A Combination of Amino Acids and Caffeine Enhances Sprint Running Capacity in a Hot, Hypoxic Environment.

PubMed

Eaton, Tom R; Potter, Aaron; Billaut, François; Panchuk, Derek; Pyne, David B; Gore, Christopher J; Chen, Ting-Ting; McQuade, Leon; Stepto, Nigel K

2016-02-01

Heat and hypoxia exacerbate central nervous system (CNS) fatigue. We therefore investigated whether essential amino acid (EAA) and caffeine ingestion attenuates CNS fatigue in a simulated team sport-specific running protocol in a hot, hypoxic environment. Subelite male team sport athletes (n = 8) performed a repeat sprint running protocol on a nonmotorized treadmill in an extreme environment on 4 separate occasions. Participants ingested one of four supplements: a double placebo, 3 mg.kg-1 body mass of caffeine + placebo, 2 x 7 g EAA (Musashi Create)+placebo, or caffeine + EAA before each exercise session using a randomized, double-blind crossover design. Electromyography (EMG) activity and quadriceps evoked responses to magnetic stimulation were assessed from the dominant leg at preexercise, halftime, and postexercise. Central activation ratio (CAR) was used to quantify completeness of quadriceps activation. Oxygenation of the prefrontal cortex was measured via near-infrared spectroscopy. Mean sprint work was higher (M = 174 J, 95% CI [23, 324], p < .05, d = 0.30; effect size, likely beneficial) in the caffeine + EAA condition versus EAAs alone. The decline in EMG activity was less (M = 13%, 95% CI [0, 26]; p < .01, d = 0.58, likely beneficial) in caffeine + EAA versus EAA alone. Similarly, the pre- to postexercise decrement in CAR was significantly less (M = -2.7%, 95% CI [0.4, 5.4]; p < .05, d = 0.50, likely beneficial) when caffeine + EAA were ingested compared with placebo. Cerebral oxygenation was lower (M = -5.6%, 95% CI [1.0, 10.1]; p < .01, d = 0.60, very likely beneficial) in the caffeine + EAA condition compared with LNAA alone. Co-ingestion of caffeine and EAA appears to maintain muscle activation and central drive, with a small improvement in running performance.

Incorporation of extra amino acids in peptide recognition probe to improve specificity and selectivity of an electrochemical peptide-based sensor.

PubMed

Zaitouna, Anita J; Maben, Alex J; Lai, Rebecca Y

2015-07-30

We investigated the effect of incorporating extra amino acids (AA) at the n-terminus of the thiolated and methylene blue-modified peptide probe on both specificity and selectivity of an electrochemical peptide-based (E-PB) HIV sensor. The addition of a flexible (SG)3 hexapeptide is, in particular, useful in improving sensor selectivity, whereas the addition of a highly hydrophilic (EK)3 hexapeptide has shown to be effective in enhancing sensor specificity. Overall, both E-PB sensors fabricated using peptide probes with the added AA (SG-EAA and EK-EAA) showed better specificity and selectivity, especially when compared to the sensor fabricated using a peptide probe without the extra AA (EAA). For example, the selectivity factor recorded in the 50% saliva was ∼2.5 for the EAA sensor, whereas the selectivity factor was 7.8 for both the SG-EAA and EK-EAA sensors. Other sensor properties such as the limit of detection and dynamic range were minimally affected by the addition of the six AA sequence. The limit of detection was 0.5 nM for the EAA sensor and 1 nM for both SG-EAA and EK-EAA sensors. The saturation target concentration was ∼200 nM for all three sensors. Unlike previously reported E-PB HIV sensors, the peptide probe functions as both the recognition element and antifouling passivating agent; this modification eliminates the need to include an additional antifouling diluent, which simplifies the sensor design and fabrication protocol. Copyright © 2015 Elsevier B.V. All rights reserved.

Estimated net acid excretion inversely correlates with urine pH in vegans, lacto-ovo vegetarians, and omnivores.

PubMed

Ausman, Lynne M; Oliver, Lauren M; Goldin, Barry R; Woods, Margo N; Gorbach, Sherwood L; Dwyer, Johanna T

2008-09-01

Diet affects urine pH and acid-base balance. Both excess acid/alkaline ash (EAA) and estimated net acid excretion (NAE) calculations have been used to estimate the effects of diet on urine pH. This study's goal was to determine if free-living vegans, lacto-ovo vegetarians, and omnivores have increasingly acidic urine, and to assess the ability of EAA and estimated NAE calculations to predict urine pH. This study used a cross-sectional design. This study assessed urine samples of 10 vegan, 16 lacto-ovo vegetarian, and 16 healthy omnivorous women in the Boston metropolitan area. Six 3-day food records from each dietary group were analyzed for EAA content and estimated NAE, and correlations with measured urine pH were calculated. The mean (+/- SD) urine pH was 6.15 +/- 0.40 for vegans, 5.90 +/- 0.36 for lacto-ovo vegetarians, and 5.74 +/- 0.21 for omnivores (analysis of variance, P = .013). Calculated EAA values were not significantly different among the three groups, whereas mean estimated NAE values were significantly different: 17.3 +/- 14.5 mEq/day for vegans, 31.3 +/- 8.5 mEq/day for lacto-ovo vegetarians, and 42.6 +/- 13.2 mEq/day for omnivores (analysis of variance, P = .01). The average deattenuated correlation between urine pH and EAA was 0.333; this value was -0.768 for estimated NAE and urine pH, with a regression equation of pH = 6.33 - 0.014 NAE (P = .02, r = -0.54). Habitual diet and estimated NAE calculations indicate the probable ranking of urine pH by dietary groups, and may be used to determine the likely acid-base status of an individual; EAA calculations were not predictive of urine pH.

Human Muscle Protein Synthetic Responses during Weight-Bearing and Non-Weight-Bearing Exercise: A Comparative Study of Exercise Modes and Recovery Nutrition.

PubMed

Pasiakos, Stefan M; McClung, Holly L; Margolis, Lee M; Murphy, Nancy E; Lin, Gregory G; Hydren, Jay R; Young, Andrew J

2015-01-01

Effects of conventional endurance (CE) exercise and essential amino acid (EAA) supplementation on protein turnover are well described. Protein turnover responses to weighted endurance exercise (i.e., load carriage, LC) and EAA may differ from CE, because the mechanical forces and contractile properties of LC and CE likely differ. This study examined muscle protein synthesis (MPS) and whole-body protein turnover in response to LC and CE, with and without EAA supplementation, using stable isotope amino acid tracer infusions. Forty adults (mean ± SD, 22 ± 4 y, 80 ± 10 kg, VO 2peak 4.0 ± 0.5 L ∙ min(-1)) were randomly assigned to perform 90 min, absolute intensity-matched (2.2 ± 0.1 VO2 L ∙ m(-1)) LC (performed on a treadmill wearing a vest equal to 30% of individual body mass, mean ± SD load carried 24 ± 3 kg) or CE (cycle ergometry performed at the same absolute VO2 as LC) exercise, during which EAA (10 g EAA, 3.6 g leucine) or control (CON, non-nutritive) drinks were consumed. Mixed-muscle and myofibrillar MPS were higher during exercise for LC than CE (mode main effect, P < 0.05), independent of dietary treatment. EAA enhanced mixed-muscle and sarcoplasmic MPS during exercise, regardless of mode (drink main effect, P < 0.05). Mixed-muscle and sarcoplasmic MPS were higher in recovery for LC than CE (mode main effect, P < 0.05). No other differences or interactions (mode x drink) were observed. However, EAA attenuated whole-body protein breakdown, increased amino acid oxidation, and enhanced net protein balance in recovery compared to CON, regardless of exercise mode (P < 0.05). These data show that, although whole-body protein turnover responses to absolute VO2-matched LC and CE are the same, LC elicited a greater muscle protein synthetic response than CE.

Expression of growth-related genes in young and older human skeletal muscle following an acute stimulation of protein synthesis.

PubMed

Drummond, Micah J; Miyazaki, Mitsunori; Dreyer, Hans C; Pennings, Bart; Dhanani, Shaheen; Volpi, Elena; Esser, Karyn A; Rasmussen, Blake B

2009-04-01

Muscle growth is associated with an activation of the mTOR signaling pathway and satellite cell regulators. The purpose of this study was to determine whether 17 selected genes associated with mTOR/muscle protein synthesis and the satellite cells/myogenic program are differentially expressed in young and older human skeletal muscle at rest and in response to a potent anabolic stimulus [resistance exercise + essential amino acid ingestion (RE+EAA)]. Twelve male subjects (6 young, 6 old) completed a bout of heavy resistance exercise. Muscle biopsies were obtained before and at 3 and 6 h post RE+EAA. Subjects ingested leucine-enriched essential amino acids at 1 h postexercise. mRNA expression was determined using qRT-PCR. At rest, hVps34 mRNA was elevated in the older subjects (P < 0.05) while there was a tendency for levels of myoD, myogenin, and TSC2 mRNA to be higher than young. The anabolic stimulus (RE+EAA) altered mRNAs associated with mTOR regulation. Notably, REDD2 decreased in both age groups (P < 0.05) but the expression of Rheb mRNA increased only in the young. Finally, cMyc mRNA was elevated (P < 0.05) in both young and old at 6 h post RE+EAA. Furthermore, RE+EAA also increased expression of several mRNAs associated with satellite function in the young (P < 0.05), while expression of these mRNAs did not change in the old. We conclude that several anabolic genes in muscle are more responsive in young men post RE+EAA. Our data provide new insights into the regulation of genes important for transcription and translation in young and old human skeletal muscle post RE+EAA.

Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content.

PubMed

Katsanos, Christos S; Chinkes, David L; Paddon-Jones, Douglas; Zhang, Xiao-jun; Aarsland, Asle; Wolfe, Robert R

2008-10-01

It is recognized that both whey protein (WY) and essential amino acids (EAA) are stimuli for muscle protein anabolism. The aim of the present study was to determine if the effects of WY ingestion on muscle protein accrual in elderly persons are due solely to its constituent EAA content. Fifteen elderly persons were randomly assigned to ingest a bolus of either 15 g of WY, 6.72 g of EAA, or 7.57 g of nonessential amino acids (NEAA). We used the leg arteriovenous model to measure the leg phenylalanine balance, which is an index of muscle protein accrual. Phenylalanine balance (nmol x min(-1) kg lean leg mass(-1)) during the 3.5 hours after the bolus ingestion improved in the WY (-216 +/- 14 vs -105 +/- 19; P < .05) but not in the EAA (-203 +/- 21 vs -172 +/- 38; P > .05) or NEAA groups (-203 +/- 19 vs -204 +/- 21; P > .05). The insulin response (uIU x mL(-1) 210 min(-1)) during the same period was lower in both the NEAA (48 +/- 40) and EAA (213 +/- 127) when compared to the WY (1073 +/- 229; P < .05). In conclusion, WY ingestion improves skeletal muscle protein accrual through mechanisms that are beyond those attributed to its EAA content. This finding may have practical implications for the formulation of nutritional supplements to enhance muscle anabolism in older individuals.

Effects of equine assisted activities on autism spectrum disorder.

PubMed

Lanning, Beth A; Baier, Margaret E Matyastik; Ivey-Hatz, Julie; Krenek, Nancy; Tubbs, Jack D

2014-08-01

Quality of life assessments were used in this study to determine the behavioral changes of children diagnosed with autism spectrum disorder (ASD) who participated in equine assisted activities. Behavioral changes of children with ASD participating in 9 weeks of equines assisted activities (EAA) (N = 10) were compared to behavioral changes of children who participated in a non-equine intervention (N = 8). Parents noted significant improvements in their child's physical, emotional and social functioning following the first 6 weeks of EAA. The children participating in the non-equine program also demonstrated improvement in behavior, but to a lesser degree. The favorable outcome of this study lends support for continuation of programs utilizing EAA in the treatment of children with ASD.

Investigation of amino acid δ 13C signatures in bone collagen to reconstruct human palaeodiets using liquid chromatography-isotope ratio mass spectrometry

NASA Astrophysics Data System (ADS)

Choy, Kyungcheol; Smith, Colin I.; Fuller, Benjamin T.; Richards, Michael P.

2010-11-01

This research presents the individual amino acid δ 13C values in bone collagen of humans ( n = 9) and animals ( n = 27) from two prehistoric shell midden sites in Korea. We obtained complete baseline separation of 16 of the 18 amino acids found in bone collagen by using liquid chromatography-isotope ratio mass spectrometry (LC-IRMS). The isotopic results reveal that the humans and animals in the two sites had similar patterns in essential amino acids (EAAs) and non-essential amino acids (NEAAs). The EAA and NEAA δ 13C values in humans are intermediate between those in marine and terrestrial animals. However, the threonine δ 13C values in humans and animals measured in this study are more highly enriched than those of other amino acids. At both sites, all amino acids in marine animals are 13C-enriched relative to those of the terrestrial animals. The isotopic evidence suggests that the Tongsamdong human had EAAs and NEAAs from marine food resources, while the Nukdo humans mainly had EAAs from terrestrial food resources but obtained NEAAs from both terrestrial and marine resources. The δ 13C isotopic differences in amino acids between marine and terrestrial animals were the largest for glycine (NEAA) and histidine (EAA) and the smallest for tyrosine (NEAA) and phenylalanine (EAA). In addition, threonine among the EAAs also had a large difference (˜8‰) in δ 13C values between marine and terrestrial animals, and has the potential to be used as an isotopic marker in palaeodietary studies. Threonine δ 13C values were used in conjunction with the established Δ 13C Glycine-phenylalanine values and produced three distinct dietary groups (terrestrial, omnivorous, and marine). In addition, threonine δ 13C values and Δ 13C Serine-phenylalanine values were discovered to separate between two dietary groups (terrestrial vs. marine), and these δ 13C values may provide a potential new indicator for investigating the distinction between marine and terrestrial protein sources in human diets.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Partially Intact Protein-Based Diets.

PubMed

Worsøe, Päivi S; Sangild, Per T; van Goudoever, Johannes B; Koletzko, Berthold; van der Beek, Eline M; Abrahamse-Berkeveld, Marieke; Burrin, Douglas G; van de Heijning, Bert J M; Thymann, Thomas

2018-06-13

Current recommendations for protein levels in infant formula are intended to ensure that growth matches or exceeds growth of breastfed infants, but may provide a surplus of amino acids (AAs). Recent infant studies with AA-based formulas support specific adjustment of the essential amino acid (EAA) composition allowing for potential lowering of total protein levels. With the use of a combination of intact protein and free EAAs, we designed a formula that meets these adjusted EAA requirements for infants. Our objective was to test whether this adjusted formula is safe and supports growth in a protein-restricted piglet model, and whether it shows better growth than an isonitrogenous formula based on free AAs. Term piglets (Landrace × Yorkshire × Duroc, n = 72) were fed 1 of 4 isoenergetic formulas containing 70% intact protein and 30% of an EAA mixture or a complete AA-based control for 20 d: standard formula (ST-100), ST-100 with 25% reduction in proteinaceous nitrogen (ST-75), ST-75 with an adjusted EAA composition (O-75), or a diet as O-75, given as a complete AA-based diet (O-75AA). After an initial adaptation period, ST-75 and O-75 pigs showed similar growth rates, both lower than ST-100 pigs (∼25 compared with 31 g · kg-1 · d-1, respectively). The O-75AA pigs showed further reduced growth rate (15 g · kg-1 · d-1) and fat proportion (both P < 0.05, relative to O-75). Formula based partly on intact protein is superior to AA-based formula in this experimental setting. The 25% lower, but EAA-adjusted, partially intact protein-based formula resulted in similar weight gain with a concomitant increased AA catabolism, compared with the standard 25% lower standard formula in artificially reared, protein-restricted piglets. Further studies should investigate if and how the specific EAA adjustments that allow for lowering of total protein levels will affect growth and body composition development in formula-fed infants.

[Comparative analysis of the semiotics of disseminated pulmonary tuberculosis and exogenous allergic alveolitis in accordance with the data of computed tomography].

PubMed

Amansakhedov, R B; Limarova, I V; Perfiliev, A V; Abdullaev, R Yu; Sigaev, A T; Ergeshov, A E

2016-01-01

to improve the differential diagnosis of disseminated pulmonary tuberculosis (DPT) and exogenous allergic alveolitis (EAA) via comparative investigation of their computed tomography (CT) semiotics and identification of the most informative diagnostic criteria. 70 patients, including 40 patients with DPT in a phase of infiltration and 30 patients with acute EAA, were studied using a Somatom Emotion 16 multi-slice spiral CT scanner (Siemens). All the patients underwent spiral scanning from the upper chest aperture to the costodiaphragmatic recesses with a high CT algorithm at 0.8-mm slice thickness and a 1.5-mm step. Analysis of the spread of dissemination foci established that pathological changes were peribronchovascularly located in both nosological entities and characterized by a preponderance of septal and intrabronchial locations in DPT and by a centrilobular distribution in EAA. Centrilobular foci were more commonly poorly defined in EAA and mixed foci were observed in DPT. In the latter, peribronchovascular, centrilobular foci were revealed at a distance from the visceral pleura (the boundary of the deep and superficial lymphatic network, respectively) in 38% and more than half of the cases (62%) with the involvement of the visceral and parietal pleura; in EAA, the centrilobular foci were more often combined with the involvement of the visceral pleura in more than 92% of cases. The tree-in-bud sign was significantly more common in DPT. The latter was mostly characterized by apicocaudal regression of dissemination. In EAA, the foci were more frequently located asymmetrically. Monomorphic foci with destruction, as well as their polymorphism were seen in DPT; those without destruction were predominantly observed in EAA. CT ground glass and mosaic perfusion syndromes were significantly more often in EAA. In DPT, the visceral and parietal pleuras were involved in the process in 62% of cases and changes were also more common in the extrapleural fat. In addition to the peribronchovascular location of foci, the characteristic CT signs for DPT are a preponderance of intrabronchial and septal locations of foci, their apicocaudal regression, the presence of the CT tree-in-bud sign, and thickened extrapleural fat. EAA showed a prevalence of asymmetrical foci with centrilobular location with the involvement of the visceral pleura into the process, with the presence of CT ground glass and mosaic perfusion syndromes, as well as the bronchial lumen visualized in the peripheral segments of the lung.

Occipital and external acoustic meatus to axis angle as a predictor of the oropharyngeal space in healthy volunteers: a novel parameter for craniocervical junction alignment.

PubMed

Morizane, Kazuaki; Takemoto, Mitsuru; Neo, Masashi; Fujibayashi, Shunsuke; Otsuki, Bungo; Kawata, Tomotoshi; Matsuda, Shuichi

2018-05-01

The occipito-C2 angle (O-C2a) influences the oropharyngeal space. However, O-C2a has several limitations. There is no normal value of O-C2a because of the wide individual variations, and O-C2a does not reflect translation of the cranium to the axis, another factor influencing the oropharyngeal space in patients with atlantoaxial subluxation. The objective of this study was to propose a novel parameter that accounts for craniocervical junction alignment (CJA) and the oropharyngeal space. This is a post hoc analysis of craniocervical radiological parameters from another study. Forty healthy volunteers were included in the study. Craniocervical measurement parameters included the occipital and external acoustic meatus to axis angle (O-EAa), the C2 tilting angle (C2Ta), O-C2a, and the anterior-posterior distance of the narrowest oropharyngeal airway space (nPAS). We collected 40 healthy volunteers' lateral cervical radiographs in neutral, flexion, extension, protrusion, and retraction positions. We measured O-C2a, C2Ta (formed by the inferior end plate of C2 and a line connecting the external acoustic meatus and the midpoint of the inferior end plate of C2 [EA-line]), O-EAa (formed by the McGregor line and the EA-line), and nPAS. We evaluated the inter-rater and intrarater reliability of O-EAa and C2Ta, and the associations between each of the measured parameters. The inter-rater and intrarater reliabilities of measuring O-EAa and C2Ta were excellent. The neutral position O-EAa values remained in a narrower range (mean±standard deviation, 90.0°±5.0°) than O-C2a (15.6°±6.7°) (Levene test of equality of variances, p=.044). In the linear mixed-effects models, sex, O-C2a, C2Ta, and O-EAa were significantly associated with nPAS. The marginal R 2 values for the mixed-effect models, which express the variance explained by fixed effects, were 0.605 and 0.632 for the O-C2a and O-EAa models, respectively. In all models, the subaxial alignment (C2-C6a) had no significant association with nPAS. The O-EAa may be a useful parameter of CJA with several advantages over O-C2a, including less individual variation, easier visual recognition during surgery, and improved prediction of postoperative nPAS after occipitocervical fusion. Copyright © 2017 Elsevier Inc. All rights reserved.

Environmentally Compliant Thermoplastic Powder Coating, Phase 1

DTIC Science & Technology

1992-10-07

TPC flame sprayed application equipment and ethylene acrylic acid (EAA) and ethylene methacrylic acid (EMAA) copolymers thermoplastic powder...have worked closely with Dow Chemical to develop and optimize their systems using Dow "Envelon" ethylene acrylic acid (EAA) thermoplastic copolymers...provide on/off control. CFS recommends the use of Dow "Envelon" ethylene acrylic acid (EAA) copolymer thermoplastic powder with this unit. The CFS system

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men

PubMed Central

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-01-01

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12–15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally. PMID:29671767

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men.

PubMed

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-04-19

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.

Antimicrobial activity of flavanoid sulphates and other fractions of Argyreia speciosa (Burm.f) Boj.

PubMed

Habbu, P V; Mahadevan, K M; Shastry, R A; Manjunatha, H

2009-02-01

Antimicrobial activity of flavanoid sulphates and different fractions of A. speciosa root was studied against bacteria, fungi and Mycobacterium tuberculosis H37 Rv sensitive strain by in vitro and in vivo assays. Flavanoid sulphates such as quercetin 3'7 di-O methyl 3- sulphate and kaempferol 7-O methyl 3-sulphate were isolated from the n-butanol fraction of 80% methanolic extract of the plant. The structures of the isolated flavanoids were confirmed by spectral studies. Ethyl acetate (EAAS) fraction and flavanoid sulphates inhibited the growth of M. tuberculosis Rv sensitive strain at MIC values 50 and 25 microg/ml, respectively. Ethanolic fraction (EtAS) showed significant inhibition of gram positive organism with a MIC of 31.25 microg/ml. More inhibition was observed with a less MIC (2 microg/ml) for flavanoid sulphates against Klebsiella pneumoniae, a gram negative organism and it is almost comparable with the standards. Interestingly, chloroform fraction alone exhibited significant antifungal activity with a MIC of 100 microg/ml. A synergistic effect between flavanoids sulphates and commercially available antitubercular drugs was observed with FIC index of 0.443 +/- 0.245, 0.487 +/- 0.247 for isoniazid and 0.468 +/- 0.333, 0.417 +/- 0.345 for rifampicin, whereas EAAS fraction showed partial synergistic effect. A synergistic effect was observed for EAAS fraction and flavanoids sulphates with FIC index < 0.5 with antibiotics. Hemolysis assay on RBCs suggested that EAAS and flavanoids sulphates exhibited least cellular toxicity to erythrocytes as compared to chloramphenicol. In vivo studies in mice infected with K. pneumoniae demonstrated that on day 10 post treatment of different fractions and isolated compounds of A. speciosa, about 60% of the animals treated with EAAS, 70% of animals treated with flavanoids sulphates and 40% of animals treated with EtAS were survived.

Unaffected Arm Muscle Hypercatabolism in Dysphagic Subacute Stroke Patients: The Effects of Essential Amino Acid Supplementation

PubMed Central

Aquilani, Roberto; Boselli, Mirella; D'Antona, Giuseppe; Baiardi, Paola; Boschi, Federica; Viglio, Simona; Iadarola, Paolo; Pasini, Evasio; Barbieri, Annalisa; Dossena, Maurizia; Bongiorno, Andria Innocenza; Verri, Manuela

2014-01-01

Alterations in muscle protein turnover of the unaffected side of stroke patients could contribute to physical disability. We investigated whether hypercatabolic activity occurred in unaffected arm muscle and whether supplemented essential amino acids (EAAs) could limit muscle hypercatabolism (MH). Thirty-eight dysphagic subacute stroke subjects (<3 months after acute event) (29 males + 9 females; 69.7 ± 11.4 yrs) were enrolled and randomized to receive 8 g/day EAAs (n = 19; EAA group) or isocaloric placebo (maltodextrin; n = 19, Plac group). Before randomization, all patients had their arterial (A) and venous (V) amino acids measured and muscle (A − V) differences calculated in the unaffected arm. Eight matched and healthy subjects served as controls. When compared to healthy controls, the entire stroke population showed significant muscle release (= negative value A − V) of the amino acid phenylalanine (phenyl-) indicating a prevalence of MH. Moreover, randomized EAA and Plac groups had similar rates of MH. After 38 days from the start of the protocol, the EAA group but not the Plac group had MH converted to balanced protein turnover or anabolic activity. We concluded that muscle protein metabolism of the unaffected arm of dysphagic subacute stroke individuals could be characterized by MH which can be corrected by supplemented EAAs. PMID:25431770

Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women.

