In addition, activation of PKC by phorbol ester facilitated the resealing of a first wound. BIS and Gö-6976 suppressed the effect of phorbol ester on resealing rate. Fluorescent dye loss from a FM1-43 pre-labeled endocytotic compartment was used to investigate the relationship between exocytosis, resealing and the facilitation of resealing. Exocytosis of endocytotic compartments near the wounding site was correlated with successful resealing. The destaining did not occur when exocytosis and resealing were inhibited by low external Ca2+ concentration or by injected tetanus toxin. When the dye loaded cells were wounded twice, FM1-43 destaining at the second wound was less than at the first wound. Less destaining was also observed in cells pre-treated with phorbol ester, suggesting newly formed vesicles, which were FM1-43 unlabeled, were exocytosed in the resealing at repeated woundings. Facilitation was also blocked by brefeldin A (BFA), a fungal metabolite that inhibits vesicle formation at the Golgi apparatus. Lowering the temperature below 20 degrees C also blocked facilitation as expected from a block of Golgi function. BFA had no effect on the resealing rate of an initial wound. The facilitation of the resealing by phorbol ester was blocked by pre-treatment with BFA. These results suggest that at first wounding the cell used the endocytotic compartment to add membrane necessary for resealing. At a second wounding, PKC, activated by Ca2+ entry at the first wound, stimulated vesicle formation from the Golgi apparatus, resulting in more rapid resealing

  7. Factors for Effective Facilitator Training Evaluation.

    DTIC Science & Technology

    1996-09-01

    34 Journal of Personality and Social Psychology 59(6): 1216-1229( 1990 ). Hackman , J. Richard and Greg R. Oldham. Work Redesign. Reading MA: Addison...the Effect of Response Distortion On Those Validities," Journal of Applied Psychology 75: 581-595 ( 1990 ). "Introduction to Facilitator Training...4 """’. r "- " \\ <*’ -#äJ ^’i&fc^i*^’.-J litSt ... A**" ■ 4? FACTORS FOR EFFECTIVE FACILITATOR TRAINING EVALUATION THESIS Mark I

  8. Facilitated diffusion buffers noise in gene expression.

    PubMed

    Schoech, Armin P; Zabet, Nicolae Radu

    2014-09-01

    Transcription factors perform facilitated diffusion [three-dimensional (3D) diffusion in the cytosol and 1D diffusion on the DNA] when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be represented by a two-state Markov model and that the accelerated target finding due to facilitated diffusion leads to a reduction in both the mRNA and the protein noise.

  9. Facilitated diffusion buffers noise in gene expression

    NASA Astrophysics Data System (ADS)

    Schoech, Armin P.; Zabet, Nicolae Radu

    2014-09-01

    Transcription factors perform facilitated diffusion [three-dimensional (3D) diffusion in the cytosol and 1D diffusion on the DNA] when binding to their target sites to regulate gene expression. Here, we investigated the influence of this binding mechanism on the noise in gene expression. Our results showed that, for biologically relevant parameters, the binding process can be re