PubMed

O'Donnell, Emma; Goodman, Jack M; Harvey, Paula J

2011-12-01

Evidence indicates that hypoestrogenemia is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovulatory disruption due to functional hypothalamic amenorrhea (FHA) are characterized by hypoestrogenemia. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Articles were found via PubMed search for both original and review articles based on peer review publications between 1974 and 2011 reporting on cardiovascular changes in women with FHA, with emphasis placed on women with EAA. Despite participation in regular exercise training, hypoestrogenic women with EAA demonstrate paradoxical changes in cardiovascular function, including endothelial dysfunction, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest that the beneficial effects of regular exercise training on vascular function are obviated in the face of hypoestrogenemia. The long-term cardiovascular consequences of altered vascular function in response to ovulatory disruption in women with EAA remain to be determined. Retrospective data, however, suggest premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovulatory disruption. Importantly, in women with EAA, estrogen therapy, folic acid supplementation without change in menstrual status, and resumption of menses restores endothelial function. In this review, we focus on the influence of hypoestrogenemia in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, lipid profile, and autonomic control of blood pressure, heart rate, and baroreflex sensitivity. The influence of exercise training is also considered. With the premenopausal years typically considered to be cardioprotective in association with normal ovarian function, ovarian disruption in women with EAA is of importance. Further investigation of the short-term, and potentially long-term, cardiovascular consequences of hypoestrogenemia in women with EAA is recommended.

Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise.

PubMed

Moberg, Marcus; Apró, William; Ekblom, Björn; van Hall, Gerrit; Holmberg, Hans-Christer; Blomstrand, Eva

2016-06-01

Protein synthesis is stimulated by resistance exercise and intake of amino acids, in particular leucine. Moreover, activation of mammalian target of rapamycin complex 1 (mTORC1) signaling by leucine is potentiated by the presence of other essential amino acids (EAA). However, the contribution of the branched-chain amino acids (BCAA) to this effect is yet unknown. Here we compare the stimulatory role of leucine, BCAA, and EAA ingestion on anabolic signaling following exercise. Accordingly, eight trained volunteers completed four sessions of resistance exercise during which they ingested either placebo, leucine, BCAA, or EAA (including the BCAA) in random order. Muscle biopsies were taken at rest, immediately after exercise, and following 90 and 180 min of recovery. Following 90 min of recovery the activity of S6 kinase 1 (S6K1) was greater than at rest in all four trials (Placebo

Implementing a national early awareness and alert system for new and emerging health technologies in Italy: the COTE Project.

PubMed

Migliore, Antonio; Perrini, Maria Rosaria; Jefferson, Tom; Cerbo, Marina

2012-07-01

The aim of this study was to establish a national Early Awareness and Alert (EAA) system for the identification and assessment of new and emerging health technologies in Italy. In 2008, Agenas, a public body supporting Regions and the Ministry of Health (MoH) in health services research, started a project named COTE (Observatory of New and Emerging Health Technologies) with the ultimate aim of implementing a national EAA system. The COTE project involved all stakeholders (MoH, Regions, Industry, Universities, technical government bodies, and Scientific Societies), in defining the key characteristics and methods of the EAA system. Agreement with stakeholders was reached using three separate workshops. During the workshops, participants shared and agreed methods for identification of new and emerging health technologies, prioritization, and assessment. The structure of the Horizon Scanning (HS) reports was discussed and defined. The main channels for dissemination of outputs were identified as the EuroScan database, and the stakeholders' Web portals. During the final workshop, Agenas presented the first three HS reports produced at national level and proposed the establishment of a permanent national EAA system. The COTE Project created the basis for a permanent national EAA system in Italy. An infrastructure to enable the stakeholders network to grow was created, methods to submit new and emerging health technologies for possible evaluation were established, methods for assessment of the technologies selected were defined, and the stakeholders involvement was delineated (in the identification, assessment, and dissemination stages).

AV3V lesions attenuate the cardiovascular responses produced by blood-borne excitatory amino acid analogs

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Beltz, T. G.; Lewis, S. J.; Johnson, A. K.

1999-01-01

Systemic injections of the excitatory amino acid (EAA) analogs, kainic acid (KA) and N-methyl-D-aspartate (NMDA), produce a pressor response in conscious rats that is caused by a centrally mediated activation of sympathetic drive and the release of arginine vasopressin (AVP). This study tested the hypothesis that the tissue surrounding the anteroventral part of the third ventricle (AV3V) plays a role in the expression of the pressor responses produced by systemically injected EAA analogs. Specifically, we examined whether prior electrolytic ablation of the AV3V region would affect the pressor responses to KA and NMDA (1 mg/kg iv) in conscious rats. The KA-induced pressor response was smaller in AV3V-lesioned than in sham-lesioned rats (11 +/- 2 vs. 29 +/- 2 mmHg; P < 0.05). After ganglion blockade, KA produced a pressor response in sham-lesioned but not AV3V-lesioned rats (+27 +/- 3 vs. +1 +/- 2 mmHg; P < 0.05). The KA-induced pressor response in ganglion-blocked sham-lesioned rats was abolished by a vasopressin V1-receptor antagonist. Similar results were obtained with NMDA. The pressor response to AVP (10 ng/kg iv) was slightly smaller in AV3V-lesioned than in sham-lesioned ganglion-blocked rats (45 +/- 3 vs. 57 +/- 4 mmHg; P < 0.05). This study demonstrates that the pressor responses to systemically injected EAA analogs are smaller in AV3V-lesioned rats. The EAA analogs may produce pressor responses by stimulation of EAA receptors in the AV3V region, or the AV3V region may play an important role in the expression of these responses.

[Study of biological value of beef produced by interspecies hybrids of domestic cattle and wild yaks].

PubMed

Bagirov, V A; Chernukha, I M; Lisitsin, A V; Zinovieva, N A

2014-01-01

The comparative study of the chemical composition and biological values of beef produced by hybrids of Angus cattle with wild yaks (hybrid beef) and pure-bred Angus cattle (traditional beef) has been carried out. Longissimus muscle samples were used for analysis. It was observed, that the hybrid beef samples had the practically equal protein content comparing to traditional beef (21.1 vs. 21.6 per cent) but were characterized by the lower fat content (1.2 vs. 2.5 per cent). The higher biological value of hybrid beef comparing to traditional beef has been shown. The value of protein-quality index, calculated as the ratio of tryptophan amino acid to oxyprolin and characterizing the ratio of high biological value proteins to low biological value proteins was 8.1 vs. 5.7. The values of amino acid indexes [ratio of essential amino acids (EAA) to non-essential amino acids (NAA) and ratio of EAA to the total amount of amino acids (TAA)] were EAA/NAA = 0.77 vs. 0.65 and EAA/TAA = 0.43 vs. 0.39. The protein of hybrid beef was characterized by the higher content of a number of the essential amino acids: by a factor of 1, 77 for threonin, 1.23--for valin, 1.09--for lysin, 1.17--for leucine and 1.19--for tryptophan. The amount of the essential amino acids in 1 gram of protein of the hybrid beef was 434.7 mg against 393.1 mg for traditional beef It has been shown, that the protein of the hybrid beef comparing to traditional beef is characterized by the higher values of the amino acid scores calculated for EAA.

Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation.

PubMed

David, Cristiana; Peride, Ileana; Niculae, Andrei; Constantin, Alexandra Maria; Checherita, Ionel Alexandru

2016-09-20

Native arteriovenous fistula (AVF) is the most appropriate type of vascular access for chronic dialysis. Its patency rates depend on vascular wall characteristics. Ketoacid analogues of essential amino acids (KA/EAA) are prescribed in end-stage renal disease (ESRD) pre-dialysis patients to lower toxic metabolic products generation and improve nutritional status. We hypothesized that very-low protein diet (VLPD) supplemented with KA/EAA may influence arterial wall stiffness and affect AVF maturation rates and duration in pre-dialysis ESRD patients. In a prospective, cohort, 3 years study we enrolled 67 consecutive non-diabetic early referral ESRD patients that underwent AVF creation in our hospital. Patients were divided in two groups based on their regimen 12 months prior to surgery: a VLPD supplemented with KA/EAA study group versus a low protein diet non-KA/EAA-supplemented control group. For each patient we performed serum analysis for the parameters of bone mineral disease, inflammation and nutritional status, one pulse wave velocity (PWV) measurement and one Doppler ultrasound (US) determination prior the surgery, followed by consequent Doppler US assessments at 4, 6, 8 and 12 weeks after it. Rates and duration of mature AVF achievement were noted. We used logistic regression to analyze the association between AVF maturation and KA/EAA administration, by comparing rates and durations between groups, unadjusted and adjusted for systolic blood pressure, C-reactive protein, PWV, phosphorus values. All parameters in the logistic model were transformed in binary variables. A p-value < α = 0.05 was considered significant; data were processed using SPSS 16 software and Excel. In the study group (n = 28, aged 57 ± 12.35, 13 females) we registered better serum phosphate (p = 0.022) and C-reactive protein control (p = 0.021), lower PWV (p = 0.007) and a higher percent of AVF creation success (33.3 % versus 17.8 %, p < 0.05). AVF maturation duration was lower in study group (5.91 versus 7.15 weeks, p < 0.001). VLPD supplemented with KA/EAA appear to improve the native AVF primary outcome, decreasing the initial vascular stiffness, possible by preserving vascular wall quality in CKD patients through a better serum phosphate levels control and the limitation of inflammatory response.

Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows.

PubMed

Larsen, M; Kristensen, N B

2009-07-01

Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM. Cows were sampled prepartum and at 4, 15, and 29 DIM. Postpartum dry matter intake increased at a lower rate with infusion compared with the control. Arterial concentrations of all essential AA (EAA) were lower with infusion compared with the control. Net portal fluxes of His, Ile, Leu, Lys, Met, Phe, Thr, Val, Ala, Pro, Ser, and Tyr were lower with infusion compared with the control and the net portal fluxes of these AA showed positive correlations with dry matter intake, whereas the net portal fluxes of Asp, Glu, and Gln were unaffected by treatment. Net hepatic fluxes of EAA were not affected by treatment but increased as lactation progressed with both treatments. On a net basis, all EAA were removed by the liver prepartum and at 4 DIM, whereas Met, Phe, and Thr were the only EAA being removed at 29 DIM. Except for Ala, AA removed by the liver might be used primarily for noncatabolic processes, as exemplified by the 16% of hepatic Gly uptake accounted for as urinary hippurate. The measured hepatic uptake of glucogenic precursors (glucogenic AA, volatile fatty acids, lactate, and glycerol) accounted for 50 to 90% of the hepatic release of glucose. The hepatic urea output accounted for more than 100% of the hepatic ureagenic precursor uptake, indicating that the glucogenic precursors unaccounted for are nonnitrogen-containing compounds. In conclusion, an increased exogenous glucose supply to the small intestine did not seem to affect the amount of EAA and non-EAA available for peripheral tissues in early lactation, and the study did not indicate an AA-sparing effect of small intestinal glucose absorption. In periparturient dairy cows, hepatic catabolism of AA was not driven by the increased whole-body demand for glucose, and Ala was the only AA that contributed substantially to hepatic gluconeogenesis. In very early lactation, the supply of EAA might be of greater concern than the supply of glucogenic substrates.

Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum.

PubMed

Ruocco, L A; Treno, C; Gironi Carnevale, U A; Arra, C; Mattern, C; Huston, J P; de Souza Silva, M A; Nikolaus, S; Scorziello, A; Nieddu, M; Boatto, G; Illiano, P; Pagano, C; Tino, A; Sadile, A G

2014-09-01

Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EAA) function in prepuberal rats of the Naples high-excitability (NHE) line, an animal model for attention-deficit hyperactivity disorder (ADHD) and normal random bred (NRB) controls. NHE and NRB rats were daily administered IN-DA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal days 28-42 and subsequently tested in the Làt maze and in the Eight-arm radial Olton maze. Soluble and membrane-trapped L-glutamate (L-Glu) and L-aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined after sacrifice in IN-DA- and vehicle-treated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover, DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area (VTA) and substantia nigra, respectively. In NHE rats, IN-DA (0.30 mg/kg) decreased horizontal activity and increased nonselective attention relative to vehicle, whereas the lower dose (0.15 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EAAs were reduced in PFc and DS relative to NRB controls, while membrane-trapped EAAs were elevated in VS. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. In addition, DAT protein levels were elevated in PFc and VS relative to NRB controls. IN-DA led to a number of changes of EAA, NMDAR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between lines. Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction in striatal DA hyperactivity and, possibly, DA action on striatal EAA levels, resulting in a decrease of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central DAergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal  DA by indicating an enhancement of selective attention and working memory in a deficit model.

Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

NASA Technical Reports Server (NTRS)

Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Creson, Daniel L.; Sanford, Arthur P.; Wolf, Steven E.; Wolfe, Robert R.; Ferrando, Arny A.

2003-01-01

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

Commensal bacteria and essential amino acids control food choice behavior and reproduction

PubMed Central

Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M.; Piper, Matthew D. W.

2017-01-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits. PMID:28441450

Commensal bacteria and essential amino acids control food choice behavior and reproduction.

PubMed

Leitão-Gonçalves, Ricardo; Carvalho-Santos, Zita; Francisco, Ana Patrícia; Fioreze, Gabriela Tondolo; Anjos, Margarida; Baltazar, Célia; Elias, Ana Paula; Itskov, Pavel M; Piper, Matthew D W; Ribeiro, Carlos

2017-04-01

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.

Proximate composition and nutritional quality of deep sea growth sea cucumbers (Stichopus japonicus) from different origins.

PubMed

Gao, Yue; Li, Zhibo; Qi, Yanxia; Guo, Zhenyu; Lin, Yantong; Li, Wei; Hu, Yucai; Zhao, Qiancheng

2016-05-01

Deep sea growth sea cucumber (Stichopus japonicus) (DSG-SC) is considered a most nutritious and luxurious seafood in Asia. This study compared the proximate composition and nutritional quality of collagen, polysaccharides, amino acids (AAs) and fatty acids (FAs) in DSG-SCs from different origins. The contents of protein, ash, carbohydrate, fat, collagen, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), total amino acids (TAAs), essential amino acids (EAAs), fucose and uronic acid differed among the origins. DSG-SC of Dalian origin had lower contents of ash, fat, uronic acid, TAAs and EAAs but higher contents of protein, collagen, PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and fucose compared with the other origins. DSG-SCs had a higher proportion of PUFAs and were richer in polysaccharides than other seafood. Glutamate and glycine were the dominant AAs, while leucine and threonine were the most abundant EAAs. DSG-SCs are a good source of collagen, polysaccharides (especially fucose), EAAs (especially leucine and threonine) and PUFAs (especially EPA and DHA). Dalian seems to be a promising origin to produce high-value sea cucumber with high PUFA, fucose, collagen and protein contents. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Extrinsic allergic alveolitis as an uncommon diagnostic pitfall in lung cytology.

PubMed

Midi, Ahmet; Yener, Neşe Arzu; Orki, Alpay; Cubuk, Rahmi; Ersev, Ayse

2012-08-01

House paints, the industrial products of toxic chemicals are known to be linked with severe respiratory disturbances especially in inadequately ventilated places. In this study, we aimed to report a biopsy-proven case of extrinsic allergic alveolitis (EAA) who presented with nonspecific respiratory symptoms 1 month after having her whole house interior painted. At CT scanning, we observed the ground glass opacities and the micronodular pattern typical for EAA and also a solid, consolidative lung area, highly suggestive of malignancy. The case initially was misinterpreted as a malignant tumor both radiologically and cytologically at CT-guided transthoracic fine needle aspiration biopsy. The final pathologic diagnosis was given as EAA on frozen section performed during thoracotomy operation. The patient received short-term steroid treatment and has been doing well for the last 7 months after her operation. As a conclusion, when assessing a cytologic material from a patient who has got a solid lung mass and also a history of chemical dye exposure, consolidative mass formation which is a rare form of EAA should always be kept in mind. Another final point is that the appropriate ventilation should be achieved if the exposure with the house paint chemicals is inevitable. Copyright © 2011 Wiley Periodicals, Inc.

Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids.

PubMed

Dickinson, Jared M; Fry, Christopher S; Drummond, Micah J; Gundermann, David M; Walker, Dillon K; Glynn, Erin L; Timmerman, Kyle L; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

2011-05-01

The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

Early adolescent adversity inflates threat estimation in females and promotes alcohol use initiation in both sexes.

PubMed

Walker, Rachel A; Andreansky, Christopher; Ray, Madelyn H; McDannald, Michael A

2018-06-01

Childhood adversity is associated with exaggerated threat processing and earlier alcohol use initiation. Conclusive links remain elusive, as childhood adversity typically co-occurs with detrimental socioeconomic factors, and its impact is likely moderated by biological sex. To unravel the complex relationships among childhood adversity, sex, threat estimation, and alcohol use initiation, we exposed female and male Long-Evans rats to early adolescent adversity (EAA). In adulthood, >50 days following the last adverse experience, threat estimation was assessed using a novel fear discrimination procedure in which cues predict a unique probability of footshock: danger (p = 1.00), uncertainty (p = .25), and safety (p = .00). Alcohol use initiation was assessed using voluntary access to 20% ethanol, >90 days following the last adverse experience. During development, EAA slowed body weight gain in both females and males. In adulthood, EAA selectively inflated female threat estimation, exaggerating fear to uncertainty and safety, but promoted alcohol use initiation across sexes. Meaningful relationships between threat estimation and alcohol use initiation were not observed, underscoring the independent effects of EAA. Results isolate the contribution of EAA to adult threat estimation, alcohol use initiation, and reveal moderation by biological sex. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effect of probiotics and thyme essential oil on the essential amino acid content of the broiler chicken meat.

PubMed

Alfaig, Ebrahim; Angelovičova, Maria; Kral, Martin; Bučko, Ondrej

2014-01-01

Differences in the types and percentages of essential amino acids (EAAs) in food could influence the value of protein consumed and proteins with a high content of EAAs are the most important components of poultry meat. The use of probiotics for meat and carcass quality improvement has been questioned, while feed supplementation with thyme essential oil (TEO) could be considered as useful natural supplement to be applied in the poultry industry to improve meat quality. Day-old broilers Ross 308 (n = 400) were randomly divided into four groups based on the feed supplement as follows: control, probiotics 0.05%, TEO 0.05% and combination of probiotics and TEO, while the fattening period was 42 days. Six birds of both sexes from each group were selected as a sample, slaughtered and then stored (-18°C) for 6 months till the analysis. The muscular homogeneous sample (50 g) from the breast and thigh of each sample bird was analysed by the Fourier Transform Infrared Spectroscopy method using the device Nicolet 6700. The essential amino acids content was determined and the quality indicators include chemical score, amino acid score, EAA index and biological value were calculated. The obtained results show that for all the tested EAAs of the breast and thigh muscles, the content numerically increased gradually and progressively within the groups as the control scored the minimum followed by the probiotics group, then the combination group and finally the TEO group which scored the highest results. It can be concluded that the TEO promoted the increase of all the EAAs and consequently the quality indicators with significant different compared with the control group and significantly different for some EAAs and quality indicators compared with the probiotics group and the combination group.

Soil Management Effects on Gas Fluxes from an Organic Soil Agricultural System

NASA Astrophysics Data System (ADS)

Jennewein, S. P.; Bhadha, J. H.; Lang, T. A.; Singh, M.; Daroub, S. H.; McCray, M.

2015-12-01

The role of soil management on gas flux isn't well understood for Histosols of the Everglades Agricultural Area (EAA) of southern Florida. The region is responsible for roughly half of sugarcane (Saccharum spp. hybrids) production in the USA along with supplying winter vegetable crops to the eastern USA. Future productivity in the EAA is jeopardized by soil subsidence resulting from oxidation of organic matter. Establishing the role of tillage, water-table depth, nitrogen fertilizer, and soil depth on gas flux will help determine how effective various managements are on conserving soil. Ongoing lysimeter and field studies examined effects of management practices (water-table, tillage, and nitrogen fertilizer), and soil depth on, gas emission and microbial biomass. The trials were set in Belle Glade, FL, on Lauderhill muck (Lithic Haplosaprists). Results to be presented include soil microbial biomass and soil gas (CO2, CH4, and N2O) flux. This study provides insight into management effectiveness and agriculture sustainability on shallow muck soils of the EAA and will help farmers mitigate problems associated with soil subsidence and seasonally high water-tables.

Preparation and luminescent properties of the novel polymer-rare earth complexes composed of Poly(ethylene-co-acrylic acid) and Europium ions

NASA Astrophysics Data System (ADS)

Wu, Yuewen; Hao, Haixia; Wu, Qingyao; Gao, Zihan; Xie, Hongde

2018-06-01

A series of novel polymer-rare earth complexes with Eu3+ ions have been synthesized and investigated successfully, including the binary complexes containing the single ligand poly(ethylene-co-acrylic acid) (EAA) and the ternary complexes using 1,10-phenanthroline (phen), dibenzoylmethane (DBM) or thenoyltrifluoroacetone (TTA) as the second ligand. Their structures have been characterized by Fourier transform infrared spectroscopy (FT-IR), elemental analysis and X-ray diffraction (XRD), which confirm that both EAA and small molecules participate in the coordination reaction with rare earth ions, and they can disperse homogeneously in the polymer matrixes. Both ultraviolet-visible (UV-vis) absorption and photoluminescence tests for the complexes have been recorded. The relationship between fluorescence intensity of polymer-rare earth complexes and the quantity of ligand EAA has been studied and discussed. The films casted from the complexes solution can emit strong characteristic red light under UV light excitation. All these results suggest that the complexes possess potential application as luminescent materials.

15 CFR 742.19 - Anti-terrorism: North Korea.

Code of Federal Regulations, 2010 CFR

2010-01-01

...-users or nuclear end-uses. Applications for non-nuclear end-users or for non-nuclear end-uses, excluding... Korea under section 6(a) of the EAA. License applications for items reviewed under section 6(a) controls... processing license applications for items controlled under EAA section 6(j).) (b) Licensing policy. (1...

15 CFR 742.19 - Anti-terrorism: North Korea.

Code of Federal Regulations, 2011 CFR

2011-01-01

... reexport is destined to nuclear end-users or nuclear end-uses. Applications for non-nuclear end-users or... Korea under section 6(a) of the EAA. License applications for items reviewed under section 6(a) controls... processing license applications for items controlled under EAA section 6(j).) (b) Licensing policy. (1...

15 CFR 764.2 - Violations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... prohibited by or contrary to, or refrain from engaging in any conduct required by, the EAA, the EAR, or any... prohibited, or the omission of any act required, by the EAA, the EAR, or any order, license or authorization..., the EAR, or any order, license or authorization issued thereunder. (d) Conspiracy. No person may...

15 CFR 764.2 - Violations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... prohibited by or contrary to, or refrain from engaging in any conduct required by, the EAA, the EAR, or any... prohibited, or the omission of any act required, by the EAA, the EAR, or any order, license or authorization..., the EAR, or any order, license or authorization issued thereunder. (d) Conspiracy. No person may...

15 CFR 764.2 - Violations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... prohibited by or contrary to, or refrain from engaging in any conduct required by, the EAA, the EAR, or any... prohibited, or the omission of any act required, by the EAA, the EAR, or any order, license or authorization..., the EAR, or any order, license or authorization issued thereunder. (d) Conspiracy. No person may...

15 CFR 764.2 - Violations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... prohibited by or contrary to, or refrain from engaging in any conduct required by, the EAA, the EAR, or any... prohibited, or the omission of any act required, by the EAA, the EAR, or any order, license or authorization..., the EAR, or any order, license or authorization issued thereunder. (d) Conspiracy. No person may...

15 CFR 764.2 - Violations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... prohibited by or contrary to, or refrain from engaging in any conduct required by, the EAA, the EAR, or any... prohibited, or the omission of any act required, by the EAA, the EAR, or any order, license or authorization..., the EAR, or any order, license or authorization issued thereunder. (d) Conspiracy. No person may...

A carnivore embryo's perspective on essential amino acids and ammonium in culture medium: effects on the development of feline embryos.

PubMed

Herrick, Jason R; Lyons, Sarah M; Greene-Ermisch, Alison F; Broeckling, Corey D; Schoolcraft, William B; Krisher, Rebecca L

2018-05-18

Carnivores are an interesting model for studies of embryonic amino acid metabolism and ammonium (NH4+) toxicity given the high protein content of their diets. Our objectives were to examine concentration- and stage-specific effects of essential amino acids (EAA; 0x, 0.125x, 0.25x, 0.5x, or 1.0x the concentrations in Minimum Essential Medium) and NH4+ (0, 300, or 600 μM) on the development and metabolism of feline embryos. The presence of EAA, regardless of concentration, during days 3 to 7 of culture increased (P < 0.01) the proportion of embryos that initiated hatching (>14.3%) and the total number of cells per blastocyst (>148.3 cells) compared to embryos cultured without EAA (0.0% and 113.2 ± 3.7 cells, respectively). The presence of EAA during days 1 to 3 (0.25x) and 3 to 7 (1.0x) of culture increased (P < 0.01) the proportions of embryos that formed blastocysts (82.9 ± 4.2%) and initiated hatching (32.9 ± 5.2%), and the number of cells per blastocyst (247.9 ± 12.1 cells), compared to control embryos (60.0 ± 5.3%, 0.0%, 123.2 ± 8.1 cells, respectively). The presence of NH4+ in the medium did not affect (P > 0.05) development of feline embryos. The addition of EAA or NH4+ during culture did not affect (P > 0.05) the production of Gln by feline embryos, but decreased (P < 0.05) production of Ala and increased (P < 0.05) production of urea. Additional work is needed to determine if our observations are unique to feline embryos or reflect an adaptation to a high protein diet that is conserved in other carnivores.

LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

PubMed

Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

2015-05-22

Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

How Usability Testing Resulted in Improvements to Ground Collision Software for General Aviation: Improved Ground Collision Avoidance System (IGCAS)

NASA Technical Reports Server (NTRS)

Lamarr, Michael; Chinske, Chris; Williams, Ethan; Law, Cameron; Skoog, Mark; Sorokowski, Paul

2016-01-01

The NASA improved Ground Collision Avoidance System (iGCAS) team conducted an onsite usability study at Experimental Aircraft Association (EAA) Air Venture in Oshkosh, Wisconsin from July 19 through July 26, 2015. EAA Air Venture had approximately 550,000 attendees from which the sample pool of pilots were selected. The objectives of this study were to assess the overall appropriateness and acceptability of iGCAS as a warning system for General Aviation aircraft, usability of the iGCAS displays and audio cues, test terrain avoidance characteristics, performance, functionality, pilot response time, and correlate terrain avoidance performance and pilot response time data.

Perceptions of Disability and Special Education among East Asian Parents: U.S. Immigrants and Non-Immigrants

ERIC Educational Resources Information Center

Yan, Min-Chi; Kim, Sunyoung; Kang, Hyun-Ju; Wilkerson, Kimber L.

2017-01-01

The purpose of the current literature review is to understand how East Asian American (EAA) parents of students with disabilities perceive disabilities and special education. These parental perspectives are compared to those of their East Asian (EA) parents to better understand whether EAA parents adjust their perceptions in the U.S. Findings from…

Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis) Caused by Sphingobacterium spiritivorum from the Water Reservoir of a Steam Iron

PubMed Central

Kämpfer, Peter; Engelhart, S.; Rolke, M.; Sennekamp, J.

2005-01-01

A case of extrinsic allergic alveolitis (EAA) caused by Sphingobacterium spiritivorum is described. The symptoms were associated with the use of a steam iron. The water reservoir was heavily contaminated with S. spiritivorum (106 CFU ml−1). This is the first report of S. spiritivorum as a causative agent of EAA. PMID:16145174

Essential amino acids: master regulators of nutrition and environmental footprint?

PubMed Central

Tessari, Paolo; Lante, Anna; Mosca, Giuliano

2016-01-01

The environmental footprint of animal food production is considered several-fold greater than that of crops cultivation. Therefore, the choice between animal and vegetarian diets may have a relevant environmental impact. In such comparisons however, an often neglected issue is the nutritional value of foods. Previous estimates of nutrients’ environmental footprint had predominantly been based on either food raw weight or caloric content, not in respect to human requirements. Essential amino acids (EAAs) are key parameters in food quality assessment. We re-evaluated here the environmental footprint (expressed both as land use for production and as Green House Gas Emission (GHGE), of some animal and vegetal foods, titrated to provide EAAs amounts in respect to human requirements. Production of high-quality animal proteins, in amounts sufficient to match the Recommended Daily Allowances of all the EAAs, would require a land use and a GHGE approximately equal, greater o smaller (by only ±1-fold), than that necessary to produce vegetal proteins, except for soybeans, that exhibited the smallest footprint. This new analysis downsizes the common concept of a large advantage, in respect to environmental footprint, of crops vs. animal foods production, when human requirements of EAAs are used for reference. PMID:27221394

Essential amino acids: master regulators of nutrition and environmental footprint?

PubMed

Tessari, Paolo; Lante, Anna; Mosca, Giuliano

2016-05-25

The environmental footprint of animal food production is considered several-fold greater than that of crops cultivation. Therefore, the choice between animal and vegetarian diets may have a relevant environmental impact. In such comparisons however, an often neglected issue is the nutritional value of foods. Previous estimates of nutrients' environmental footprint had predominantly been based on either food raw weight or caloric content, not in respect to human requirements. Essential amino acids (EAAs) are key parameters in food quality assessment. We re-evaluated here the environmental footprint (expressed both as land use for production and as Green House Gas Emission (GHGE), of some animal and vegetal foods, titrated to provide EAAs amounts in respect to human requirements. Production of high-quality animal proteins, in amounts sufficient to match the Recommended Daily Allowances of all the EAAs, would require a land use and a GHGE approximately equal, greater o smaller (by only ±1-fold), than that necessary to produce vegetal proteins, except for soybeans, that exhibited the smallest footprint. This new analysis downsizes the common concept of a large advantage, in respect to environmental footprint, of crops vs. animal foods production, when human requirements of EAAs are used for reference.

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant

PubMed Central

Robertson, W; Robertson, A S; Burge, C B S G; Moore, V C; Jaakkola, M S; Dawkins, P A; Burd, M; Rawbone, R; Gardner, I; Kinoulty, M; Crook, B; Evans, G S; Harris‐Roberts, J; Rice, S; Burge, P S

2007-01-01

Background Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work‐related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. Methods The outbreak was investigated in a three‐phase cross‐sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. Results 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work‐related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Conclusions Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance. PMID:17504818

Clinical investigation of an outbreak of alveolitis and asthma in a car engine manufacturing plant.

PubMed

Robertson, W; Robertson, A S; Burge, C B S G; Moore, V C; Jaakkola, M S; Dawkins, P A; Burd, M; Rawbone, R; Gardner, I; Kinoulty, M; Crook, B; Evans, G S; Harris-Roberts, J; Rice, S; Burge, P S

2007-11-01

Exposure to metal working fluid (MWF) has been associated with outbreaks of extrinsic allergic alveolitis (EAA) in the USA, with bacterial contamination of MWF being a possible cause, but is uncommon in the UK. Twelve workers developed EAA in a car engine manufacturing plant in the UK, presenting clinically between December 2003 and May 2004. This paper reports the subsequent epidemiological investigation of the whole workforce. The study had three aims: (1) to measure the extent of the outbreak by identifying other workers who may have developed EAA or other work-related respiratory diseases; (2) to provide case detection so that those affected could be treated; and (3) to provide epidemiological data to identify the cause of the outbreak. The outbreak was investigated in a three-phase cross-sectional survey of the workforce. In phase I a respiratory screening questionnaire was completed by 808/836 workers (96.7%) in May 2004. In phase II 481 employees with at least one respiratory symptom on screening and 50 asymptomatic controls were invited for investigation at the factory in June 2004. This included a questionnaire, spirometry and clinical opinion. 454/481 (94.4%) responded and 48/50 (96%) controls. Workers were identified who needed further investigation and serial measurements of peak expiratory flow (PEF). In phase III 162 employees were seen at the Birmingham Occupational Lung Disease clinic. 198 employees returned PEF records, including 141 of the 162 who attended for clinical investigation. Case definitions for diagnoses were agreed. 87 workers (10.4% of the workforce) met case definitions for occupational lung disease, comprising EAA (n = 19), occupational asthma (n = 74) and humidifier fever (n = 7). 12 workers had more than one diagnosis. The peak onset of work-related breathlessness was Spring 2003. The proportion of workers affected was higher for those using MWF from a large sump (27.3%) than for those working all over the manufacturing area (7.9%) (OR = 4.39, p<0.001). Two workers had positive specific provocation tests to the used but not the unused MWF solution. Extensive investigation of the outbreak of EAA detected a large number of affected workers, not only with EAA but also occupational asthma. This is the largest reported outbreak in Europe. Mist from used MWF is the likely cause. In workplaces using MWF there is a need to carry out risk assessments, to monitor and maintain fluid quality, to control mist and to carry out respiratory health surveillance.

Entropy-as-a-Service: Unlocking the Full Potential of Cryptography.

PubMed

Vassilev, Apostol; Staples, Robert

2016-09-01

Securing the Internet requires strong cryptography, which depends on the availability of good entropy for generating unpredictable keys and accurate clocks. Attacks abusing weak keys or old inputs portend challenges for the Internet. EaaS is a novel architecture providing entropy and timestamps from a decentralized root of trust, scaling gracefully across diverse geopolitical locales and remaining trustworthy unless much of the collective is compromised.

Effects of an amylopectin and chromium complex on the anabolic response to a suboptimal dose of whey protein.

PubMed

Ziegenfuss, T N; Lopez, H L; Kedia, A; Habowski, S M; Sandrock, J E; Raub, B; Kerksick, C M; Ferrando, A A

2017-01-01

Previous research has demonstrated the permissive effect of insulin on muscle protein kinetics, and the enhanced insulin sensitizing effect of chromium. In the presence of adequate whole protein and/or essential amino acids (EAA), insulin has a stimulatory effect on muscle protein synthesis, whereas in conditions of lower blood EAA concentrations, insulin has an inhibitory effect on protein breakdown. In this study, we determined the effect of an amylopectin/chromium (ACr) complex on changes in plasma concentrations of EAA, insulin, glucose, and the fractional rate of muscle protein synthesis (FSR). Using a double-blind, cross-over design, ten subjects (six men, four women) consumed 6 g whey protein + 2 g of the amylopectin-chromium complex (WPACr) or 6 g whey protein (WP) after an overnight fast. FSR was measured using a primed, continuous infusion of ring-d 5 -phenylalanine with serial muscle biopsies performed at 2, 4, and 8 h. Plasma EAA and insulin were assayed by ion-exchange chromatography and ELISA, respectively. After the biopsy at 4 h, subjects ingested their respective supplement, completed eight sets of bilateral isotonic leg extensions at 80% of their estimated 1-RM, and a final biopsy was obtained 4 h later. Both trials increased EAA similarly, with peak levels noted 30 min after ingestion. Insulin tended ( p  = 0.09) to be higher in the WPACr trial. Paired samples t-tests using baseline and 4-h post-ingestion FSR data separately for each group revealed significant increases in the WPACr group (+0.0197%/h, p  = 0.0004) and no difference in the WP group (+0.01215%/hr, p  = 0.23). Independent t-tests confirmed significant ( p  = 0.045) differences in post-treatment FSR between trials. These data indicate that the addition of ACr to a 6 g dose of whey protein (WPACr) increases the FSR response beyond what is seen with a suboptimal dose of whey protein alone.

Body Weight Loss and Tissue Wasting in Late Middle-Aged Mice on Slightly Imbalanced Essential/Non-essential Amino Acids Diet.

PubMed

Corsetti, Giovanni; Pasini, Evasio; Romano, Claudia; Calvani, Riccardo; Picca, Anna; Marzetti, Emanuele; Flati, Vincenzo; Dioguardi, Francesco S

2018-01-01

Objective: Inadequate protein intake can impair protein balance thus leading to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets, with various EAA/NEAA blends, on body composition and the risk of developing tissue wasting in late middle-aged male mice. Methods: Six groups of late middle-aged male mice were fed for 35 days with iso-nutrients, iso-caloric, and iso-nitrogenous special diets containing different EAA/NEAA ratios ranging from 100/0% to 0/100%. One group fed with standard laboratory rodent diet (StD) served as control. Preliminarily, we verified the palatability of the diets by recording the mice preference, and by making accessible all diets simultaneously, in comparison to StD. Body weight, food and water consumption were measured every 3 days. Blood and urine samples, as well as heart, kidneys, liver, spleen, triceps surae, retroperitoneal WAT, and BAT were harvested and weighed. Results: Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, the diet containing a EAA/NEAA-imbalance, with moderate NEAAs prevalence, was able to induce catabolic stimuli, generalized body wasting, and systemic metabolic alterations comparable to those observed with diet containing NEAA alone. In addition, complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-containing diets induced significant decreases in body weight by reducing primarily fat reserves, but at the same time they improved the clinical parameters. On these basis we can deduce that tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Conclusion: Our results indicate that diets containing an optimized balance of AA composition is necessary for preserving overall body energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates, including body wasting.

Digestion and nutrient net fluxes across the rumen, and the mesenteric- and portal-drained viscera in sheep fed with fresh forage twice daily: net balance and dynamic aspects.

PubMed

Rémond, Didier; Bernard, Laurence; Chauveau, Béatrice; Nozière, Pierre; Poncet, Claude

2003-05-01

Digestion and portal net flux of nutrients were studied in sheep fed twice daily with fresh orchard-grass. Digestive flows were measured in six fistulated sheep using the double-marker technique. Three sheep were fitted with catheters and blood-flow probes, allowing nutrient net flux measurements across the portal-drained viscera (PDV), the mesenteric-drained viscera (MDV) and the rumen. Total tract apparent digestion of N was similar to portal net appearance of N, calculated as the sum of free amino acids (FAA), peptide amino acids (PAA), NH3, and urea net fluxes. PAA accounted for 25 % of non-protein amino acid net release across the PDV. With the exception of glycine and glutamate, the small intestine was the main contributor to this PAA net release. The essential amino acid (EAA) apparent disappearance between the duodenum and the ileum was lower than the net appearance of EAA (FAA + PAA) across the MDV. The value of PDV:MDV flux of free EAA was, on average, 78 %. The rumen accounted for 30 % of the net uptake of EAA by the PDV tissues not drained by the mesenteric vein. Rumen net release of acetate, propionate, butyrate, 3-hydroxybutyrate, and lactate accounted for 70, 55, 46, 77 and 52 %, respectively, of their portal net releases. Conversely, the small intestine was a net consumer of arterial acetate and 3-hydroxybutyrate. Dynamic study of nutrient net fluxes across the PDV showed that throughout a feeding cycle, the liver faced a constant flux of amino acids (AA), whereas volatile fatty acid and NH3 net fluxes varied in response to the meal. The present study specified, in forage-fed sheep, the partitioning of nutrient net fluxes across the PDV and the role of peptides in portal net release of AA.

Entropy-as-a-Service: Unlocking the Full Potential of Cryptography

PubMed Central

Vassilev, Apostol; Staples, Robert

2016-01-01

Securing the Internet requires strong cryptography, which depends on the availability of good entropy for generating unpredictable keys and accurate clocks. Attacks abusing weak keys or old inputs portend challenges for the Internet. EaaS is a novel architecture providing entropy and timestamps from a decentralized root of trust, scaling gracefully across diverse geopolitical locales and remaining trustworthy unless much of the collective is compromised. PMID:28003687

Improved plasma amino acids pattern following 12 months of supplemented low-protein diet in peritoneal dialysis patients.

PubMed

Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Cao, Liou; Wang, Qin; Ni, Zhaohui; Lindholm, Bengt; Axelsson, Jonas; Yao, Qiang

2010-07-01

Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

Associations of Genetic Risk Score with Obesity and Related Traits and the Modifying Effect of Physical Activity in a Chinese Han Population

PubMed Central

Zhu, Jingwen; Loos, Ruth J. F.; Lu, Ling; Zong, Geng; Gan, Wei; Ye, Xingwang; Sun, Liang; Li, Huaixing; Lin, Xu

2014-01-01

Background/Objectives Recent large-scale genome-wide association studies have identified multiple loci robustly associated with BMI, predominantly in European ancestry (EA) populations. However, associations of these loci with obesity and related traits have not been well described in Chinese Hans. This study aimed to investigate whether BMI-associated loci are, individually and collectively, associated with adiposity-related traits and obesity in Chinese Hans and whether these associations are modified by physical activity (PA). Subjects/Methods We genotyped 28 BMI-associated single nucleotide polymorphisms (SNPs) in a population-based cohort including 2,894 unrelated Han Chinese. Genetic risk score (GRS), EA and East Asian ancestry (EAA) GRSs were calculated by adding BMI-increasing alleles based on all, EA and EAA identified SNPs, respectively. Interactions of GRS and PA were examined by including the interaction-term in the regression model. Results Individually, 26 of 28 SNPs showed directionally consistent effects on BMI, and associations of four loci (TMEM18, PCSK1, BDNF and MAP2K5) reached nominal significance (P<0.05). The GRS was associated with increased BMI, trunk fat and body fat percentages; and increased risk of obesity and overweight (all P<0.05). Effect sizes (0.11 vs. 0.17 kg/m2) and explained variance (0.90% vs. 1.45%) of GRS for BMI tended to be lower in Chinese Hans than in Europeans. The EA GRS and EAA GRS were associated with 0.11 and 0.13 kg/m2 higher BMI, respectively. In addition, we found that PA attenuated the effect of the GRS on BMI (P interaction = 0.022). Conclusions Our observations suggest that the combined effect of obesity-susceptibility loci on BMI tended to be lower in Han Chinese than in EA. The overall, EA and EAA GRSs exert similar effects on adiposity traits. Genetic predisposition to increased BMI is attenuated by PA in this population of Han Chinese. PMID:24626232

Evaluation of Automatically Quantified Foveal Avascular Zone Metrics for Diagnosis of Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

PubMed

Lu, Yansha; Simonett, Joseph M; Wang, Jie; Zhang, Miao; Hwang, Thomas; Hagag, Ahmed M; Huang, David; Li, Dengwang; Jia, Yali

2018-05-01

To describe an automated algorithm to quantify the foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), and to compare its performance for diagnosis of diabetic retinopathy (DR) and association with best-corrected visual acuity (BCVA) to that of extrafoveal avascular area (EAA). We obtained 3 × 3-mm macular OCTA scans in diabetic patients with various levels of DR and healthy controls. An algorithm based on a generalized gradient vector flow (GGVF) snake model detected the FAZ, and metrics assessing FAZ size and irregularity were calculated. We compared the automated FAZ segmentation to manual delineation and tested the within-visit repeatability of FAZ metrics. The correlations of two conventional FAZ metrics, two novel FAZ metrics, and EAA with DR severity and BCVA, as determined by Early Treatment Diabetic Retinopathy Study (ETDRS) charts, were assessed. Sixty-six eyes from 66 diabetic patients and 19 control eyes from 19 healthy participants were included. The agreement between manual and automated FAZ delineation had a Jaccard index > 0.82, and the repeatability of automated FAZ detection was excellent in eyes at all levels of DR severity. FAZ metrics that incorporated both FAZ size and shape irregularity had the strongest correlation with clinical DR grade and BCVA. Of all the tested OCTA metrics, EAA had the greatest sensitivity in differentiating diabetic eyes without clinical evidence of retinopathy, mild to moderate nonproliferative DR (NPDR), and severe NPDR to proliferative DR from healthy controls. The GGVF snake algorithm tested in this study can accurately and reliably detect the FAZ, using OCTA data at all DR severity grades, and may be used to obtain clinically useful information from OCTA data regarding macular ischemia in patients with diabetes. While FAZ metrics can provide clinically useful information regarding macular ischemia, and possibly visual acuity potential, EAA measurements may be a better biomarker for DR.

Automated Quantification of Nonperfusion Areas in 3 Vascular Plexuses With Optical Coherence Tomography Angiography in Eyes of Patients With Diabetes.

PubMed

Hwang, Thomas S; Hagag, Ahmed M; Wang, Jie; Zhang, Miao; Smith, Andrew; Wilson, David J; Huang, David; Jia, Yali

2018-06-14

Diabetic retinopathy (DR) is a leading cause of vision loss that is managed primarily through qualitative clinical examination of the retina. Optical coherence tomography angiography (OCTA) may offer an objective and quantitative method of evaluating DR. To quantify capillary nonperfusion in 3 vascular plexuses in the macula of eyes patients with diabetes of various retinopathy severity using projection-resolved OCTA (PR-OCTA). Cross-sectional study at a tertiary academic center comprising 1 eye each from healthy control individuals and patients with diabetes at different severity stages of retinopathy. Data were acquired and analyzed between January 2015 and December 2017. Foveal avascular zone area, extrafoveal avascular area (EAA), and the sensitivity of detecting levels of retinopathy. The study included 39 control individuals (20 women [51%]; mean [SD] age, 43.41 [19.37] years); 16 patients with diabetes without retinopathy (8 women [50%]; mean [SD] age, 56.50 [12.43] years); 23 patients with mild to moderate nonproliferative DR (18 women [78%] ; mean [SD] age, 62.48 [10.55] years); and 32 patients with severe nonproliferative DR or proliferative DR (12 women [38%]; mean age, 53.41 [14.05] years). Mean (SD) foveal avascular zone area was 0.203 (0.103) mm2 for control individuals, 0.192 (0.084) mm2 for patients with diabetes without retinopathy, 0.243 [0.079] mm2 for mild to moderate nonproliferative DR, and 0.359 (0.275) mm2 for severe nonproliferative DR or proliferative DR. Mean (SD) EAA in whole inner retinal slab in these groups, respectively, were 0.020 (0.031) mm2, 0.034 (0.047) mm2, 0.038 (0.040) mm2, and 0.237 (0.235) mm2. The mean (SD) sum of EAA from 3 segmented plexuses in each of the respective groups were 0.103 (0.169) mm2, 0.213 (0.242) mm2, 0.451 (0.243) mm2, and 1.325 (1.140) mm2. With specificity fixed at 95%, using EAA in inner retinal slab, the sensitivity of detecting patients with diabetes from healthy control individuals was 28% (95% CI, 18%-40%), 31% for patients with DR (95% CI, 19%-45%), and 47% for patients with severe DR (95% CI, 29%-65%) from whole inner retinal EAA. With the sum of EAA from 3 individual plexuses, the sensitivities were 69% (95% CI, 57%-80%), 82% (95% CI, 70%-91%), and 97% (95% CI, 85%-100%), respectively. Avascular areas were not associated with signal strength index. The commercial vessel density from the 2-plexus scheme distinguished the groups with lower sensitivity and were dependent on SSI. Automatically quantified avascular areas from a 3-layer segmentation scheme using PR-OCTA distinguished levels of retinopathy with a greater sensitivity than avascular areas from unsegmented inner retinal slab or measurements from a commercially available vessel density in 2-layer scheme. Additional studies are needed to investigate the applicability of nonperfusion parameters in clinical settings.

[Extrinsic allergic alveolitis (extrinsic allergic broncho- alveolitis, pneumopathies with precipitins, hypersensitivity pneumopathies)].

PubMed

Bonnaud, F

1986-01-01

The author does a general survey on this subject. Having evoked the EAA history, he describes the clinical syndrome with 3 forms (sharp to chronic). He relates in a first part, the main forms linked with rural occupation, from farmer's lung disease, the most frequent, to illnesses dues to cereals, woods exposition, then the one in touch with industry as coffee workers disease, and breeders of silkworms. At last, the ones in connection with urban activities as air-conditioner disease. These descriptions ended with EAA caused by a drug. Having evoked the complementary investigations necessary for diagnosis, he insists on the alveolitis washing and biochemicals studies. In conclusion, the author insists on the interest of steroids treatment in attacks.

Pulmonary stretch receptor afferents activate excitatory amino acid receptors in the nucleus tractus solitarii in rats.

PubMed

Bonham, A C; Coles, S K; McCrimmon, D R

1993-05-01

1. The goal of the present study was to identify potential neurotransmitter candidates in the Breuer-Hering (BH) reflex pathway, specifically at synapses between the primary afferents and probable second-order neurones (pump cells) within the nucleus tractus solitarii (NTS). We hypothesized that if activation of specific receptors in the NTS is required for production of the BH reflex, then (1) injection of the receptor agonist(s) would mimic the reflex response (apnoea), (2) injection of appropriate antagonists would impair the apnoea produced by either lung inflation or agonist injection, and (3) second-order neurones in the pathway would be excited by either lung inflation or agonists while antagonists would prevent the response to either. 2. Studies were carried out either in spontaneously breathing or in paralysed, thoracotomized and ventilated rats in which either diaphragm EMG or phrenic nerve activity, expired CO2 concentration and arterial pressure were continuously monitored. The BH reflex was physiologically activated by inflating the lungs. 3. Pressure injections (0.03-15 pmol) of selective excitatory amino acid (EAA) receptor agonists, quisqualic acid (Quis) and N-methyl-D-aspartic acid (NMDA) into an area of the NTS shown previously to contain neurones required for production of the BH reflex produced dose-dependent apnoeas that mimicked the response to lung inflation. Injection of substance P (0.03-4 pmol) did not alter baseline respiratory pattern. 4. Injections of the EAA antagonists, kynurenic acid (Kyn; 0.6-240 pmol), 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the BH region of the NTS reversibly impaired the apnoea produced by lung inflation. All three antagonists reduced or abolished the apnoeas resulting from injection of Quis or NMDA, and slowed baseline respiratory frequency. In contrast, injections of the highly selective NMDA receptor antagonist, D-2-amino-5-phosphonovaleric acids (AP5), in doses sufficient to block the apnoeic response to NMDA, neither altered the reflex apnoea evoked by lung inflation nor the baseline respiratory pattern. 5. Pump cells located within the BH region were excited by pressure injections of the broad spectrum EAA agonist, DL-homocysteic acid (DLH). Kyn reversibly blocked the excitation of pump cells in response to either lung inflation or DLH injection. 6. These findings suggest that EAAs mediate primary afferent excitation of second-order neurones in the Breuer-Hering reflex pathway, primarily through the activation of non-NMDA EAA receptor subtypes.

Efficacy of the Essential Amino Acids and Keto-Analogues on the CKD progression rate in real practice in Russia - city nephrology registry data for outpatient clinic.

PubMed

Zemchenkov, Alexander; Konakova, Irina N

2016-07-07

Renal replacement therapy (RRT) is growing by 10 % per year in Russia, but pre-dialysis care which can retard CKD progression and delay the start of RRT remains limited. We evaluate the effect of Essential Amino Acids and Keto-analogues (EAA/KA) on CKD progression. The effect of low protein diet (LPD), supplemented by EAA/KA, on GFR slope changes between first and second treatment period (five sequential visits per period) in 96 patients withs CKD Stage 3B-5 was compared to GFR slope changes in the control group of 96 patients, randomly selected from matched (by gender, age, diagnosis and CKD Stage) cohort of 320 patients from the city Registry. The mean baseline eGFR was 23 ± 9 ml/min/1.73 m2; 29 % had CKD3B, 45 % - CKD4, 26 % - CKD5. The rate of eGFR decline changed from -2.71 ± 2.38 to -2.01 ± 2.26 ml/min/1.73 m2 per year in the treatment group and from -2.18 ± 2.01 to -2.04 ± 2.18 ml/min/1.73 m2 per year in the control group. Only in the treatment group the difference was significant (p = 0.04 and p = 0.6). Standardized effect size for intervention was significant in treatment group: -0.3 (of pooled SD), 95 % CI -0.58 ÷  -0.02 and non-significant in control group: -0.07 (-0.35 ÷ +0.22). The univariate and multivariate analysis of EAA/KA therapy effect demonstrated that it was probably more effective in patients of older age, with higher time-averaged proteinuria (PU), lower phosphate level, in patients with glomerular v. interstitial diseases, and in females. Only the latter factor was significant at pre-specified level (<0.05). LPD combined with EAA/KA supplementation lead to the decrease of the CKD progression both in well-designed clinical study and in real nephrology practice in wide variety diseases and settings. Registry data can be helpful to reveal patients with optimal chances for beneficial effect of LPD supplemented by EAA/KA. ISRCTN28190556 06/05/2016.

Tree-based modeling of complex interactions of phosphorus loadings and environmental factors.

PubMed

Grunwald, S; Daroub, S H; Lang, T A; Diaz, O A

2009-06-01

Phosphorus (P) enrichment has been observed in the historic oligotrophic Greater Everglades in Florida mainly due to P influx from upstream, agriculturally dominated, low relief drainage basins of the Everglades Agricultural Area (EAA). Our specific objectives were to: (1) investigate relationships between various environmental factors and P loads in 10 farm basins within the EAA, (2) identify those environmental factors that impart major effects on P loads using three different tree-based modeling approaches, and (3) evaluate predictive models to assess P loads. We assembled thirteen environmental variable sets for all 10 sub-basins characterizing water level management, cropping practices, soils, hydrology, and farm-specific properties. Drainage flow and P concentrations were measured at each sub-basin outlet from 1992-2002 and aggregated to derive monthly P loads. We used three different tree-based models including single regression trees (ST), committee trees in Bagging (CTb) and ARCing (CTa) modes and ten-fold cross-validation to test prediction performances. The monthly P loads (MPL) during the monitoring period showed a maximum of 2528 kg (mean: 103 kg) and maximum monthly unit area P loads (UAL) of 4.88 kg P ha(-1) (mean: 0.16 kg P ha(-1)). Our results suggest that hydrologic/water management properties are the major controlling variables to predict MPL and UAL in the EAA. Tree-based modeling was successful in identifying relationships between P loads and environmental predictor variables on 10 farms in the EAA indicated by high R(2) (>0.80) and low prediction errors. Committee trees in ARCing mode generated the best performing models to predict P loads and P loads per unit area. Tree-based models had the ability to analyze complex, non-linear relationships between P loads and multiple variables describing hydrologic/water management, cropping practices, soil and farm-specific properties within the EAA.

Book Review: Encyclopedia of Astronomy and Astrophysics. Volumes 1-4

NASA Technical Reports Server (NTRS)

Maran, Stephen Paul

2001-01-01

This massive reference work (hereafter EAA) summarizes a great deal of what we knew in the astronomical sciences at the most recent Millennium. An associated website may keep much of it up-to-date for years to come. The contents are extensive indeed: the index alone consists of 76 pages, each with three columns of fine-type listings, and there are 'nearly 700 main articles'. The main articles are what make EAA worthwhile. They are generally by experts, who took much care in their preparation. The degree to which the articles are illustrated and referenced, however, seems to depend on the inclination of the individual author. On the other hand, articles on Saturn's rings and on its satellites are heavily illustrated, but with just two or three citations in each. The coverage of solar physics is especially thorough in EAA. There are numerous articles on major topics, notably in the physics and phenomena of the corona and the chromosphere, and some on more specialized areas, such as 'Polar Plumes' and 'Coronal Cavities.'

Postprandial portal fluxes of essential amino acids, volatile fatty acids, and urea-nitrogen in growing pigs fed a high-fiber diet supplemented with a multi-enzyme cocktail.

PubMed

Agyekum, A K; Kiarie, E; Walsh, M C; Nyachoti, C M

2016-09-01

The present study investigated the effects of adding a multi-enzyme cocktail (MC) to a high-fiber diet on net portal-drained viscera (PDV) fluxes of essential AA (EAA), volatile fatty acids (VFA), and blood urea-N (BUN) in growing pigs. Five female pigs (22.8 ± 1.6 kg BW), with catheters in the portal vein, ileal vein, and carotid artery, were fed 3 isocaloric-nitrogenous diets at 4% of their BW once daily at 0900 h for 7 d in a replicated 3 × 3 Latin square design. The diets contained corn and soybean meal with 0% (control) or 30% distillers' dried grains with solubles (DDGS; HF) produced from a 1:1 mixture of wheat and corn. The third diet was supplemented with MC in addition to the 30% DDGS (HF + MC). The MC supplied (analyzed values) 5,397 U of xylanase, 162 U of β-glucanase, and 2,000 U of protease and guaranteed minimum activities of 1,000 U of α-amylase and 25 U of pectinase per kg of diet. On d 7, para-amino hippuric acid was infused into the ileal vein (to measure flow rate), and blood was sampled from the portal vein and carotid artery for 7 h after feeding to assay EAA, urea-N, and VFA. Portal absorption of nutrients was derived by multiplying the porto-arterial plasma concentration differences by portal vein blood flow. Diet had no effect on postprandial portal vein plasma flow rate and net BUN flux, but portal BUN tended to be lower ( = 0.070) and arterial BUN was lower ( 0.05) over the 7 h in pigs fed control. Postprandial portal Arg, Ile, Leu, Trp, and Val or net fluxes were lower ( 0.05) in HF-fed pigs from 30 to 240 min than control-fed pigs and MC supplementation tended (0.05 ≤ ≤ 0.10) to or improved ( 0.05) portal appearances of those AA, but not their fluxes. Control-fed pigs had higher ( 0.05) net portal fluxes of most EAA and pigs fed HF + MC had higher ( 0.05) Lys, and similar Met and Phe net portal fluxes were compared with control-fed pigs. Portal VFA was not affected by diet. However, total portal VFA flux was lower ( 0.05) in the HF-fed pigs than in the control pigs. The MC supplementation improved the total portal VFA flux, although it did not improve arterial VFA concentration relative to the HF diet. In conclusion, supplementing the HF diet with MC improved net portal appearance of some EAA and fluxes of total VFA, whereas fluxes of EAA did not change. The HF diet increased EAA demand by the PDV, but MC addition was not able to reduce this demand.

Changes in mammary metabolism in response to the provision of an ideal amino acid profile at 2 levels of metabolizable protein supply in dairy cows: Consequences on efficiency.

PubMed

Haque, M N; Guinard-Flament, J; Lamberton, P; Mustière, C; Lemosquet, S

2015-06-01

The aim of this study was to compare the modifications in mammary gland metabolism by supplying an ideal versus an imbalanced essential AA (EAA) profile at low and high metabolizable protein (or PDIE, its equivalent in the INRA feeding system). Four lactating, multiparous Holstein cows received 4 treatments composed of 2 basal diets containing 2 levels of PDIE (LP or HP) and 2 different infusions of AA mixtures (AA- or AA+) in the duodenum. The AA+ mixture contained Lys, Met, Leu, His, Ile, Val, Phe, Arg, Trp, and Glu, whereas the AA- mixture contained Glu, Pro, and Ser. The infusion mixtures were iso-PDIE. The diet plus infusions provided 13.9 versus 15.8% of crude protein that corresponded to 102 versus 118g/kg of dry matter of PDIE in LP and HP treatments, respectively. The treatments were designed as a 2×2 crossover design of 2 levels of PDIE supply (LP vs. HP) with 28-d periods. Infusions of AA in the duodenum (AA- vs. AA+) were superimposed to diet within each 28-d period according to 2×2 crossover designs with 14-d subperiods. Increasing the PDIE supply tended to increase milk protein yield; however, the efficiency of PDIE utilization decreased and the plasma urea concentration increased, indicating a higher catabolism of AA. The AA+ treatments increased milk protein yield and content similarly at both levels of protein supply. This was explained by an increase in the mammary uptake of all EAA except His and Trp. The mammary uptake of non-EAA (NEAA) was altered to the increase in EAA uptake so that the total AA uptake was almost equal to milk protein output on a nitrogen basis. The ratio between NEAA to total AA uptake decreased from 46% in LPAA- to 40% in LPAA+, HPAA-, and HPAA+ treatments. The PDIE efficiency tended to increase in the AA+ versus the AA- treatments because the NEAA supply and the amount of NEAA not used by the mammary both decreased. Nevertheless, our AA+ treatments seemed not to be the ideal profile: the mammary uptake-to-output ratio for Thr was higher than 1 in LPAA-, but it decreased to 1 in all the other treatments, suggesting that Thr was deficient in these treatments. Conversely, an excess of His was indicated because its uptake was similar in AA+ and AA- treatments. In conclusion, balancing the EAA profile increased milk protein yield and metabolizable protein efficiency at both levels of protein supply by increasing the mammary uptake of EAA and altering the NEAA uptake, leading to less AA available for catabolism. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Metabolic advantages of higher protein diets and benefits of dairy foods on weight management, glycemic regulation, and bone.

PubMed

Pasiakos, Stefan M

2015-03-01

The Inst. of Medicine and World Health Organization have determined that 0.8 to 0.83 g protein·kg(-1) ·d(-1) is the quantity of protein required to establish nitrogen balance in nearly all healthy individuals. However, consuming higher protein diets may be metabolically advantageous, particularly for overweight and obese adults attempting weight loss, and for physically active individuals such as athletes and military personnel. Studies have demonstrated that higher protein diets may spare lean body mass during weight loss, promote weight management, enhance glycemic regulation, and increase intestinal calcium absorption, which may result in long-term improvements in bone health. The extent to which higher protein diets are beneficial is largely attributed to the digestive and absorptive properties, and also to the essential amino acid (EAA) content of the protein. Proteins that are rapidly digested and absorbed likely contribute to the metabolic advantages conferred by consuming higher protein diets. The EAA profiles, as well as the digestive and absorptive properties of dairy proteins, such as whey protein and casein, are particularly advantageous because they facilitate a rapid, robust, and sustained delivery of EAAs to the periphery. This article reviews the scientific literature assessing metabolic advantages associated with higher protein diets on weight management, glycemic regulation, and bone, with emphasis given to studies evaluating the potential benefits associated with dairy. © 2015 Institute of Food Technologists®

The role of inserted polymers in polymeric insulation materials: insights from QM/MD simulations.

PubMed

Li, Chunyang; Zhao, Hong; Zhang, Hui; Wang, Ying; Wu, Zhijian; Han, Baozhong

2018-02-28

In this study, we performed a quantum chemical molecular dynamics (QM/MD) simulation to investigate the space charge accumulation process in copolymers of polyethylene (PE) with ethylene acrylic acid (EAA), ethylene vinyl acetate (EVA), styrene-ethylene-butadiene-styrene (SEBS), and black carbon (BC). We predicted that BC, especially branched BC, would possess the highest electron affinity and is identified as the most promising filler in power cable insulation. Following incorporations of 0-4 high-energy electrons into the composites, branched BC exhibited the highest stability and almost all electrons were trapped by it. Therefore, PE was protected efficiently and BC can be considered as an efficient filler for high voltage cables and an inhibitor of tree formation. On the contrary, although EAA, EVA, and SEBS can trap high-energy electrons, the latter can be supersaturated in composites of EAA, EVA, and SEBS with PE. The inserted polymers was unavoidably destroyed following C-H and C-O bond cleavage, which results from the interactions and charge transfer between PE and inserted polymers. The content effects of -COOH, benzene, and -OCOCH 3 groups on the electron trapping, mobility and stability of PE were also investigated systematically. We hope this knowledge gained from this work will be helpful in understanding the role of inserted polymers and the growth mechanisms of electrical treeing in high voltage cable insulation.

Correlation of deglutition in subacute ischemic stroke patients with peripheral blood adaptive immunity: Essential amino acid improvement.

PubMed

Aquilani, Roberto; Emilio, Benevolo; Dossena, Maurizia; Baiardi, Paola; Testa, Amidio; Boschi, Federica; Viglio, Simona; Iadarola, Paolo; Pasini, Evasio; Verri, Manuela

2015-12-01

We aimed to document in stroke patients peripheral blood immune cell profiles, their relations with neuro-functional tests, and any possible influence of supplemented essential amino acids (EAAs) may have on both the immune system and the relationship of the latter with neuro-function.Forty-two dysphagic stroke patients (27 men; 71±9 years) underwent bio-humoral measurements, neuro-functional tests, including Functional Independence Measure (FIM) and Dysphagia Outcome and Severity Scale (DOSS), and were randomized to receive EAAs 8 g/d (EAA group) or isocaloric maltodextrin (placebo group).At discharge all measurements were repeated 38±1 days after randomization.At admission, total white cell (TWC), neutrophil (N), and lymphocyte (Lymph) counts were normal and the N/Lymph ratio was higher than normal values (<3.0). At discharge, both TWC and N decreased while Lymph increased significantly. As a result, the N/Lymph ratio significantly decreased (P <0.001) returning to normal levels. Absolute Lymph counts and Lymph % TWC correlated positively with DOSS (r = +0.235, P = 0.04 and r = +0.224, P = 0.05, respectively), negatively with C-reactive protein natural logarithm (ln CRP) (P = 0.02 and P = 0.0001, respectively), which is an inflammation marker. N correlated positively with ln CRP (P = 0.001) and had a slight negative association with FIM (P = 0.07). The N/Lymph ratio was inversely related to FIM (r = -0.262, P = 0.02) and DOSS (r = -0.279, P = 0.01). Finally, FIM correlated with DOSS (r = +0.35, P = 0.05).For the regression analysis, the overtime changes of Lymph % TWC correlated significantly with DOSS (P = 0.01). There was a positive correlation between Lymph % TWC and DOSS for the entire stroke population (P = 0.015). While this correlation was not important for the placebo group (P = 0.27), it was significant in the EAA subgroup (P = 0.018).In the sub-acute stroke stage, there may be slight alterations of peripheral blood immune cells. Lymph cells are associated with improved neuro-function tests with evidence that this association is enhanced by supplementing EAAs. © The Author(s) 2015.

Dietary protein in urea cycle defects: How much? Which? How?

PubMed

Boneh, Avihu

2014-01-01

Dietary recommendations for patients with urea cycle disorders (UCDs) are designed to prevent metabolic decompensation (primarily hyperammonaemia), and to enable normal growth. They are based on the 'recommended daily intake' guidelines, on theoretical considerations and on local experience. A retrospective dietary review of 28 patients with UCDs in good metabolic control, at different ages, indicates that most patients can tolerate a natural protein intake that is compatible with metabolic stability and good growth. However, protein aversion presents a problem in many patients, leading to poor compliance with the prescribed daily protein intake. These patients are at risk of chronic protein deficiency. Failing to recognise this risk, and further restricting protein intake because of persistent hyperammonaemia may aggravate the deficiency and potentially lead to episodes of metabolic decompensation for which no clear cause is found. These patients may need on-going supplementation with essential amino acids (EAA) to prevent protein malnutrition. Current recommendations for the management of acute metabolic decompensation include cessation of protein intake whilst increasing energy (calorie) intake in the first 24h. We have found that plasma concentrations of all EAA are low at the time of admission to hospital for metabolic decompensation, with correlation between low EAA concentrations, particularly branched-chain amino acids, and hyperammonaemia. Thus, supplementation with EAA should be considered at times of metabolic decompensation. Finally, it would be advantageous to treat patients in metabolic decompensation through enteral supplementation, whenever possible, because of the contribution of the splanchnic (portal-drained viscera) system to protein retention and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Sulfate threshold target to control methylmercury levels in wetland ecosystems

USGS Publications Warehouse

Corrales, J.; Naja, G.M.; Dziuba, C.; Rivero, R.G.; Orem, W.

2011-01-01

Sulfate contamination has a significant environmental implication through the stimulation of toxic hydrogen sulfide and methylmercury (MeHg) production. High levels of MeHg are a serious problem in many wetland ecosystems worldwide. In the Florida Everglades, it has been demonstrated that increasing MeHg occurrence is due to a sulfate contamination problem. A promising strategy of lowering the MeHg occurrence is to reduce the amount of sulfate entering the ecosystem. High surface water sulfate concentrations in the Everglades are mainly due to discharges from the Everglades Agricultural Area (EAA) canals. Water and total sulfur mass balances indicated that total sulfur released by soil oxidation, Lake Okeechobee and agricultural application were the major sources contributing 49,169, 35,217 and 11,775mtonsyear-1, respectively. Total sulfur loads from groundwater, levees, and atmospheric deposition contributed to a lesser extent: 4055; 5858 and 4229mtonsyear-1, respectively. Total sulfur leaving the EAA into Water Conservation Areas (WCAs) through canal discharge was estimated at 116,360mtonsyear-1, and total sulfur removed by sugarcane harvest accounted for 23,182mtonsyear-1. Furthermore, a rise in the mineral content and pH of the EAA soil over time, suggested that the current rates of sulfur application would increase as the buffer capacity of the soil increases. Therefore, a site specific numeric criterion for sulfate of 1mgL-1 was recommended for the protection of the Everglades; above this level, mercury methylation is enhanced. In parallel, sulfide concentrations in the EAA exceeded the 2??gL-1 criterion for surface water already established by the U.S. Environmental Protection Agency (EPA). ?? 2011 Elsevier B.V.

Nutritional status of outpatients with chronic stable heart failure based on serum amino acid concentration.

PubMed

Tsuji, Shuhei; Koyama, Satoshi; Taniguchi, Ryoji; Fujiwara, Takako; Fujiwara, Hisayoshi; Sato, Yukihito

2018-06-06

Loss of skeletal muscle mass and low nutritional status are major complications of severe chronic heart failure (CHF) and have been associated with poor prognosis. This study aimed to identify the nutritional status of outpatients with CHF based on their body composition, such as skeletal muscle index (SMI) and serum amino acid concentration. We compared the body composition data and results of blood samples, including the serum amino acid concentration, of patients with CHF and those of controls. No significant difference was found in total amino acid concentration between 105 patients with CHF (62% men, mean age: 71.0±11.0 years) and 106 controls (67% men, mean age: 69.1±9.4 years) (CHF: 3459.1±504.9nmol/ml, control: 3575.8±513.1nmol/ml; p=0.072). However, the concentration of essential amino acids (EAA) (CHF: 949.5±197.9nmol/ml, control: 1034.1±207.3nmol/ml; p=0.002) and branched-chain amino acid (BCAA) (CHF: 449.3±114.3nmol/ml, control: 503.9±118.2nmol/ml; p<0.001) and Fischer's ratio (CHF: 2.86±0.62, control: 3.17±0.50; p<0.001) were significantly lower in patients with CHF. Integrated analysis of these data revealed that SMI was negatively correlated with age [correlation coefficient (R), -0.313; 95% confidence interval (CI), -0.514 to -0.079; p=0.010], but positively correlated with EAA concentration (R, 0.256; 95% CI, 0.017-0.467; p=0.037), BCAA concentration (R, 0.362; 95% CI, 0.134-0.554; p=0.003), and Fischer's ratio (R, 0.573; 95% CI, 0.386-0.715; p<0.001). Serum concentrations of EAA and BCAA and Fischer's ratio were lower in patients with CHF than in controls, while SMI correlated with EAA, BCAA, and Fischer's ratio. Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Ability of commercially available dairy ration programs to predict duodenal flows of protein and essential amino acids in dairy cows.

PubMed

Pacheco, D; Patton, R A; Parys, C; Lapierre, H

2012-02-01

The objective of this analysis was to compare the rumen submodel predictions of 4 commonly used dairy ration programs to observed values of duodenal flows of crude protein (CP), protein fractions, and essential AA (EAA). The literature was searched and 40 studies, including 154 diets, were used to compare observed values with those predicted by AminoCow (AC), Agricultural Modeling and Training Systems (AMTS), Cornell-Penn-Miner (CPM), and National Research Council 2001 (NRC) models. The models were evaluated based on their ability to predict the mean, their root mean square prediction error (RMSPE), error bias, and adequacy of regression equations for each protein fraction. The models predicted the mean duodenal CP flow within 5%, with more than 90% of the variation due to random disturbance. The models also predicted within 5% the mean microbial CP flow except CPM, which overestimated it by 27%. Only NRC, however, predicted mean rumen-undegraded protein (RUP) flows within 5%, whereas AC and AMTS underpredicted it by 8 to 9% and CPM by 24%. Regarding duodenal flows of individual AA, across all diets, CPM predicted substantially greater (>10%) mean flows of Arg, His, Ile, Met, and Lys; AMTS predicted greater flow for Arg and Met, whereas AC and NRC estimations were, on average, within 10% of observed values. Overpredictions by the CPM model were mainly related to mean bias, whereas the NRC model had the highest proportion of bias in random disturbance for flows of EAA. Models tended to predict mean flows of EAA more accurately on corn silage and alfalfa diets than on grass-based diets, more accurately on corn grain-based diets than on non-corn-based diets, and finally more accurately in the mid range of diet types. The 4 models were accurate at predicting mean dry matter intake. The AC, AMTS, and NRC models were all sufficiently accurate to be used for balancing EAA in dairy rations under field conditions. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Examining the effect of dietary electrolyte balance, energy source, and length of feeding of nitrogen-free diets on ileal endogenous amino acid losses in broilers.

PubMed

Adedokun, S A; Pescatore, A J; Ford, M J; Jacob, J P; Helmbrecht, A

2017-09-01

The effect of dietary electrolyte balance (DEB), energy source (ES), and length of feeding of nitrogen-free diet (NFD) on ileal endogenous amino acid (EAA) loss in mg/kg dry matter intake (DMI) was evaluated in broiler chickens. In Experiment 1, 720 chickens consisting of 15 replicate cages with 6 chickens/replicate were used. Treatments were arranged in a 2 × 2 × 2 factorial and consisted of 4 NFD with 2 levels (low or high) of DEB and 2 ES [corn starch (CS) or dextrose (DX)], and 2 sampling time-points (diets were fed for either 72 h (d 16 to 19) or 120 h (d 16 to 21). Experiment 2 used 360 chickens in a 2 × 2 factorial arrangement of treatments with 2 levels (low or high) of DEB and 2 ES (CS or DX). Diets were fed for 72 h (d 18 to 21). All birds had access to feed and water on an ad libitum basis. Data were analyzed using the GLM procedure of SAS appropriate for a completely randomized design for a factorial arrangement of treatments. For Experiment 1, there were interactions (P < 0.05) between the 3 main factors for nitrogen and all the AA except Trp. Broilers that were fed DX-based NFD with high DEB for 72 h had the highest (P < 0.05) EAA losses. In Experiment 2, there was no interaction between DEB and ES except for His and Lys. When ileal EAA losses from birds fed the low DEB, CS-based NFD were used to standardize apparent ileal digestibility values from a previous study, there was no effect of length of feeding on standardized ileal AA digestibility values. In conclusion, DX-based NFD with high DEB increased endogenous AA loses. Despite differences in ileal EAA losses from CS-based NFD, standardized ileal AA digestibility values were not influenced by the length of feeding of NFD. Based on the results from these studies, NFD could be fed for 72 h without influencing SIAAD values. © 2017 Poultry Science Association Inc.

Aging and health: Self-efficacy for Self-direction in Health Scale.

PubMed

Oliveira, Albertina L; Silva, José T; Lima, Margarida P

2016-07-04

To validate the Escala de Autoeficácia para a Autodireção na Saúde (EAAS - Self-efficacy for Self-direction in Health Scale). Non-experimental quantitative study of EAAS validation, by confirmatory factorial analyses, evaluating a sample of 508 older adults from the north and the center of Portugal with mean age of 71.67 (from 51 to 96 years), to whom the Self-efficacy for Self-direction in Health Scale, the Rosenberg Self-esteem Scale, the Positive and Negative Affect Schedule, the Satisfaction with Life Scale, and the Instrumental Activities of Daily Living Scale were applied. The EAAS was developed from the theoretical constructs of self-efficacy and from self-directed learning within the PALADIN European project framework, aiming to develop an instrument able to assess the extent to which older adults take good care of their health. The internal consistency was 0.87 (Cronbach's alpha) and confirmatory factorial analyses enabled to find a model near the one theoretically proposed, indicating a structure consisting of four dimensions: physical exercise, healthy diet, engaging in health-related learning, and visits to health professionals. From the psychometric point of view, the model in four factors showed quite satisfactory fit indicators. The Self-efficacy for Self-direction in Health Scale, with 16 items, is adequate to evaluate to what extent older adults have confidence in their ability to take care of their own health, with high degree of autonomy. Validar a Escala de Autoeficácia para a Autodireção no domínio da Saúde (EAAS). Estudo quantitativo não experimental de validação da EAAS, por meio de análises fatoriais confirmatórias, avaliando amostra de 508 seniores e idosos provenientes das regiões Norte e Centro de Portugal com média etária de 71.67 (51 a 96 anos), a quem foram aplicadas a Escala de Autoeficácia para a Autodireção na Saúde, a Escala de Autoestima de Rosenberg, a Escala de Afeto Positivo e Afeto Negativo, a Escala de Satisfação Com a Vida e a escala de Atividades Instrumentais da Vida Diária. A EAAS foi desenvolvida a partir dos construtos teóricos da autoeficácia e da aprendizagem autodirigida no âmbito do projeto europeu PALADIN, visando constituir um instrumento apto a avaliar até que ponto os seniores cuidam bem da sua saúde. A consistência interna encontrada foi de 0.87 (alfa de Cronbach) e as análises fatoriais confirmatórias permitiram encontrar um modelo próximo ao proposto teoricamente, indicando uma estrutura constituída por quatro dimensões: exercício físico, alimentação saudável, envolvimento em aprendizagens relativas à saúde e visitas a profissionais de saúde. Do ponto de vista psicométrico, o modelo em quatro fatores mostrou indicadores de ajustamento bastante satisfatórios. A Escala de Autoeficácia para a Autodireção na Saúde, com 16 itens, é adequada para avaliar em que medida os seniores têm confiança na sua capacidade para tomar conta da própria saúde, com elevado grau de autonomia.

Functional cardiovascular action of L-cysteine microinjected into pressor sites of the rostral ventrolateral medulla of the rat.

PubMed

Takemoto, Yumi

2014-04-01

The endogenous sulfur-containing amino acid L-cysteine injected into the cerebrospinal fluid space of the cisterna magna increases arterial blood pressure (ABP) and heart rate (HR) in the freely moving rat. The present study examined (1) cardiovascular responses to L-cysteine microinjected into the rostral ventrolateral medulla (RVLM), where a group of neurons regulate activities of cardiovascular sympathetic neurons and (2) involvement of ionotropic excitatory amino acid (iEAA) receptors in response. In the RVLM of urethane-anesthetized rats accessed ventrally and identified with pressor responses to L-glutamate (10 mM, 34 nl), microinjections of L-cysteine increased ABP and HR dose dependently (3-100 mM, 34 nl). The cardiovascular responses to L-cysteine (30 mM) were not attenuated by a prior injection of either antagonist alone, MK801 (20 mM, 68 nl) for the NMDA type of iEAA receptors, or CNQX (2 mM) for the non-NMDA type. However, inhibition of both NMDA and non-NMDA receptors with additional prior injection of either antagonist completely blocked those responses to L-cysteine. The results indicate that L-cysteine has functional cardiovascular action in the RVLM of the anesthetized rat, and the responses to L-cysteine involve both NMDA and non-NMDA receptors albeit in a mutually exclusive parallel fashion. The findings may suggest endogenous roles of L-cysteine indirectly via iEAA receptors in the neuronal network of the RVLM for cardiovascular regulation in physiological and pathological situations.

Novel Antigen Identification Method for Discovery of Protective Malaria Antigens by Rapid Testing of DNA Vaccines Encoding Exons from the Parasite Genome

DTIC Science & Technology

2004-03-01

EAA21673 1,443 — — Xeroderma pigmentosum G N&I region, helix-hairpin-helix class P.f., P.k., P.b., P.v. PY02286 EAA21722 696 — — Hypothetical protein...ND PY01828 Gene gun 0.1 2,560 640 Pos IM 0.1 Neg Neg ND CSP Gene gun 0.1 2,560 Neg Neg IM 2.7* 2,560 Neg ND a Parasite burden in liver is in...negative; Pos , positive; ND, not done. c Sera tested at a single dilution (1:80). VOL. 72, 2004 DISCOVERY OF PROTECTIVE MALARIA PARASITE ANTIGENS 1599

Sugarcane Responses to Water-Table Depth and Periodic Flood

USDA-ARS?s Scientific Manuscript database

Sugarcane (Saccharum spp.) is routinely exposed to periodic floods and shallow water tables in Florida’s Everglades Agricultural Area (EAA). The purpose of this study was to examine the yields and juice quality of four sugarcane cultivars (CP 88-1762, CP 89-2143, CP 89-2376, and CP 96-1252) maintain...

Effects of Equine Assisted Activities on Autism Spectrum Disorder

ERIC Educational Resources Information Center

Lanning, Beth A.; Baier, Margaret E. Matyastik; Ivey-Hatz, Julie; Krenek, Nancy; Tubbs, Jack D.

2014-01-01

Quality of life assessments were used in this study to determine the behavioral changes of children diagnosed with autism spectrum disorder (ASD) who participated in equine assisted activities. Behavioral changes of children with ASD participating in 9 weeks of equines assisted activities (EAA) (N = 10) were compared to behavioral changes of…

Extrinsic allergic alveolitis caused by misting fountains.

PubMed

Koschel, Dirk; Stark, Wolfram; Karmann, Fritz; Sennekamp, Jochen; Müller-Wening, Dietrich

2005-08-01

Recently, an increasing number of patients were presented to our clinics with febrile and respiratory symptoms associated with exposure to a new type of domestic ultrasonic humidifier. We report on 11 patients who developed recurrent episodes of fever, cough and dyspnea after repeated exposure to ultrasonic misting fountains at home. A diagnosis of extrinsic allergic alveolitis (EAA) or toxic alveolitis was made on the basis of the history and the clinical, radiological, laboratory and immunological findings. Eight patients were subjected to inhalative challenge tests with their own ultrasonic misting fountains, and all of them exhibited positive reactions. Nine patients were diagnosed with an EAA (humidifier lung) and two patients with a toxic alveolitis (humidifier fever). This study demonstrates the potential for ultrasonic misting fountains to cause illness in the home. In view of the increasing popularity of these devices, humidifier lung and humidifier fever should be considered in the differential diagnosis of patients with unexplained pulmonary or flu-like illnesses with fever.

Phosphorus and water budgets in an agricultural basin.

PubMed

Faridmarandi, Sayena; Naja, Ghinwa M

2014-01-01

Water and phosphorus (P) budgets of a large agricultural basin located in South Florida (Everglades Agricultural Area, EAA) were computed from 2005 to 2012. The annual surface outflow P loading from the EAA averaged 157.2 mtons originating from Lake Okeechobee (16.4 mtons, 10.4%), farms (131.0 mtons, 83.4%), and surrounding basins (9.8 mtons, 6.2%) after attenuation. Farms, urban areas, and the adjacent C-139 basin contributed 186.1, 15.6, and 3.8 mtons/yr P to the canals, respectively. The average annual soil P retention was estimated at 412.5 mtons. Water and P budgets showed seasonal variations with high correlation between rainfall and P load in drainage and surface outflows. Moreover, results indicated that the canals acted as a P sink storing 64.8 mtons/yr. To assess the P loading impact of farm drainage on the canals and on the outflow, dimensionless impact factors were developed. Sixty-two farms were identified with a high and a medium impact factor I1 level contributing 44.5% of the total drainage P load to the canals, while their collective area represented less than 23% of the EAA area (172 farms). Optimizing the best management practice (BMP) strategies on these farms could minimize the environmental impacts on the downstream sensitive wetlands areas.

METABOLIC RESPONSES TO DIETARY LEUCINE RESTRICTION INVOLVE REMODELING OF ADIPOSE TISSUE AND ENHANCED HEPATIC INSULIN SIGNALING

PubMed Central

Wanders, Desiree; Stone, Kirsten P.; Dille, Kelly; Simon, Jacob; Pierse, Alicia; Gettys, Thomas W.

2015-01-01

Dietary leucine was incrementally restricted to test whether limiting this essential amino acid (EAA) would fully reproduce the beneficial responses produced by dietary methionine restriction. Restricting leucine by 85% increased energy intake and expenditure within five to seven days of its introduction and reduced overall accumulation of adipose tissue. Leucine restriction (LR) also improved glucose tolerance, increased hepatic release of FGF21 into the blood stream, and enhanced insulin-dependent activation of Akt in liver. However, LR had no effect on hepatic lipid levels and failed to lower lipogenic gene expression in the liver. LR did affect remodeling of white and brown adipose tissue, increasing expression of both thermogenic and lipogenic genes. These findings illustrate that dietary LR reproduces many but not all of the physiological responses of methionine restriction. The primary differences occur in the liver, where methionine and leucine restriction cause opposite effects on tissue lipid levels and expression of lipogenic genes. Together these findings suggest that the sensing systems which detect and respond to dietary restriction of EAAs act through mechanisms that both leucine and methionine are able to engage, and in the case of hepatic lipid metabolism, may be unique to specific EAAs such as methionine. PMID:26643647

Effects of an Equine Assisted Activities Program on Youth with Emotional Disturbance: A Pilot Study

ERIC Educational Resources Information Center

Stebbins, Tira

2012-01-01

This study evaluated the effects of a 10-week Equine Assisted Activities (EAA) program on special education students (aged 9 to 15) identified as Emotionally Disturbed (ED) who were enrolled in an alternative school. A control group of special education students receiving treatment-as-usual was included. The Behavior Assessment Scale for Children,…

Sulfur and Methylmercury in the Florida Everglades - the Biogeochemical Connection

NASA Astrophysics Data System (ADS)

Orem, W. H.; Gilmour, C. C.; Krabbenhoft, D. P.; Aiken, G.

2011-12-01

Methylmercury (MeHg) is a serious environmental problem in aquatic ecosystems worldwide because of its toxicity and tendency to bioaccumulate. The Everglades receives some of the highest levels of atmospheric mercury deposition and has some of the highest levels of MeHg in fish in the USA, posing a threat to pisciverous wildlife and people through fish consumption. USGS studies show that a combination of biogeochemical factors make the Everglades especially susceptible to MeHg production and bioaccumulation: (1) vast wetland area with anoxic soils supporting anaerobic microbial activity, (2) high rates of atmospheric mercury deposition, (3) high levels of dissolved organic carbon (DOC) that complexes and stabilizes mercury in solution for transport to sites of methylation, and (4) high sulfate loading in surface water that drives microbial sulfate reduction and mercury methylation. The high levels of sulfate in the Everglades represent an unnatural condition. Background sulfate levels are estimated to be <1 mg/L, but about 60% of the Everglades has surface water sulfate concentrations exceeding background. Highly sulfate-enriched marshes in the northern Everglades have average sulfate levels of 60 mg/L. Sulfate loading to the Everglades is principally a result of land and water management in south Florida. The highest concentrations of sulfate, averaging 60-70 mg/L, are in canal water in the Everglades Agricultural Area (EAA). Geochemical data and a preliminary sulfur mass balance for the EAA are consistent with sulfur currently used in agriculture, and sulfur released by oxidation of organic EAA soils (including legacy agricultural applications and natural sulfur) as the primary sources of sulfate enrichment to the canals and ecosystem. Sulfate loading increases microbial sulfate reduction and MeHg production in soils. The relationship between sulfate loading and MeHg production, however, is complex. Sulfate levels up to about 20-30 mg/L increase mercury methylation, but buildup of sulfide from microbial sulfate reduction begins to inhibit mercury methylation above this range. Sulfate from the EAA canals has primarily impacted the northern Everglades nearest the EAA, but recent evidence shows sulfate loading extending about 80 km further south into Everglades National Park. Current restoration plans to restore to deliver more water south to Everglades National Park may increase overall sulfur loads to the southern part of the ecosystem. A comprehensive Everglades restoration strategy should include reduction of sulfur loads as a goal because of the many detrimental impacts of sulfate on the ecosystem. Monitoring data show that the ecosystem response to changes in sulfate levels is rapid, and strategies for reducing sulfate loading may be effective in the near-term. A multifaceted approach employing best management practices for sulfur in agriculture, agricultural practices that minimize soil oxidation, and changes to stormwater treatment areas that increase sulfate retention, could help reduce sulfate loads to the Everglades, with resulting benefits.

Sulfur in the South Florida ecosystem: Distribution, sources, biogeochemistry, impacts, and management for restoration

USGS Publications Warehouse

Orem, W.; Gilmour, C.; Axelrad, D.; Krabbenhoft, D.; Scheidt, D.; Kalla, P.; McCormick, P.; Gabriel, M.; Aiken, G.

2011-01-01

Sulfur is broadly recognized as a water quality issue of significance for the freshwater Florida Everglades. Roughly 60% of the remnant Everglades has surface water sulfate concentrations above 1 mg l-1, a restoration performance measure based on present sulfate levels in unenriched areas. Highly enriched marshes in the northern Everglades have average sulfate levels of 60 mg l-1. Sulfate loading to the Everglades is principally a result of land and water management in South Florida. The highest concentrations of sulfate (average 60-70 mg l-1) in the ecosystem are in canal water in the Everglades Agricultural Area (EAA). Potential sulfur sourcesin the watershed are many, but geochemical data and a preliminary sulfur mass balance for the EAA are consistent with sulfur presently used in agricultural, and sulfur released by oxidation of organic EAA soils (including legacy agricultural applications and natural sulfur) as the primary sources of sulfate enrichment in the EAA canals. Sulfate loading to the Everglades increases microbial sulfate reduction in soils, leading to more reducing conditions, greater cycling of nutrients in soils, production of toxic sulfide, and enhanced methylmercury (MeHg) production and bioaccumulation. Wetlands are zones of naturally high MeHg production, but the combination of high atmospheric mercury deposition rates in South Florida and elevated sulfate loading leads to increased MeHg production and MeHg risk to Everglades wildlife and human consumers. Sulfate from the EAA drainage canals penetrates deep into the Everglades Water Conservation Areas, and may extend into Everglades National Park. Present plans to restore sheet flow and to deliver more water to the Everglades may increase overall sulfur loads to the ecosystem, and move sulfate-enriched water further south. However, water management practices that minimize soil drying and rewetting cycles can mitigate sulfate release during soil oxidation. A comprehensive Everglades restoration strategy should include reduction of sulfur loads as a goal because of the many detrimental impacts of sulfate on the ecosystem. Monitoring data show that the ecosystem response to changes in sulfate levels is rapid, and strategies for reducing sulfate loading may be effective in the near term. A multifaceted approach employing best management practices for sulfur in agriculture, agricultural practices that minimize soil oxidation, and changes to stormwater treatment areas that increase sulfate retention could help achieve reduced sulfate loads to the Everglades, with resulting benefits. Copyright ?? 2011 Taylor & Francis Group, LLC.

Efficient phosphorus management practices in the Everglades Agricultural Area

NASA Astrophysics Data System (ADS)

Bhadha, J. H.; Lang, T. A.; Daroub, S. H.; Alvarez, O.; Tootoonchi, M.; Capasso, J.

2016-12-01

In the 450,000 acres of the Everglades Agricultural Area (EAA) of South Florida, farming practices have long been mindful of phosphorus (P) management as it relates to sufficiency and efficiency of P utilization. Over two decades of P best management practices have resulted in 3001 metric-ton of P load reduction from the EAA to downstream ecosystems. During the summer, more than 50,000 acres of fallow sugarcane land is available for rice production. The net value of growing flooded rice in the EAA as a rotational crop with sugarcane far exceeds its monetary return. Soil conservation, improvement in tilth and P load reduction are only some of the benefits. With no P fertilizer applied, a two-year field trial on flooded rice showed improved outflow P concentrations by up to 40% as a result of particulate setting and plant P uptake. Harvested whole grain rice can effectively remove a significant amount of P from a rice field per growing season. In parts of the EAA where soils are sandy, the application of using locally derived organic amendments as potential P fertilizer has gained interest over the past few years. The use of local agricultural and urban organic residues as amendments in sandy soils of South Florida provide options to enhance soil properties and improve sugarcane yields, while reducing waste and harmful effects of agricultural production on the environment. A lysimeter study conducted to determine the effect of mill ash and three types of biochar (rice hulls, yard waste, horse bedding) on sugarcane yields, soil properties, and drainage water quality in sandy soils showed that mill ash and rice hull biochar increased soil TP, Mehlich 3-P (M3-P), and cation exchange capacity (CEC) compared to the control. TP and M3-P content remained constant after 9 months, CEC showed a significant increase over time with rich hull biochar addition. Future projects include the utilization of aquatic vegetation, such as chara and southern naiad as bio-filters in farm ditches to reduce P load. This will be achieved by circulating high P concentration farm canal water through the ditches prior to being discharged off site. Optimizing the flow through the ditches will allow the aquatic vegetation to uptake P. The vegetation will ultimately be harvested and incorporated back on to the fields.

Elevate and Uterine Preservation: Two-Year Results.

PubMed

Stanford, Edward J; Moore, Robert D; Roovers, Jan-Paul W R; VanDrie, Douglas M; Giudice, Thomas P; Lukban, James C; Bataller, Eduardo; Sutherland, Suzette E

2015-01-01

To evaluate efficacy of the Elevate Anterior and Apical (EAA) in the repair of pelvic organ prolapse (POP) when performed after previous hysterectomy and with or without uterine preservation during POP surgery. One hundred forty-two women with anterior vaginal prolapse and/or apical descent ≥ stage II were enrolled. The primary outcome was treatment failure defined as > stage II POP-Q during follow-up using the Last observed Failure Carried Forward method. Three sub-groups were analysed: baseline previous hysterectomy (N = 61); concomitant hysterectomy (N = 29), and preserved uterus/no hysterectomy (N = 51). Demographics, primary and secondary outcomes, and extrusion were compared between the groups. A P value less than 0.05 was considered statistically significant. Anatomic success shows significant and durable improvement at 24 months. The success for the apical compartment ranged between 93.8% and 100%. Success was slightly lower for the anterior compartment (70.8-89.1%). No statistically significant difference between the 3 subgroups. Age was the only patient characteristic to be found different between the 3 subgroups. In addition, there was no difference in overall intraoperative complications (P = 0.263). Mesh extrusion was found in all groups: 3 of 61 (4.9%) had previous hysterectomy; 4 of 29 (13.8%) had concomitant hysterectomy; and 1 of 51 (2.0%) had uterus preserved (P = 0.094). There appears to be a trend toward higher extrusion when a hysterectomy was performed with the EAA. Anatomic success and complications for the EAA do not appear to be significantly impacted when the uterus is removed before or during surgery or preserved. There may be a trend toward increased mesh extrusion when a hysterectomy is performed. However, larger cohort studies are needed to determine if concomitant hysterectomy impact extrusion.

Effect of aspartate and asparagine supplementation on fatigue determinants in intense exercise.

PubMed

Marquezi, Marcelo Luis; Roschel, Hamilton Augusto; dos Santa Costa, André; Sawada, Letícia Aiko; Lancha, Antonio Herbert

2003-03-01

This study evaluated the effect of aspartate (ASP) and asparagine (ASG) supplementation on fatigue determinants in Wistar rats exercised to exhaustion by swimming. The animals were tested for anaerobic threshold (AT) determination and then supplemented with 350 mM ASP + 400 mM ASG x day(-1) (AA group, n = 16) or 2 ml x day(-1) of distillated water (PLC group, n = 16) for 7 days. On the 7th day of supplementation, the animals were divided into 4 new groups and killed at rest (RAA, n = 8; RPLC, n = 8), or immediately after the swimming exercise to exhaustion (EAA, n = 8; EPLC, n = 8). R: No significant differences were observed between amino acids and placebo rest groups for muscle and liver glycogen, blood glucose, lactate, alanine, and glutamine concentrations. However, in the exhaustion groups, the EAA group showed higher exercise time (68.37 +/- 25.42 x 41.12 +/- 13.82 min, p <.05) and lower blood lactate concentration (8.57 +/- 1.92 x 11.28 +/- 2.61 mmol x L(-1), p <.05) than the EPLC group. Moreover, the ASP+ASG supplementation decreased the rate of glycogen degradation of gastrocnemius (1.00 +/- 0.51 x 3.43 +/- 0.99 microg x 100 mg of tissue sample(-1) x min(-1), extensor digitorius longus (5.70 +/- 2.35 x 8.11 +/- 3.97 microg. 100 mg of tissue sample(-1) x min(-1) and liver (0.51 +/- 0.34 x 3.37 +/- 2.31 microg x 100 mg of tissue sample(-1) x min(-1) for EAA. These results suggest that ASP+ASG supplementation may increase the contribution of oxidative metabolism in energy production and delay fatigue during exercise performed above the AT.

Presynaptic Inhibition of Diverse Afferents to the Locus Coeruleus by Kappa Opiate Receptors: a Novel Mechanism for Regulating the Central Norepinephrine System

PubMed Central

Kreibich, Arati S.; Reyes, Beverly A. S.; Curtis, Andre L.; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J.; Valentino, Rita J.

2008-01-01

The norepinephrine nucleus, locus coeruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAA), corticotropin-releasing factor (CRF) and endogenous opioids acting at μ-opiate receptors. As the LC is also innervated by the endogenous κ-opiate receptor (κ-OR) ligand, dynorphin, and expresses κ-ORs, this study investigated κ-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of κ-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the κ-OR agonist, U50488, into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the κ-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that κ-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-NE system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate κ-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders or disorders characterized by abnormal sensory responses, such as autism. PMID:18562623

Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

PubMed

Kreibich, Arati; Reyes, Beverly A S; Curtis, Andre L; Ecke, Laurel; Chavkin, Charles; Van Bockstaele, Elisabeth J; Valentino, Rita J

2008-06-18

The norepinephrine nucleus, locus ceruleus (LC), is activated by diverse stimuli and modulates arousal and behavioral strategies in response to these stimuli through its divergent efferent system. Afferents communicating information to the LC include excitatory amino acids (EAAs), corticotropin-releasing factor (CRF), and endogenous opioids acting at mu-opiate receptors. Because the LC is also innervated by the endogenous kappa-opiate receptor (kappa-OR) ligand dynorphin and expresses kappa-ORs, this study investigated kappa-OR regulation of LC neuronal activity in rat. Immunoelectron microscopy revealed a prominent localization of kappa-ORs in axon terminals in the LC that also contained either the vesicular glutamate transporter or CRF. Microinfusion of the kappa-OR agonist (trans)-3,4-dichloro-N-methyl-N-[2-1-pyrrolidinyl)-cyclo-hexyl] benzeneacetamide (U50488) into the LC did not alter LC spontaneous discharge but attenuated phasic discharge evoked by stimuli that engage EAA afferents to the LC, including sciatic nerve stimulation and auditory stimuli and the tonic activation associated with opiate withdrawal. Inhibitory effects of the kappa-OR agonist were not restricted to EAA afferents, as U50488 also attenuated tonic LC activation by hypotensive stress, an effect mediated by CRF afferents. Together, these results indicate that kappa-ORs are poised to presynaptically inhibit diverse afferent signaling to the LC. This is a novel and potentially powerful means of regulating the LC-norepinephrine system that can impact on forebrain processing of stimuli and the organization of behavioral strategies in response to environmental stimuli. The results implicate kappa-ORs as a novel target for alleviating symptoms of opiate withdrawal, stress-related disorders, or disorders characterized by abnormal sensory responses, such as autism.

Equilibrium-point control of human elbow-joint movement under isometric environment by using multichannel functional electrical stimulation

PubMed Central

Matsui, Kazuhiro; Hishii, Yasuo; Maegaki, Kazuya; Yamashita, Yuto; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio

2014-01-01

Functional electrical stimulation (FES) is considered an effective technique for aiding quadriplegic persons. However, the human musculoskeletal system has highly non-linearity and redundancy. It is thus difficult to stably and accurately control limbs using FES. In this paper, we propose a simple FES method that is consistent with the motion-control mechanism observed in humans. We focus on joint motion by a pair of agonist-antagonist muscles of the musculoskeletal system, and define the “electrical agonist-antagonist muscle ratio (EAA ratio)” and “electrical agonist-antagonist muscle activity (EAA activity)” in light of the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, respectively, to extract the equilibrium point and joint stiffness from electromyography (EMG) signals. These notions, the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, are based on the hypothesis that the equilibrium point and stiffness of the agonist-antagonist motion system are controlled by the central nervous system. We derived the transfer function between the input EAA ratio and force output of the end-point. We performed some experiments in an isometric environment using six subjects. This transfer-function model is expressed as a cascade-coupled dead time element and a second-order system. High-speed, high-precision, smooth control of the hand force were achieved through the agonist-antagonist muscle stimulation pattern determined by this transfer function model. PMID:24987326

Equilibrium-point control of human elbow-joint movement under isometric environment by using multichannel functional electrical stimulation.

PubMed

Matsui, Kazuhiro; Hishii, Yasuo; Maegaki, Kazuya; Yamashita, Yuto; Uemura, Mitsunori; Hirai, Hiroaki; Miyazaki, Fumio

2014-01-01

Functional electrical stimulation (FES) is considered an effective technique for aiding quadriplegic persons. However, the human musculoskeletal system has highly non-linearity and redundancy. It is thus difficult to stably and accurately control limbs using FES. In this paper, we propose a simple FES method that is consistent with the motion-control mechanism observed in humans. We focus on joint motion by a pair of agonist-antagonist muscles of the musculoskeletal system, and define the "electrical agonist-antagonist muscle ratio (EAA ratio)" and "electrical agonist-antagonist muscle activity (EAA activity)" in light of the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, respectively, to extract the equilibrium point and joint stiffness from electromyography (EMG) signals. These notions, the agonist-antagonist muscle ratio and agonist-antagonist muscle activity, are based on the hypothesis that the equilibrium point and stiffness of the agonist-antagonist motion system are controlled by the central nervous system. We derived the transfer function between the input EAA ratio and force output of the end-point. We performed some experiments in an isometric environment using six subjects. This transfer-function model is expressed as a cascade-coupled dead time element and a second-order system. High-speed, high-precision, smooth control of the hand force were achieved through the agonist-antagonist muscle stimulation pattern determined by this transfer function model.

Growth and clinical variables in nitrogen-restricted piglets fed an adjusted essential amino acid mix: Effects using partially intact protein-based diets

USDA-ARS?s Scientific Manuscript database

Current recommendations for protein levels in infant formula ensure that growth matches or exceeds growth of breast-fed infants, but may provide a surplus of amino acids (AA). Recent studies in infants using AA-based formulas support specific adjustment of the essential AA (EAA) composition allowing...

Factors contributing to anaemia after uncomplicated falciparum malaria in under five year-old Nigerian children ten years following adoption of artemisinin-based combination therapies as first-line antimalarials.

PubMed

Sowunmi, Akintunde; Fatunmbi, Bayo; Akano, Kazeem; Wewe, Olubunmi A; Agomo, Chimere; Finomo, Finomo; Ebenebe, Joy; Jiya, Nma; Ambe, Jose; Wammanda, Robinson; Ntadom, Godwin; Mokuolu, Olugbenga; Emechebe, George; Ezeigwe, Nnenna; Ayede, Adejumoke I; Adewoye, Elsie O; Gbotosho, Grace O; Folarin, Onikepe A; Happi, Christian T; Oguche, Stephen; Oyibo, Wellington A; Useh, Francis

2017-12-19

Artemisinin-based combination therapies (ACTs) have remained efficacious treatments of acute falciparum malaria in many endemic areas but there is little evaluation of factors contributing to the anaemia of acute falciparum malaria following long term adoption of ACTs as first-line antimalarials in African children. Malarious <5 year-olds randomized to artemether-lumefantrine, artesunate-amodiaquine or dihydroartemisinin-piperaquine treatments were followed up clinically for 6 weeks. Anaemia was defined as haematocrit <30%; Malaria-attributable fall in haematocrit (MAFH) as the difference between haematocrit 28-42 days post- and pre-treatment; Total MAFH (TMAFH) as the difference between days 28-42 haematocrit and the lowest haematocrit recorded in the first week post-treatment initiation; Drug-attributable fall in haematocrit (DAFH) as the difference between MAFH and TMAFH; Early appearing anaemia (EAA) as haematocrit <30% occurring within 1 week in children with normal haematocrit pre-treatment. Predictors of anaemia pre-treatment, EAA, MAFH or DAFH >4% were evaluated by stepwise multiple logistic regression models. Survival analysis and kinetics of DAFH were evaluated by Kaplan-Meier estimator and non-compartment model, respectively. Pre-treatment, 355 of 959 children were anaemic. Duration of illness >2 days and parasitaemia ≤10,000 μL -1 were independent predictors of anaemia pre-treatment. EAA occurred in 301 of 604 children. Predictors of EAA were age ≤ 15 months, history of fever pre-treatment and enrolment haematocrit ≤35%. The probabilities of progression from normal haematocrit to EAA were similar for all treatments. MAFH >4% occurred in 446 of 694 children; its predictors were anaemia pre-treatment, enrolment parasitaemia ≤50,000 μL -1 , parasitaemia one day post-treatment initiation and gametocytaemia. DAFH >4% occurred in 334 of 719 children; its predictors were history of fever pre-and fever 1 day post-treatment initiation, haematocrit ≥37%, and parasitaemia >100,000 μL -1 . In 432 children, declines in DAFH deficits were monoexponential with overall estimated half-time of 2.2d (95% CI 1.9-2.6). Area under curve of deficits in DAFH versus time and estimated half-time were significantly higher in non-anaemic children indicating greater loss of haematocrit in these children. After ten years of adoption of ACTs, anaemia is common pre-and early post-treatment, falls in haematocrit attributable to a single infection is high, and DAFH >4% is common and significantly lower in anaemic compared to non-anaemic Nigerian children. Pan African Clinical Trial Registry (PACTR) [ PACTR201709002064150, 1 March 2017 ].

Trifunctional conjugation reagents. Reagents that contain a biotin and a radiometal chelation moiety for application to extracorporeal affinity adsorption of radiolabeled antibodies.

PubMed

Wilbur, D Scott; Chyan, Ming-Kuan; Hamlin, Donald K; Kegley, Brian B; Nilsson, Rune; Sandberg, Bengt E B; Brechbiel, Martin

2002-01-01

A method of removing radiolabeled monoclonal antibodies (mAbs) from blood using a device external to the body, termed extracorporeal affinity-adsorption (EAA), is being evaluated as a means of decreasing irradiation of noncancerous tissues in therapy protocols. The EAA device uses an avidin column to capture biotinylated-radiolabeled mAbs from circulated blood. In this investigation, three trifunctional reagents have been developed to minimize the potential deleterious effect on antigen binding brought about by the combination of radiolabeling and biotinylation of mAbs required in the EAA approach. The studies focused on radiolabeling with (111)In and (90)Y, so the chelates CHX-A' '-DTPA and DOTA, which form stable attachments to these radionuclides, were incorporated in the trifunctional reagents. The first trifunctional reagent prepared did not incorporate a group to block the biotin cleaving enzyme biotinidase, but the two subsequent reagents coupled aspartic acid to the biotin carboxylate for that purpose. All three reagents used 4,7,10-trioxa-1,13-tridecanediamine as water-soluble spacers between an aminoisophthalate core and the biotin or chelation group. The mAb conjugates were radioiodinated to evaluate cell binding as a function of substitution. Radioiodination was used so that a direct comparison with unmodified mAb could be made. Evaluation of the number of conjugates per antibody versus cell binding immunoreactivities indicated that minimizing the number of conjugates was best. Interestingly, a decrease of radioiodination yield as a function of the number of isothiocyanate containing conjugates per mAb was noted. The decreased yields were presumably due to the presence of thiourea functionality formed in the conjugation reaction. Radiolabeling with (111)In and (90)Y was facile at room temperature for conjugates containing the CHX-A' ', but elevated temperature (e.g., 45 degrees C) was required to obtain good yields with the DOTA chelate. Stability of (90)Y labeled mAb in serum, and when challenged with 10 mM EDTA, was high. However, challenging the (90)Y labeled mAb with 10 mM DTPA demonstrated high stability for the DOTA containing conjugate, but low stability for the CHX-A' ' containing conjugate. Thus, the choice between these two chelating moieties might be made on requirements for facile and gentle labeling versus very high in vivo stability. Application of the trifunctional biotinylation reagents to the blood clearance of labeled antibodies in EAA is under investigation. The new reagents may also be useful for other applications.

The role of agri-environment schemes in conservation and environmental management

PubMed Central

Batáry, Péter; Dicks, Lynn V; Kleijn, David; Sutherland, William J

2015-01-01

Over half of the European landscape is under agricultural management and has been for millennia. Many species and ecosystems of conservation concern in Europe depend on agricultural management and are showing ongoing declines. Agri-environment schemes (AES) are designed partly to address this. They are a major source of nature conservation funding within the European Union (EU) and the highest conservation expenditure in Europe. We reviewed the structure of current AES across Europe. Since a 2003 review questioned the overall effectiveness of AES for biodiversity, there has been a plethora of case studies and meta-analyses examining their effectiveness. Most syntheses demonstrate general increases in farmland biodiversity in response to AES, with the size of the effect depending on the structure and management of the surrounding landscape. This is important in the light of successive EU enlargement and ongoing reforms of AES. We examined the change in effect size over time by merging the data sets of 3 recent meta-analyses and found that schemes implemented after revision of the EU's agri-environmental programs in 2007 were not more effective than schemes implemented before revision. Furthermore, schemes aimed at areas out of production (such as field margins and hedgerows) are more effective at enhancing species richness than those aimed at productive areas (such as arable crops or grasslands). Outstanding research questions include whether AES enhance ecosystem services, whether they are more effective in agriculturally marginal areas than in intensively farmed areas, whether they are more or less cost-effective for farmland biodiversity than protected areas, and how much their effectiveness is influenced by farmer training and advice? The general lesson from the European experience is that AES can be effective for conserving wildlife on farmland, but they are expensive and need to be carefully designed and targeted. El Papel de los Esquemas Agro-Ambientales en la Conservación y el Manejo Ambiental Batáry et al. Resumen Más de la mitad de las tierras europeas está bajo manejo agrícola y así ha sido durante milenios. Muchas especies y ecosistemas de interés de conservación en Europa dependen del manejo agrícola y están mostrando una declinación continua. Los esquemas agro-ambientales (EAA) están diseñados en parte para encarar esto. Los esquemas son una gran fuente de financiamiento para la conservación dentro de la Unión Europea (UE) y el mayor gasto de conservación en Europa. Revisamos la estructura de los EAA actuales a lo largo del continente. Desde que en 2003 una revisión cuestionó la efectividad general de los EAA para la biodiversidad, ha habido una plétora de estudios de caso y meta-análisis que examinan su efectividad. La mayoría de las síntesis demuestran un incremento general en la biodiversidad de las tierras de cultivo en respuesta a los EAA, con la magnitud del efecto dependiente de la estructura y el manejo del terreno circundante. Esto es importante a la luz del crecimiento sucesivo de la UE y las continuas reformas a los EAA. Examinamos el cambio en la magnitud del efecto a través del tiempo al fusionar los conjuntos de datos de tres meta-análisis recientes y encontramos que los esquemas implementados después de la revisión de los programas agro-ambientales de la UE en 2007 no fueron más efectivos que los esquemas implementados antes de la revisión. Además, los esquemas enfocados en las áreas fuera de producción (como los márgenes de campo y los setos vivos) son más efectivos en el mejoramiento de la riqueza de especies que aquellos enfocados en las áreas productivas (como los cultivos arables y los pastizales). Las preguntas sobresalientes de la investigación incluyen si los EAA mejoran los servicios ambientales, si son más efectivos en las áreas agrícolas marginales que en las áreas de cultivo intensivo, si son más o menos rentables para la biodiversidad de las tierras de cultivo que las áreas protegidas, y en cuánto influye sobre su efectividad los consejos y el entrenamiento dado a los granjeros. La lección general de la experiencia europea es que los EAA pueden ser efectivos para la conservación de la vida silvestre en las tierras de cultivo, pero son caros y necesitan ser diseñados y enfocados cuidadosamente. PMID:25997591

Replacing dietary nonessential amino acids with ammonia nitrogen does not alter amino acid profile of deposited protein in the carcass of growing pigs fed a diet deficient in nonessential amino acid nitrogen.

PubMed

Mansilla, W D; Htoo, J K; de Lange, C F M

2017-10-01

Amino acid usage for protein retention, and, consequently, the AA profile of retained protein, is the main factor for determining AA requirements in growing animals. The objective of the present study was to determine the effect of supplementing ammonia N on whole-body N retention and the AA profile of retained protein in growing pigs fed a diet deficient in nonessential AA (NEAA) N. In total, 48 barrows with a mean initial BW of 13.6 kg (SD 0.7) were used. At the beginning of the study, 8 pigs were euthanized for determination of initial protein mass. The remaining animals were individually housed and fed 1 of 5 dietary treatments. A common basal diet (95% of experimental diets) was formulated to meet the requirements for all essential AA (EAA) but to be deficient in NEAA N (CP = 8.01%). The basal diet was supplemented (5%) with cornstarch (negative control) or 2 N sources (ammonia or NEAA) at 2 levels each to supply 1.35 or 2.70% extra CP. The final standardized ileal digestible (SID) NEAA content in the high-NEAA-supplemented diet (positive control) was based on the NEAA profile of whole-body protein of 20-kg pigs, and it was expected to reduce the endogenous synthesis of NEAA. Pigs were fed at 3.0 times maintenance energy requirements for ME in 3 equal meals daily. At the end of a 3-wk period, pigs were euthanized and the carcass and visceral organs were weighed, frozen, and ground for determination of protein mass. From pigs in the initial, negative control, high-ammonia, and high-NEAA groups, AA contents in the carcass and pooled visceral organs were analyzed to determine the total and deposited protein AA profile, dietary EAA efficiencies, and minimal de novo synthesis of NEAA. Carcass weight and whole-body N retention linearly increased ( < 0.05) with N supplementation. The AA profile of protein and deposited protein in the carcass was not different ( > 0.10) between N sources, but Cys content increased ( < 0.05) with NEAA compared with ammonia in visceral organ protein and deposited protein. The dietary SID EAA efficiency for increasing EAA deposition in whole-body protein increased ( < 0.05) with N supplementation, but it was not different ( > 0.10) between N sources. The de novo synthesis of NEAA increased ( < 0.05) for ammonia compared with NEAA supplementation. In conclusion, adding ammonia as a N source to diets deficient in NEAA N increases whole-body N retention without affecting the carcass AA profile.

31 CFR 587.304 - Information or informational materials.

Code of Federal Regulations, 2010 CFR

2010-07-01

... heading 9701, 9702, or 9703 of the Harmonized Tariff Schedule of the United States. (b) The term... the EAA to the extent that such controls promote the nonproliferation or antiterrorism policies of the...

In vivo protein quality of selected cereal-based staple foods enriched with soybean proteins.

PubMed

Acevedo-Pacheco, Laura; Serna-Saldívar, Sergio O

2016-01-01

One way to diminish protein malnutrition in children is by enriching cereal-based flours for the manufacturing of maize tortillas, wheat flour tortillas, and yeast-leavened breads, which are widely consumed among low socio-economic groups. The aim was to determine and compare the essential amino acid (EAA) scores, protein digestibility corrected amino acid scores (PDCAAS), and in vivo protein quality (protein digestibility, protein efficiency ratio (PER), biological values (BV), and net protein utilization (NPU) values) of regular versus soybean-fortified maize tortillas, yeast-leavened bread, and wheat flour tortillas. To comparatively assess differences in protein quality among maize tortillas, wheat flour tortillas, and yeast-leavened breads, EAA compositions and in vivo studies with weanling rats were performed. The experimental diets based on regular or soybean-fortified food products were compared with a casein-based diet. Food intake, weight gains, PER, dry matter and protein digestibility, BV, NPU, and PDCAAS were assessed. The soybean-fortified tortillas contained 6% of defatted soybean flour, whereas the yeast-leavened bread flour contained 4.5% of soybean concentrate. The soybean-fortified tortillas and bread contained higher amounts of lysine and tryptophan, which improved their EAA scores and PDCAAS. Rats fed diets based on soybean-fortified maize or wheat tortillas gained considerably more weight and had better BV and NPU values compared with counterparts fed with respective regular products. As a result, fortified maize tortillas and wheat flour tortillas improved PER from 0.73 to 1.64 and 0.69 to 1.77, respectively. The PER improvement was not as evident in rats fed the enriched yeast-leavened bread because the formulation contained sugar that decreased lysine availability possibly to Maillard reactions. The proposed enrichment of cereal-based foods with soybean proteins greatly improved PDCAAS, animal growth, nitrogen retention, and PER primarily in both maize and wheat flour tortillas. Therefore, these foods can help to diminish protein malnutrition among children who greatly depend on cereals as the main protein dietary source.

STEm Minority Graduate Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicholas, Kaen E

ABSTRACT The state of science, technology, engineering and math (STEM) education in the United States has seen some unfavorable assessments over the past decade. In early February, 2010 the House of Representatives heard testimony on undergraduate and graduate education. The message from the panel, which included experts from academia, STEM-based industries, and the National Science Foundation (NSF) was dire and required an urgent response. The experts along with the committee's chairperson, U. S. Representative Daniel Lipinski (D-IL) cited that the complexity of Science, Technology, Engineering, and Mathematics applications and coursework and the methodology utilized to teach these subjects are forcingmore » students out of these disciplines. As the National Academies described in its 2007 report Rising Above the Gathering Storm, successful STEM education is not just an academic pursuit it's a necessity for competing in the knowledge-based economy that the United States had a key role in creating. The potential for action is being made available again as the America COMPETES Act of 2007 is up for reauthorization. Its initial focus was on STEM education at the K-12 levels, but efforts at the undergraduate and graduate levels are needed to retain students to fill the jobs left vacant as baby boomers retire. The Educational Advancement Alliance, Inc. (EAA) has for two decades created programs that have not only addressed the issues of ensuring that students are aptly prepared for college but have focused its efforts over the past decade on increasing the number of students who pursue degrees in STEM disciplines. For the EAA, the introduction of the wonders of science begins at the elementary and middle school level via the Learning Lab, a state-of-the-art mobile science laboratory that visits students in grades 4-6 at the various schools throughout Philadelphia and The Math/Tech Academy which meets on Saturdays for students in grades 5-7. For the past two years the EAA has assisted college graduates in their quest to attain advanced degrees in STEM by providing fellowships. The EAA continued this effort by recruiting and providing fellowships to students who aspired to continue their education at the graduate level. The fellowships provided funding for tuition, fees, books, technology, and stipends to assist with room, board, and living expenses during the academic year and salary, transportation, and living expenses to those students who secured internships with the Department of Energy. Additionally the EAA designed and implemented needed support systems to ensure successful completion of the Masters degree programs, including but not limited to membership in professional associations, attendance at industry and academic conferences, and professional development workshops, and tutorial assistance if needed. This program assisted over 80 students directly and society-at-large by helping to educate and develop future physicists, engineers, biostatisticians, and researchers who will have the necessary skillsets to fill the increasing numbers of positions that require such expertise.« less

The Chemical Composition and Nitrogen Distribution of Chinese Yak (Maiwa) Milk

PubMed Central

Li, Haimei; Ma, Ying; Li, Qiming; Wang, Jiaqi; Cheng, Jinju; Xue, Jun; Shi, John

2011-01-01

The paper surveyed the chemical composition and nitrogen distribution of Maiwa yak milk, and compared the results with reference composition of cow milk. Compared to cow milk, yak milk was richer in protein (especially whey protein), essential amino acids, fat, lactose and minerals (except phosphorus). The contents of some nutrients (total protein, lactose, essential amino acids and casein) were higher in the warm season than in the cold season. Higher ratios of total essential amino acids/total amino acids (TEAA/TAA) and total essential amino acids/total non essential amino acids (TEAA/TNEAA) were found in the yak milk from the warm season. However its annual average ratio of EAA/TAA and that of EAA/NEAA were similar to those of cow milk. Yak milk was rich in calcium and iron (p < 0.05), and thus may serve as a nutritional ingredient with a potential application in industrial processing. PMID:21954332

Prediction of mechanical properties of composites of HDPE/HA/EAA.

PubMed

Albano, C; Perera, R; Cataño, L; Karam, A; González, G

2011-04-01

In this investigation, the behavior of the mechanical properties of composites of high-density polyethylene/hydroxyapatite (HDPE/HA) with and without ethylene-acrylic acid copolymer (EAA) as possible compatibilizer, was studied. Different mathematical models were used to predict their Young's modulus, tensile strength and elongation at break. A comparison with the experimental results shows that the theoretical models of Guth and Kerner modified can be used to predict the Young's modulus. On the other hand, the values obtained by the Verbeek model do not show a good agreement with the experimental data, since different factors that influence the mechanical properties are considered in this model such as: aspect ratio of the reinforcement, interfacial adhesion, porosity and binder content. TEM analysis confirms the discrepancies obtained between the experimental Young's modulus values and those predicted by the Verbeek model. The values of "P", "a" and "σ(A)" suggest that an interaction among the carboxylic groups of the copolymer and the hydroxyl groups of hydroxyapatite might be present. In composites with 20 and 30 wt% of filler, this interaction does not improve the Young's modulus values, since the deviations of the Verbeek model are significant. Copyright © 2010 Elsevier Ltd. All rights reserved.

Comparison in nutritional quality between wild and cultured cuttlefish Sepia pharaonis

NASA Astrophysics Data System (ADS)

Wen, Jing; Chen, Daohai; Zeng, Ling

2014-01-01

In this study, the proximate composition and the amino and fatty acid profiles of shrimp Litopenaeus vannamei (prey) and wild and cultured cuttlefish Sepia pharaonis (the latter fed the prey) were determined and compared with FAO/WHO recommendations. The resulting scores for isoleucine, phenylalanine+tyrosine, histidine, lysine, threonine, and tryptophan in cultured cuttlefish were ≥150. The ratio of EAA (essential amino acids)/nonessential amino acids in cultured cuttlefish (0.82) was higher than in the wild form (0.80). All EAA amino acid scores for cultured cuttlefish were higher than their wild counterparts, except for histidine and tryptophan. Both groups of cuttlefish possessed similar saturated fatty acid content, with the cultured containing much more total (Σ) monounsaturated fatty acids, Σ n-6 polyunsaturated fatty acids (PUFA), and eicosapentaenoic acid (C20:5 n-3) but less Σ n-3 PUFA, arachidonic acid (C20:4 n-6), and docosahexaenoic acid (C22:6 n-3) than their wild counterparts. Therefore, the present results suggest that these cultured cuttlefish were better than the wild form for human health. Notably, these results also indicate that the nutritional composition of these cuttlefish might have been significantly affected by diet.

Comparison of Free Total Amino Acid Compositions and Their Functional Classifications in 13 Wild Edible Mushrooms.

PubMed

Sun, Liping; Liu, Qiuming; Bao, Changjun; Fan, Jian

2017-02-24

Thirteen popular wild edible mushroom species in Yunnan Province, Boletus bicolor , Boletus speciosus , Boletus sinicus , Boletus craspedius , Boletus griseus , Boletus ornatipes , Xerocomus , Suillus placidus , Boletinus pinetorus , Tricholoma terreum , Tricholomopsis lividipileata , Termitomyces microcarpus , and Amanita hemibapha , were analyzed for their free amino acid compositions by online pre-column derivazation reversed phase high-performance liquid chromatography (RP-HPLC) analysis. Twenty free amino acids, aspartic acid, glutamic acid, serine, glycine, alanine, praline, cysteine, valine, methionine, phenylalanine, isoleucine, leucine, lysine, histidine, threonine, asparagines, glutamine, arginine, tyrosine, and tryptophan, were determined. The total free amino acid (TAA) contents ranged from 1462.6 mg/100 g in B. craspedius to 13,106.2 mg/100 g in T. microcarpus . The different species showed distinct free amino acid profiles. The ratio of total essential amino acids (EAA) to TAA was 0.13-0.41. All of the analyzed species showed high contents of hydrophobic amino acids, at 33%-54% of TAA. Alanine, cysteine, glutamine, and glutamic acid were among the most abundant amino acids present in all species. The results showed that the analyzed mushrooms possessed significant free amino acid contents, which may be important compounds contributing to the typical mushroom taste, nutritional value, and potent antioxidant properties of these wild edible mushrooms. Furthermore, the principal component analysis (PCA) showed that the accumulative variance contribution rate of the first four principal components reached 94.39%. Cluster analysis revealed EAA composition and content might be an important parameter to separate the mushroom species, and T. microcarpus and A. hemibapha showed remarkable EAA content among the 13 species.

[Photoacoustic spectroscopy evaluation of the impact of smoking on the composition of exhaled air in patients with bronchopulmonary diseases].

PubMed

Bukreeva, E B; Bulanova, A A; Kistenev, Yu V; Nikiforova, O Yu

To investigate the impact of smoking on the air exhaled by patients with chronic obstructive pulmonary disease (COPD) and asthmatics, by applying photoacoustic spectroscopy. The exhaled air absorption spectra (EAAS) were analyzed in healthy volunteers and patients with COPD and asthmatics, by applying an ILPA-1 CO2 laser photoacoustic gas analyzer. The procedure based on the calculation of an integrated estimate (IE) of the state of the object was used to assess the findings. Comparison of the IE of EAAS in COPD patients and non-smoking healthy individuals showed that spectra of the compounds, the formation of which was associated with smoking, were recorded in the range of wavelengths corresponding to the 10R branch of CO2 laser generation. This also provided evidence indicating that the exhaled air of asthmatics differed from that of both smoking and non-smoking healthy individuals. The calculations yielded the threshold values of EAAS IE in the range of wavelengths corresponding to the 10P branche of CO2 laser generation, which made it possible to distinguish non-smoking healthy individuals from asthmatics and COPD patients in 94 and 89% of cases, respectively. The investigation has confirmed that smoking substantially impacts the composition of the air exhaled by healthy individuals. It has been shown that the use of reference groups formed from non-smoking healthy individuals can improve the accuracy of photoacoustic spectroscopy in detecting COPD and asthma. A further development in this direction will open up new prospects for a new method to diagnose COPD and asthma.

Effect of ascorbic acid or increasing metabolizable energy level with or without supplementation of some essential amino acids on productive and physiological traits of slow-growing chicks exposed to chronic heat stress.

PubMed

Attia, Y A; Hassan, R A; Tag El-Din, A E; Abou-Shehema, B M

2011-12-01

Four hundred and twenty, 21-day-old slow-growing chicks were divided randomly into seven treatments, each containing five replicates. Each replicate was kept in a 1 × 1-m floor pen. One treatment was kept under thermo-neutral conditions in a semi-open house and fed a corn-soybean meal diet (positive control). The other six groups were kept under chronic heat stress (CHS) at 38 °C and 60% RH for 4 h from 12:00 to 16:00 pm for three successive days per week. Chicks in CHS treatments were fed a corn-soybean meal diet without (negative control) or with increasing metabolizable energy (ME) level by oil supplementation alone, or also with increasing some essential amino acids (EAA) such as methionine (Met), methionine and lysine (Met+Lys) or methionine, lysine and arginine (Met+Lys+Arg) or supplemented with 250 mg of ascorbic acid (AA)/kg. CHS impaired (p < 0.05) growth performance, increased plasma triglycerides and total serum Ca while decreasing (p < 0.05) plasma glucose and total serum protein. Meanwhile 250 mg AA/kg diet or an increasing ME without or with some EAA partially alleviated (p < 0.0001) the negative effect of CHS on growth while increasing (p < 0.05) feed intake and improving (p < 0.05) feed:gain ratio (F:G) and crude protein (CP) digestibility (p < 0.05). AA or increasing ME with or without EAA increased (p < 0.05) percentage dressing, liver and giblets to those of the positive control. AA or increasing ME with or without EAA partially alleviated the negative effect of CHS on blood pH, packed cell volume (PCV), haemoglobin (Hgb), total serum protein and total Ca, plasma glucose and triglyceride, rectal temperature and respiration rate. Increasing ME level improved chickens' tolerance to CHS without a significant difference from those supplemented with AA. However, increasing Met, Lys and Arg concentration did not improve performance over that recorded with increasing ME level alone. Under CHS, 250 mg AA/kg diet or increasing ME level by addition of 3% vegetable oil could be an useful approach to improve productive and physiological traits of slow-growing chicks, which may be applicable also to fast-growing one. © 2010 Blackwell Verlag GmbH.

Cardiovascular actions of L-cysteine and L-cysteine sulfinic acid in the nucleus tractus solitarius of the rat.

PubMed

Takemoto, Yumi

2014-07-01

The sulfur-containing excitatory amino acid (EAA) L-cysteine sulfinic acid (CSA), a neurotransmitter candidate, is endogenously synthesized from L-cysteine (Cys). Exogenous Cys administration into the brain produces cardiovascular effects; these effects likely occur via synaptic stimulation of central nervous system (CNS) neurons that regulate peripheral cardiovascular function. However, the cardiovascular responses produced by CNS Cys administration could result from CSA biosynthesized in synapse. The present study examined the role of CSA in Cys-induced cardiovascular responses within the nucleus tractus solitarius (NTS) of anesthetized rats. The NTS receives input from various visceral afferents that gate autonomic reflexes, including cardiovascular reflexes. Within the NTS, both Cys and CSA microinjections produced decrease responses in arterial blood pressure and heart rate that were similar to those produced by L-glutamate. Co-injection of the ionotropic EAA receptor antagonist kynurenic acid abolished Cys-, but not CSA-, induced cardiovascular responses. This finding suggests that only Cys-induced cardiovascular responses are mediated by kynurenate-sensitive receptors. This study provides the first demonstration that Cys- and CSA-induced cardiovascular responses occur via different mechanisms in the NTS of rats. Further, this study also indicates that Cys-induced cardiovascular responses do not occur via CSA. Thus, within the NTS, endogenous Cys and/or CSA might be involved in cardiovascular regulation.

Reliability Assessment and Activation Energy Study of Au and Pd-Coated Cu Wires Post High Temperature Aging in Nanoscale Semiconductor Packaging.

PubMed

Gan, C L; Hashim, U

2013-06-01

Wearout reliability and high temperature storage life (HTSL) activation energy of Au and Pd-coated Cu (PdCu) ball bonds are useful technical information for Cu wire deployment in nanoscale semiconductor device packaging. This paper discusses the influence of wire type on the wearout reliability performance of Au and PdCu wire used in fine pitch BGA package after HTSL stress at various aging temperatures. Failure analysis has been conducted to identify the failure mechanism after HTSL wearout conditions for Au and PdCu ball bonds. Apparent activation energies (Eaa) of both wire types are investigated after HTSL test at 150 °C, 175 °C and 200 °C aging temperatures. Arrhenius plot has been plotted for each ball bond types and the calculated Eaa of PdCu ball bond is 0.85 eV and 1.10 eV for Au ball bond in 110 nm semiconductor device. Obviously Au ball bond is identified with faster IMC formation rate with IMC Kirkendall voiding while PdCu wire exhibits equivalent wearout and or better wearout reliability margin compare to conventional Au wirebond. Lognormal plots have been established and its mean to failure (t 50 ) have been discussed in this paper.

Relation of soya bean meal level to the concentration of plasma free amino acids and body growth in white rats.

PubMed

Mandal, Tapas K; Parvin, Nargish; Mondal, Santanu; Saxena, Vijaylaxmi; Saxena, Ashok K; Sarkar, Sabyasachi; Saha, Mitali

2012-04-01

Amino acid (AA) levels in plasma and body growth were determined in rats (n20) fed diets with different soya bean meal levels. Free AA in plasma was determined by reversed-phase high-pressure liquid chromatography. We have used four levels of protein diets like 8%, 15%, 23% and 35% in this trial. Rats which were fed the low-protein (8%) diet with low percentage of soya bean meal were found to be growth-retarded. The body weight gain of high protein group (35%) was lower than that of the 23% groups. In the rats fed with the low-soya bean meal diet, some nonessential AA (NEAA) in plasma like asparagine, aspartic acid, cysteine, glutamic acid and serine increased, whereas the essential AA (EAA), with the exception of arginine, methionine and valine decreased. Here, plasma EAA-to-NEAA ratios were not correlated to growth and experimental diet. We hypothesize that AA metabolism is associated to changes in growth in rats on different protein intake. This study has showed the sensitivity of body mass gain, feed intake, feed conversion rate of rats to four levels of protein in the diet under controlled experimental conditions. © 2011 Blackwell Verlag GmbH.

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

In vivo protein quality of selected cereal-based staple foods enriched with soybean proteins

PubMed Central

Acevedo-Pacheco, Laura; Serna-Saldívar, Sergio O.

2016-01-01

Background One way to diminish protein malnutrition in children is by enriching cereal-based flours for the manufacturing of maize tortillas, wheat flour tortillas, and yeast-leavened breads, which are widely consumed among low socio-economic groups. Objective The aim was to determine and compare the essential amino acid (EAA) scores, protein digestibility corrected amino acid scores (PDCAAS), and in vivo protein quality (protein digestibility, protein efficiency ratio (PER), biological values (BV), and net protein utilization (NPU) values) of regular versus soybean-fortified maize tortillas, yeast-leavened bread, and wheat flour tortillas. Design To comparatively assess differences in protein quality among maize tortillas, wheat flour tortillas, and yeast-leavened breads, EAA compositions and in vivo studies with weanling rats were performed. The experimental diets based on regular or soybean-fortified food products were compared with a casein-based diet. Food intake, weight gains, PER, dry matter and protein digestibility, BV, NPU, and PDCAAS were assessed. The soybean-fortified tortillas contained 6% of defatted soybean flour, whereas the yeast-leavened bread flour contained 4.5% of soybean concentrate. Results The soybean-fortified tortillas and bread contained higher amounts of lysine and tryptophan, which improved their EAA scores and PDCAAS. Rats fed diets based on soybean-fortified maize or wheat tortillas gained considerably more weight and had better BV and NPU values compared with counterparts fed with respective regular products. As a result, fortified maize tortillas and wheat flour tortillas improved PER from 0.73 to 1.64 and 0.69 to 1.77, respectively. The PER improvement was not as evident in rats fed the enriched yeast-leavened bread because the formulation contained sugar that decreased lysine availability possibly to Maillard reactions. Conclusions The proposed enrichment of cereal-based foods with soybean proteins greatly improved PDCAAS, animal growth, nitrogen retention, and PER primarily in both maize and wheat flour tortillas. Therefore, these foods can help to diminish protein malnutrition among children who greatly depend on cereals as the main protein dietary source. PMID:27765143

Light-Induced Alterations in Striatal Neurochemical Profiles

NASA Technical Reports Server (NTRS)

Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.

1997-01-01

Much of our present knowledge regarding circadian rhythms and biological activity during space flight has been derived from those missions orbiting the Earth. During space missions, astronauts can become exposed to bright/dark cycles that vary considerably from those that entrain the mammalian biological timing system to the 24-hour cycle found on Earth. As a spacecraft orbits the Earth, the duration of the light/dark period experienced becomes a function of the time it takes to circumnavigate the planet which in turn depends upon the altitude of the craft. Orbiting the Earth at an altitude of 200-800 km provides a light/dark cycle lasting between 80 and 140 minutes, whereas a voyage to the moon or even another planet would provide a light condition of constant light. Currently, little is known regarding the effects of altered light/dark cycles on neurochemical levels within the central nervous system (CNS). Many biochemical, physiological and behavioral phenomena are under circadian control, governed primarily by the hypothalamic suprachiasmatic nucleus. As such, these phenomena are subject to influence by the environmental light/dark cycle. Circadian variations in locomotor and behavioral activities have been correlated to both the environmental light/dark cycle and to dopamine (DA) levels within the CNS. It has been postulated by Martin-Iverson et al. that DA's role in the control of motor activity is subject to modulation by circadian rhythms (CR), environmental lighting and excitatory amino acids (EAAs). In addition, DA and EAA receptor regulated pathways are involved in both the photic entrainment of CR and the control of motor activity. The cellular mechanisms by which DA and EAA-receptor ligands execute these functions, is still unclear. In order to help elucidate these mechanisms, we set out to determine the effects of altered environmental light/dark cycles on CNS neurotransmitter levels. In this study, we focused on the striatum, a region of the brain that receives a number of dopaminergic and glutamatergic input and is known to be involved in the modulation of locomotor and behavioral responses.

Effects of high peanut meal with different crude protein level supplemented with amino acids on performance, carcass traits and nitrogen retention of Chinese Yellow broilers.

PubMed

Gou, Z Y; Jiang, S Q; Jiang, Z Y; Zheng, C T; Li, L; Ruan, D; Chen, F; Lin, X J

2016-08-01

This study assessed the effects of feeding high peanut meal diets of reduced crude protein (CP) content supplemented with essential amino acids (EAA) on growth performance, carcass traits, biochemical indices in plasma, and nitrogen (N) retention of male and female Lingnan Yellow broilers from day 22 to day 42 of age. Each of four dietary treatments (19%, 18%, 17% or 16% CP, dietary CP level reduced by the reduced dietary peanut meal) contained six replicate pens with 35 birds of each sex (males and females with equal number), separately (1680 in total). The three diets with reduced CP were supplemented with 5 EAA to meet the requirements and provide the same levels as in the 19% CP diet. Average daily gain decreased and feed:gain ratio was worse in both sexes with reduced CP% (linear, p < 0.05). Dressing percentage increased as CP% decreased in males (linear, p < 0.05) and thigh muscle percentage reduced slightly in females (linear, p < 0.05). Abdominal fat percentage of males fed the 17% CP was the lowest (quadratic, p < 0.05). The plasma metabolic indices, concentrations of triglycerides and malondialdehyde, showed linear responses to reduced CP% (p < 0.05) with triglycerides increasing while malondialdehyde decreased. Plasma uric acid increased in females (linear, p < 0.05), but not in males, as CP% decreased. Efficiency of N retention increased and N excretion strikingly decreased with lower CP diets (p < 0.001), and both variables showed significant (p < 0.05) linear and quadratic effects. It is concluded that there was a limit to which dietary CP of broilers could be reduced without adverse effects. Dietary CP could be reduced to 17% for males and 18% for females (or 18% when fed together) between day 22 and day 42, if diets are supplemented with synthetic EAA. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

75 FR 67947 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... DEPARTMENT OF COMMERCE Submission for OMB Review; Comment Request The Department of Commerce will... Secretary of Commerce to issue regulations to implement the EAA including those provisions authorizing the... Obligation: Required to obtain benefits. OMB Desk Officer: Jasmeet Seehra, (202) 395-3123. Copies of the...

Effect of early antibiotic administration on cecal bacterial communities and their metabolic profiles in pigs fed diets with different protein levels.

PubMed

Zhang, Chuanjian; Yu, Miao; Yang, Yuxiang; Mu, Chunlong; Su, Yong; Zhu, Weiyun

2016-12-01

This study investigated the effects of early antibiotic administration (EAA) on cecal bacterial communities and their metabolic profiles in pigs fed diets with different protein levels. Eighteen litters (total 180) of piglets on day (d) 7 were fed either a commercial creep feed or commercial creep feed + antibiotic (Olaquindox, Oxytetracycline Calcium and Kitasamycin) until d 42. On d 42, pigs within each group were further randomly fed a normal crude protein (CP) diet (20% and 18% CP from d 42 to d 77 and d 77 to d 120, respectively) or a low-CP diet (16% and 14% CP from d 42 to d 77 and d 77 to d 120, respectively), generating 4 groups, control-low CP (Con-LP), control-normal CP (Con-NP), antibiotic-low CP (Ant-LP) and antibiotic-normal CP (Ant-NP), respectively. On d 77 and d 120, 5 pigs per group were slaughtered and cecal materials were collected for bacterial analysis. With cecal bacteria, principle component analysis (PCA) of the denaturing gradient gel electrophoresis (DGGE) profile showed two distinct groups of samples from low-CP diet and samples from normal-CP diet. Real-time PCR showed that EAA did not have significant effect on major bacterial groups, only showed significant interactions (P < 0.05) with CP level for Lactobacillus counts on d 77 and Clostridium cluster XIVa counts on d 120 with higher values in the Con-NP group compared to the Ant-NP groups. Low-CP diet increased (P < 0.05) short-chain fatty acids (SCFA) producing bacteria counts (Bacteroidetes on d 77 and d 120; Clostridium cluster IV and Clostridium cluster XIVa on d 77), but decreased (P < 0.05) Escherichia coli counts on d 77 and d 120. For metabolites, EAA increased (P < 0.05) protein fermentation products (p-cresol, indole and skatole on d 77; ammonia, putrescine and spermidine on d 120), and showed significant interactions (P < 0.05) with CP level for p-cresol and skatole concentrations on d 77 and putrescine and spermidine concentrations on d 120 with higher values in the Ant-LP group compared to the Con-LP groups. Low-CP diet increased (P < 0.05) SCFA concentration (propionate and butyrate) on d 77, but reduced (P < 0.05) the protein fermentation products (ammonia, phenol and indole on d 77; branched chain fatty acid (BCFA), ammonia, tyramine, cadaverine and indole on d 120). These results indicate that EAA had less effect on bacterial communities, but increased bacterial fermentation of protein in the cecum under low-CP diet. Low-CP diet altered bacterial communities with an increase in the counts of SCFA-producing bacteria and a decrease in the counts of Escherichia coli, and markedly reduced the protein fermentation products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of supplementation with amino acids or their metabolites on muscle wasting in patients with critical illness or other muscle wasting illness: a systematic review.

PubMed

Wandrag, L; Brett, S J; Frost, G; Hickson, M

2015-08-01

Muscle wasting during critical illness impairs recovery. Dietary strategies to minimise wasting include nutritional supplements, particularly essential amino acids. We reviewed the evidence on enteral supplementation with amino acids or their metabolites in the critically ill and in muscle wasting illness with similarities to critical illness, aiming to assess whether this intervention could limit muscle wasting in vulnerable patient groups. Citation databases, including MEDLINE, Web of Knowledge, EMBASE, the meta-register of controlled trials and the Cochrane Collaboration library, were searched for articles from 1950 to 2013. Search terms included 'critical illness', 'muscle wasting', 'amino acid supplementation', 'chronic obstructive pulmonary disease', 'chronic heart failure', 'sarcopenia' and 'disuse atrophy'. Reviews, observational studies, sport nutrition, intravenous supplementation and studies in children were excluded. One hundred and eighty studies were assessed for eligibility and 158 were excluded. Twenty-two studies were graded according to standardised criteria using the GRADE methodology: four in critical care populations, and 18 from other clinically relevant areas. Methodologies, interventions and outcome measures used were highly heterogeneous and meta-analysis was not appropriate. Methodology and quality of studies were too varied to draw any firm conclusion. Dietary manipulation with leucine enriched essential amino acids (EAA), β-hydroxy-β-methylbutyrate and creatine warrant further investigation in critical care; EAA has demonstrated improvements in body composition and nutritional status in other groups with muscle wasting illness. High-quality research is required in critical care before treatment recommendations can be made. © 2014 The British Dietetic Association Ltd.

15 CFR 764.3 - Sanctions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... to the Secretary of Defense, except in the case of an individual, shall be fined not more than five... licenses (See section 11B of the EAA, Missile Proliferation Violations, and the Iran-Iraq Arms Non... Department of State may deny licenses or approvals for the export or reexport of defense articles and defense...

15 CFR 764.3 - Sanctions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... MEASURES § 764.3 Sanctions. (a) Administrative. Violations of the EAA, the EAR, or any order, license or... violation, and in the event that any provision of the EAR is continued by IEEPA or any other authority, the... engage in export and reexport transactions involving items subject to the EAR, or that restricts access...

15 CFR 764.3 - Sanctions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... MEASURES § 764.3 Sanctions. (a) Administrative. Violations of the EAA, the EAR, or any order, license or... each violation, and in the event that any provision of the EAR is continued by IEEPA or any other... persons to engage in export and reexport transactions involving items subject to the EAR, or that...

15 CFR 764.3 - Sanctions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... MEASURES § 764.3 Sanctions. (a) Administrative. Violations of the EAA, the EAR, or any order, license or... violation, and in the event that any provision of the EAR is continued by IEEPA or any other authority, the... engage in export and reexport transactions involving items subject to the EAR, or that restricts access...

15 CFR 764.3 - Sanctions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... MEASURES § 764.3 Sanctions. (a) Administrative. Violations of the EAA, the EAR, or any order, license or... violation, and in the event that any provision of the EAR is continued by IEEPA or any other authority, the... engage in export and reexport transactions involving items subject to the EAR, or that restricts access...

Lysine supplementation of commercial fishmeal-free diet in hybrid striped bass affect growth expression genes

USDA-ARS?s Scientific Manuscript database

Substitution of fishmeal with alternate proteins in aquafeeds often results in dietary imbalances of first-limiting essential amino acids (EAA) and poorer fish performance. Previously, we conducted a growth trial to test the hypothesis that ideal protein theory accurately predicts first-limiting ami...

Lysine optimization of a commercial fishmeal-free diet for hybrid striped bass (Morone chrysops x M. saxatilis)

USDA-ARS?s Scientific Manuscript database

Substitution of fishmeal with alternate proteins in aquafeeds often results in dietary imbalances of firstlimiting essential amino acids (EAA) and poorer fish performance. This growth trial was undertaken to test the hypothesis that ideal protein theory accurately predicts first-limiting amino acids...

Carbon balance of sugarcane agriculture on histosols of the everglades agricultural area: review, analysis, and global energy perspectives

USDA-ARS?s Scientific Manuscript database

Biofuels production from crop products and cellulosic by-products, including sugarcane, has received much attention. In Florida, most sugarcane is produced on drained Histosols (organic soils) of the Everglades Agricultural Area (EAA). Subsidence has occurred via microbial oxidation since drainage i...

The new system of review by multicentre research ethics committees: prospective study

PubMed Central

Tully, Joanna; Ninis, Nelly; Booy, Robert; Viner, Russell

2000-01-01

Objective To assess the function of the new system of review by multicentre research ethics committees and to highlight areas where improvement is still needed. Design Prospectively collected data from a multicentre study was examined with respect to the ethics review process. Administrative, financial, and time elements of the review process were audited. Setting A single multicentre research ethics committee and 125 local ethics committees from six regions of England. Main outcome measures Time to reply, time to approval, and number of non-local changes to the application requested. Results Only 40% of local ethics committees considered our study in the manner specified in the 1998 directive. Less than a third of committees replied within the 21 day period stipulated, although committees acting by executive subcommittee replied more quickly than those not acting by executive subcommittee. There was a tendency for executive subcommittees to approve studies in a shorter time. Local ethics committees asked for a large number of non-local changes to the application. The financial cost of applying to multiple ethics committees remains high, mainly because multiple copies of research applications are being requested. Conclusions The new system of approval by multicentre research ethics committee for multicentre studies was introduced to reduce administrative costs, speed up the process of reviews by multiple research ethics committees, and standardise the conclusions of the local research ethics committees. Since its introduction an improvement has been seen, but the system is not yet universally functioning as intended. Ethics review still remains a hindrance to the financial resources and commencement of national studies. We strongly support the structure of review by multicentre research ethics committees but suggest that the system has yet to achieve its aims. PMID:10784541

Characterization of Edible Pork By-products by Means of Yield and Nutritional Composition

PubMed Central

Moon, Sung Sil

2014-01-01

Basic information regarding the yield and nutritional composition of edible pork by-products, namely heart, liver, lung, stomach, spleen, uterus, pancreas, and small and large intestines, was studied. Our results revealed that the yields varied widely among the pork by-products examined; in particular, liver had the highest yield (1.35%); whereas, spleen had the lowest yield (0.16%). The approximate composition range (minimum to maximum) of these by-products was found to be: moisture 71.59-82.48%; fat 0.28-19.54%; ash 0.155-1.34%, and protein 8.45-22.05%. The highest protein, vitamin A, B2, B6, and total essential amino acid (EAA) contents were found in liver. Large intestine had the highest fat content and lowest EAA content. Heart had the highest vitamin B1 content, whereas pancreas had the highest niacin and vitamin B3 contents. The concentrations of Fe and Zn were highest in liver and pancreas. Total saturated fatty acids (SFA) levels and polyunsaturated fatty acids (PUFA) levels between the by-products ranged from 43.15-50.48%, and 14.92-30.16%, respectively. Furthermore, with the exception of large intestine, all the by-products showed favorable PUFA/SFA ratios. The study indicated that almost all of the pork by-products examined were good sources of important nutrients, and that these data will be of great importance in the promotion of the consumption of edible pork by-products, as well as their utilization in meat processing. PMID:26761170

15 CFR Supplement No. 1 to Part 764 - Standard Terms of Orders Denying Export Privileges

Code of Federal Regulations, 2010 CFR

2010-01-01

... decision following charges of violation, settlement agreement, section 11(h) of the EAA, or temporary... denial order; (2) the basis for the denial order, such as final decision following charges of violation..., transporting, financing, or otherwise servicing in any way, any transaction involving any item exported or to...

15 CFR 766.25 - Administrative action denying export privileges.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of a violation of the EAA, the EAR, or any order, license, or authorization issued thereunder; any... transaction subject to the EAR. Before taking action to deny a person export privileges under this section... privileges” for purposes of § 736.2(b)(4) (General Prohibition 4—Engage in actions prohibited by a denial...

15 CFR 766.24 - Temporary denials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... temporary denial orders were issued. Without limiting any other action BIS may take under the EAR with..., as defined in this section, of the EAA, the EAR, or any order, license or authorization issued... provided for in § 764.3(a)(2) of the EAR. (b) Issuance. (1) The Assistant Secretary may issue an order...

15 CFR 766.25 - Administrative action denying export privileges.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of a violation of the EAA, the EAR, or any order, license, or authorization issued thereunder; any... transaction subject to the EAR. Before taking action to deny a person export privileges under this section... privileges” for purposes of § 736.2(b)(4) (General Prohibition 4—Engage in actions prohibited by a denial...

15 CFR 766.24 - Temporary denials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... temporary denial orders were issued. Without limiting any other action BIS may take under the EAR with..., as defined in this section, of the EAA, the EAR, or any order, license or authorization issued... provided for in § 764.3(a)(2) of the EAR. (b) Issuance. (1) The Assistant Secretary may issue an order...

15 CFR 766.24 - Temporary denials.

Code of Federal Regulations, 2014 CFR

2014-01-01

... temporary denial orders were issued. Without limiting any other action BIS may take under the EAR with..., as defined in this section, of the EAA, the EAR, or any order, license or authorization issued... provided for in § 764.3(a)(2) of the EAR. (b) Issuance. (1) The Assistant Secretary may issue an order...

15 CFR 766.25 - Administrative action denying export privileges.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of a violation of the EAA, the EAR, or any order, license, or authorization issued thereunder; any... transaction subject to the EAR. Before taking action to deny a person export privileges under this section... privileges” for purposes of § 736.2(b)(4) (General Prohibition 4—Engage in actions prohibited by a denial...

15 CFR 766.25 - Administrative action denying export privileges.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of a violation of the EAA, the EAR, or any order, license, or authorization issued thereunder; any... transaction subject to the EAR. Before taking action to deny a person export privileges under this section... privileges” for purposes of § 736.2(b)(4) (General Prohibition 4—Engage in actions prohibited by a denial...

15 CFR 766.24 - Temporary denials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... temporary denial orders were issued. Without limiting any other action BIS may take under the EAR with..., as defined in this section, of the EAA, the EAR, or any order, license or authorization issued... provided for in § 764.3(a)(2) of the EAR. (b) Issuance. (1) The Assistant Secretary may issue an order...

15 CFR 766.25 - Administrative action denying export privileges.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of a violation of the EAA, the EAR, or any order, license, or authorization issued thereunder; any... transaction subject to the EAR. Before taking action to deny a person export privileges under this section... privileges” for purposes of § 736.2(b)(4) (General Prohibition 4—Engage in actions prohibited by a denial...

15 CFR 766.24 - Temporary denials.

Code of Federal Regulations, 2010 CFR

2010-01-01

... temporary denial orders were issued. Without limiting any other action BIS may take under the EAR with..., as defined in this section, of the EAA, the EAR, or any order, license or authorization issued... provided for in § 764.3(a)(2) of the EAR. (b) Issuance. (1) The Assistant Secretary may issue an order...

Lysine optimization of a commercial fishmeal-free diet for hybrid striped bass (Morone chrysops x M. saxatilis)

USDA-ARS?s Scientific Manuscript database

Substitution of fishmeal with alternate proteins in aquafeeds often results in dietary imbalances of first-limiting essential amino acids (EAA) and poorer fish performance. This 12-week growth trial was undertaken to test the hypothesis that ideal protein theory accurately predicts first-limiting am...

Toward the Development of Aluminum Cluster-Containing Materials for Propulsion Applications

DTIC Science & Technology

2011-02-22

our main example. Photoelectron spectroscopy revealed that Al13H - has two isomers and for both provided vertical detachment energies ( VDE ) for their...The relative energies for both isomers in their anionic and their neutral charge states as well as EAa and VDE values for both isomers were also

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS).

PubMed

Cruz-Jentoft, Alfonso J; Landi, Francesco; Schneider, Stéphane M; Zúñiga, Clemente; Arai, Hidenori; Boirie, Yves; Chen, Liang-Kung; Fielding, Roger A; Martin, Finbarr C; Michel, Jean-Pierre; Sieber, Cornel; Stout, Jeffrey R; Studenski, Stephanie A; Vellas, Bruno; Woo, Jean; Zamboni, Mauro; Cederholm, Tommy

2014-11-01

to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

PubMed Central

Cruz-Jentoft, Alfonso J.; Landi, Francesco; Schneider, Stéphane M.; Zúñiga, Clemente; Arai, Hidenori; Boirie, Yves; Chen, Liang-Kung; Fielding, Roger A.; Martin, Finbarr C.; Michel, Jean-Pierre; Sieber, Cornel; Stout, Jeffrey R.; Studenski, Stephanie A.; Vellas, Bruno; Woo, Jean; Zamboni, Mauro; Cederholm, Tommy

2014-01-01

Objective: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Methods: PubMed and Dialog databases were searched (January 2000–October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected. Results: prevalence of sarcopenia was, with regional and age-related variations, 1–29% in community-dwelling populations, 14–33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function. Conclusion: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes. PMID:25241753

DOE Office of Scientific and Technical Information (OSTI.GOV)

Capece, John; Hanlon, Ed A.

The public purchase of farmlands in the EAA provides an opportunity for transforming farming systems into truly sustainable systems and these can support the Everglades restoration efforts. The concept proposed in this presentation is that by reducing the yield intensity of farms and adding ecosystem services, public farm lands can serve both restoration and the economy more effectively and more efficiently. This working hypothesis will be evaluated by applying systems analysis approaches including life cycle analysis and embodied energy analysis. The rationale for pursuing new approaches ranges from the fact that climate change threats are global, not local, to themore » fact that eliminating Florida farms and moving production elsewhere yields no net ecological benefit. Historic water flow from Lake Okeechobee to Everglades is shown and the current concept of moving water explained. Southern Flow Way Plan 6 is explained and sustainable farming system in this newly acquired land presented. To determine if an EAA pulse-way strategy would work and meet the sustainability criteria requires integrated analysis of several systems - water budget, soil & water nutrient dynamics, prospects for new sugarcane varieties, soil subsidence and overall energy and carbon budget.« less

Acute regulation of IGF-I by alterations in post-exercise macronutrients.

PubMed

Foster, E B; Fisher, G; Sartin, J L; Elsasser, T H; Wu, G; Cowan, W; Pascoe, D D

2012-04-01

This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise nutritional protocols: (1) placebo (EX); (2) carbohydrate only (CHO); and (3) essential amino acid/carbohydrate (EAA/CHO). Samples were analyzed for growth hormone (GH), free IGF-I, IGFBP-1, IGFBP-2, insulin, hematocrit, hemoglobin, serum leucine, matrix metalloproteinase-9 (MMP-9) proteolytic activity, and presence of IGFBP-3 protease activity. No evidence for IGFBP-3 proteolysis was observed. Significant increases in [free IGF-I] and [leucine] were observed in the EAA/CHO group only. Significant differences were noted in [IGFBP-1] and [IGFBP-2] across conditions. Significant increases in [GH] and MMP-9 activity were observed in all groups. These results indicate that post-exercise macronutrient ratio is a determinant of [free IGF-I], [IGFBP-1 and -2] and may play a role in modulating the IGF-I axis in vivo.

Neuroprotective effects of ebselen following forebrain ischemia: involvement of glutamate and nitric oxide.

PubMed

Koizumi, Hiroyasu; Fujisawa, Hirosuke; Suehiro, Eiichi; Shirao, Satoshi; Suzuki, Michiyasu

2011-01-01

Ebselen is a mimic of glutathione peroxidase that reacts with peroxynitrite and inhibits nitric oxide (NO) synthase. Ebselen has beneficial effects on the neurological outcome of patients with stroke. In this study, the mechanisms by which ebselen can elicit neuroprotective effects against ischemic brain injury were investigated in male Wistar rats. Experimental forebrain ischemia was induced by bilateral common carotid artery occlusion with hemorrhagic hypotension. Ebselen was administered to animals in the treatment group 2 hours prior to the induction of forebrain ischemia, and placebo was administered in the control group. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. Cortical extracellular levels of excitatory amino acids (EAAs) and NO were evaluated using in vivo microdialysis. Neuronal damage in the CA1 subfield of the hippocampus was assessed in brains harvested after a 24-hour period of survival. CBF did not recover to normal physiological levels after ischemic insults in either the control or treatment groups. The differences in the sequential changes in extracellular EAA and NO levels between groups were not statistically significant. There was a significantly larger mean density of intact, undamaged neurons in the CA1 subfield in the treatment group than in the control group. The neuroprotective effects of ebselen were reflected in the histological findings, without significant inhibition of glutamate release or NO synthesis during the acute phase of experimentally induced cerebral ischemia.

Proximate composition, amino acid and fatty acid profiles of marine snail Rapana venosa meat, visceral mass and operculum.

PubMed

Luo, Fenglei; Xing, Ronge; Wang, Xueqin; Peng, Quancai; Li, Pengcheng

2017-12-01

Rapana venosa (Rv), an important marine snail, demonstrates an increasing nutritional and economic importance. However, there is still limited information available on their nutritional composition. The present study highlights and provides new information on the proximate composition, amino acid and fatty acid profiles of different body parts of Rv, aiming for its better application and research. The operculum contained a high amount of protein and flavor amino acids. The edible tissues, including meat and visceral mass, were valuable sources of essential amino acids (EAA) apart from methionine and cysteine. In addition, the meat contained high amount of taurine. Fatty acid analysis indicated that the edible tissues contained high amounts of ω3 fatty acids, especially eicosapentaenoic acid (EPA) (C20:5ω3) and docosahexaenoic acid (DHA) (C22:6ω3), and had a low ω6/ω3 fatty acid ratio. Interestingly, significantly higher concentrations of most nutritional elements such as fat, EAA, EPA and DHA, were found in the visceral mass compared to those in the meat. The operculum of Rv may became a very interesting source for some protein and flavor peptide development, and the edible parts of Rv may be utilized for special dietary applications requiring high amounts of taurine, EPA, DHA and a lower ω6/ω3 fatty acid ratio. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Central phencyclidine (PCP) receptor binding is glutamate dependent: evidence for a PCP/excitatory amino acid receptor (EAAR) complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loo, P.; Braunwalder, A.; Lehmann, J.

PCP and other dissociative anesthetica block the increase in neuronal firing rate evoked by the EAAR agonist, N-methyl-Daspartate. NMDA and other EAAs such as glutamate (glu) have not been previously shown to affect PCP ligand binding. In the present study, using once washed rat forebrain membranes, 10 ..mu..M-glu was found to increase the binding of (/sup 3/H)TCP, a PCP analog, to defined PCP recognition sites by 20%. Removal of glu and aspartate (asp) by extensive washing decreased TCP binding by 75-90%. In these membranes, 10 ..mu..M L-glu increased TCP binding 3-fold. This effect was stereospecific and evoked by other EAAsmore » with the order of activity, L-glu > D-asp > L- asp > NMDA > D-glu > quisqualate. Kainate, GABA, NE, DA, 5-HT, 2-chloroadenosine, oxotremorine and histamine had no effect on TCP binding at concentrations up to 100 ..mu..M. The effects of L-glu were attenuated by the NMDA-type receptor antagonist, 2-amino-7--phosphonoheptanoate (AP7; 10 ..mu..M-1 mM). These findings indicate that EAAS facilitate TCP binding, possibly through NMDA-type receptors. The observed interaction between the PCP receptor and EAARs may reflect the existence of a macromolecular receptor complex similar to that demonstrated for the benzodiazepines and GABA.« less

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

PubMed

Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob; Barrows, Katherine M; Briggs, Robert A; Kwon, Oh Sung; Young, Laura M; Hopkins, Paul N; Volpi, Elena; Marcus, Robin L; LaStayo, Paul C; Drummond, Micah J

2015-09-15

Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials.

PubMed

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials.

[Relevance of the sentinel lymph node biopsy in breast multifocal and multicentric cancer].

PubMed

Mosbah, R; Raimond, E; Pelissier, A; Hocedez, C; Graesslin, O

2015-05-01

The sentinel lymph node biopsy is a gold standard in the management of breast cancer. Its role in multifocal or multicentric tumors is still evolving. The aim of this study is to assess the feasibility and pertinence of sentinel lymph node biopsy in multifocal and multicentric tumors based on a systematic review of literature. A systematic review was conducted searching in the following electronic databases PubMed using "sentinel lymph node biopsy", "breast cancer", "multifocal tumor", "multicentric tumor" and "multiple tumor" as keywords. We included original articles published between 2000 and 2014, both French and English, studying feasibility of sentinel lymph node biopsy in invasive breast cancer, multicentric and/or multifocal tumors. The first end point was success rate and false negative rate. Twenty-six articles were included in this literature review, with 2212 cases (782 multifocal, 737 multicentric and 693 multiple tumors). Percentage of tumors whose stage was higher than stage T2 ranged from 0 to 86.3%. Success rate average was 83.1%. False negative average was 8.2%. False negative rate was less than 10% in 15 articles. Mean of sentinel lymph node biopsy was 2 (1-9). The average rate of sentinel lymph node positive was 50.6%. Axillary recurrence rate was 0.5%. Despite the methodological biases of the studies included in this review of literature, the false negative rate of sentinel node biopsy in multifocal and multicentric breast cancers are less than 10% with a low rate of axillary recurrence. Despite the lack of randomized study, this procedure can be routinely performed in accordance with rigorous technical process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Effects of Dietary Crude Protein Levels and Cysteamine Supplementation on Protein Synthetic and Degradative Signaling in Skeletal Muscle of Finishing Pigs.

PubMed

Zhou, Ping; Zhang, Lin; Li, Jiaolong; Luo, Yiqiu; Zhang, Bolin; Xing, Shen; Zhu, Yuping; Sun, Hui; Gao, Feng; Zhou, Guanghong

2015-01-01

Dietary protein levels and cysteamine (CS) supplementation can affect growth performance and protein metabolism of pigs. However, the influence of dietary protein intake on the growth response of CS-treated pigs is unclear, and the mechanisms involved in protein metabolism remain unknown. Hence, we investigated the interactions between dietary protein levels and CS supplementation and the effects of dietary crude protein levels and CS supplementation on protein synthetic and degradative signaling in skeletal muscle of finishing pigs. One hundred twenty barrows (65.84 ± 0.61 kg) were allocated to a 2 × 2 factorial arrangement with five replicates of six pigs each. The primary variations were dietary crude protein (CP) levels (14% or 10%) and CS supplemental levels (0 or 700 mg/kg). The low-protein (LP) diets (10% CP) were supplemented with enough essential amino acids (EAA) to meet the NRC AA requirements of pigs and maintain the balanced supply of eight EAA including lysine, methionine, threonine, tryptophan, valine, phenylalanine, isoleucine, and leucine. After 41 days, 10 pigs per treatment were slaughtered. We found that LP diets supplemented with EAA resulted in decreased concentrations of plasma somatostatin (SS) (P<0.01) and plasma urea nitrogen (PUN) (P<0.001), while dietary protein levels did not affect other traits. However, CS supplementation increased the average daily gain (P<0.001) and lean percentage (P<0.05), and decreased the feed conversion ratio (P<0.05) and back fat (P<0.05). CS supplementation also increased the concentrations of plasma insulin-like growth factor 1 (IGF-1) (P<0.001), and reduced the concentrations of leptin, SS, and PUN (P<0.001). Increased mRNA abundance of Akt1 and IGF-1 signaling (P<0.001) and decreased mRNA abundance of Forkhead Box O (FOXO) 4 (P<0.01) and muscle atrophy F-box (P<0.001) were observed in pigs receiving CS. Additionally, CS supplementation increased the protein levels for the phosphorylated mammalian target of rapamycin (mTOR), eIF-4E binding protein 1, and ribosomal protein S6 kinase 1 (P<0.001). There were no interactions between dietary protein levels and CS supplementation for all traits. In conclusion, dietary protein levels and CS supplementation influenced growth and protein metabolism through independent mechanisms in pigs. In addition, LP diets supplemented with EAA did not affect growth performance and other traits except the concentrations of SS and PUN probably through maintenance of protein synthesis and degradation signaling. Moreover, CS supplementation improved growth performance by increasing plasma IGF-1 concentrations possibly through alterations of mTOR and Akt/FOXO signaling pathways in skeletal muscle of finishing pigs.

Impact of amino acid and CP restriction from 20 to 140 kg BW on performance and dynamics in empty body protein and lipid deposition of entire male, castrated and female pigs.

PubMed

Ruiz-Ascacibar, I; Stoll, P; Kreuzer, M; Boillat, V; Spring, P; Bee, G

2017-03-01

Breeding leaner pigs during the last decades may have changed pig's empty body (EB) composition, a key trait for elaborating feeding recommendations. This research aimed to provide new experimental data on changes in the chemical composition of the EB of pigs from 20 to 140 kg BW. In addition, the impact of a reduction in the dietary CP associated with lower lysine, methionine+cystine, threonine and tryptophan levels was determined. In total, 48 males, castrates and females weighing 20 kg BW were allocated either to a control grower-finisher diet formulated according to current Swiss feeding recommendations, or a low CP grower-finisher diet (80% of control). Feed intake was monitored and pigs were weighed weekly. The chemical composition of EB (blood, hairs and hoofs, offals, bile, carcass) was determined at 20, 40, 60, 80, 100, 120 and 140 kg BW on four pigs per gender and diet (eight pigs per gender at 20 kg). The five fractions were weighed and samples were analysed for dry matter, protein, fat and energy. Nutrient deposition rates and N efficiency were calculated by using the 20 kg BW category as reference. Analysis revealed an accurate feed optimisation for the aforementioned essential amino acids (EAA), whereas digestible isoleucine content in the low CP diet was at 70% of the control diet. Despite similar feed intake, daily gain and feed efficiency were impaired (P<0.01) from 20 to 100 kg BW in the low CP compared with the control pigs. In the same growth period, castrates had the greatest feed intake but, together with females, displayed the lowest (P<0.01) feed efficiency. Protein deposition was reduced (P<0.01) by up to 31% with low CP diet and was lower (P<0.01) in castrates and females than males at 100 kg BW. The greatest fat deposition rates were found with low CP diet and castrates. N efficiency improved (P<0.05) by 10% with the low CP diet from 100 to 140 kg. The males displayed the greatest (P<0.05) N efficiency. These findings suggest that the CP content of finisher II diets could be reduced to 102, 102 and 104 g/kg for females, castrates and males, respectively, without a negative impact on protein deposition or growth. It remains unclear whether the negative effects found in the BW range from 20 to 100 kg on the EB deposition were due to the 20% reduction of the dietary CP and the five limiting EAA or to other EAA via an unbalanced EAA profile.

Conducting a multicentre and multinational qualitative study on patient transitions.

PubMed

Johnson, Julie K; Barach, Paul; Vernooij-Dassen, Myrra

2012-12-01

A multicentre, multinational research study requires careful planning and coordination to accomplish the aims of the study and to ensure systematic and rigorous examination of all project methods and data collected. The aim of this paper is to describe the approach we used during the HANDOVER Project to develop a multicentre, multinational research project for studying transitions of patient care while creating a community of practice for the researchers. We highlight the process used to assure the quality of a multicentre qualitative study and to create a codebook for data analysis as examples of attending to the community of practice while conducting rigorous qualitative research. Essential elements for the success of this multinational, multilanguage research project included recruiting a strong research team, explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalise upon those differences. Although not commonly discussed in reports of large research projects, there is an underlying, concurrent stream of activities to develop a cohesive team that trusts and respects one another's skills and that engage independent researchers in a group process that contributes to achieving study goals. We discuss other lessons learned and offer recommendations for other teams planning multicentre research.

The weed Sorghum almum is a putative alternative host of sugarcane infecting viruses in Florida

USDA-ARS?s Scientific Manuscript database

Sorghum almum or Columbus grass is a common weed growing in the Everglades Agricultural Area (EAA). In recent surveys for alternative hosts of sugarcane yellow leaf virus (SCYLV), 123 out of 141 (87%) plants of S. almum tested positive for this virus by tissue blot immunoassay (TBIA) using polyclona...

Modafinil: A Molecule of Military Interest

DTIC Science & Technology

2001-06-01

noradrenalin LC: locus coeruleus iR-Glu: ionotropic MCn: magnocellular nucleus glutamate receptors (NMDA and non-NMDA) DR: dorsal raphe mR-Glu: metabotropic ...21 This metabotropic receptor agonist. However, the EAA- inhibition of cortical GABA outflow is antagonized release inhibitor propentofylline has...NMDA receptor antagonist and metabotropic psychostimulant, during a sixty-hour sleep receptor agonist. deprivation experiment. Fundam Clin Pharmacol

Export bill and scientific exchanges

NASA Astrophysics Data System (ADS)

President Ronald Reagan has signed into law the reauthorization of the Export Administration Act (EAA), first passed in 1979. The amended version of the law, signed July 12, includes a policy statement in support of “vigorous scientific enterprise. . .in accordance with applicable provisions of law. . .by means of publication, teaching, conferences, and other forms of scholarly exchange.”

Earth Observations taken by the Expedition Seven crew

NASA Image and Video Library

2003-06-19

ISS007-E-07652 (July 2003) --- Part of Oshkosh, Wisconsin, site of a very popular air show, held around this time of year, was photographed by a crew member aboard the International Space Station during its seventh habitation mission. The airfield near Lake Winnebago hosts the mid-summer fly-in event sponsored by the Experimental Aircraft Association (EAA).

Earth Observations taken by the Expedition Seven crew

NASA Image and Video Library

2003-06-19

ISS007-E-07650 (July 2003) --- Part of Oshkosh, Wisconsin, site of a very popular air show, held around this time of year, was photographed by a crew member aboard the International Space Station during its seventh habitation mission. The airfield near Lake Winnebago hosts the mid-summer fly-in event sponsored by the Experimental Aircraft Association (EAA).

Conducting a paediatric multi-centre RCT with an industry partner: challenges and lessons learned.

PubMed

Maskell, Jessica; Newcombe, Peter; Martin, Graham; Kimble, Roy

2012-11-01

There are many benefits of multi-centred research including large sample sizes, statistical power, timely recruitment and generalisability of results. However, there are numerous considerations when planning and implementing a multi-centred study. This article reviews the challenges and successes of planning and implementing a multi-centred prospective randomised control trial involving an industry partner. The research investigated the impact on psychosocial functioning of a cosmetic camouflage product for children and adolescents with burn scarring. Multi-centred studies commonly have many stakeholders. Within this study, six Australian and New Zealand paediatric burn units as well as an industry partner were involved. The inclusion of an industry partner added complexities as they brought different priorities and expectations to the research. Further, multifaceted ethical and institutional approval processes needed to be negotiated. The challenges, successes, lessons learned and recommendations from this study regarding Australian and New Zealand ethics and research governance approval processes, collaboration with industry partners and the management of differing expectations will be outlined. Recommendations for future multi-centred research with industry partners include provision of regular written reports for the industry partner; continual monitoring and prompt resolution of concerns; basic research practices education for industry partners; minimisation of industry partner contact with participants; clear roles and responsibilities of all stakeholders and utilisation of single ethical review if available. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Revisiting the Robustness of PET-Based Textural Features in the Context of Multi-Centric Trials

PubMed Central

Bailly, Clément; Bodet-Milin, Caroline; Couespel, Solène; Necib, Hatem; Kraeber-Bodéré, Françoise; Ansquer, Catherine; Carlier, Thomas

2016-01-01

Purpose This study aimed to investigate the variability of textural features (TF) as a function of acquisition and reconstruction parameters within the context of multi-centric trials. Methods The robustness of 15 selected TFs were studied as a function of the number of iterations, the post-filtering level, input data noise, the reconstruction algorithm and the matrix size. A combination of several reconstruction and acquisition settings was devised to mimic multi-centric conditions. We retrospectively studied data from 26 patients enrolled in a diagnostic study that aimed to evaluate the performance of PET/CT 68Ga-DOTANOC in gastro-entero-pancreatic neuroendocrine tumors. Forty-one tumors were extracted and served as the database. The coefficient of variation (COV) or the absolute deviation (for the noise study) was derived and compared statistically with SUVmax and SUVmean results. Results The majority of investigated TFs can be used in a multi-centric context when each parameter is considered individually. The impact of voxel size and noise in the input data were predominant as only 4 TFs presented a high/intermediate robustness against SUV-based metrics (Entropy, Homogeneity, RP and ZP). When combining several reconstruction settings to mimic multi-centric conditions, most of the investigated TFs were robust enough against SUVmax except Correlation, Contrast, LGRE, LGZE and LZLGE. Conclusion Considering previously published results on either reproducibility or sensitivity against delineation approach and our findings, it is feasible to consider Homogeneity, Entropy, Dissimilarity, HGRE, HGZE and ZP as relevant for being used in multi-centric trials. PMID:27467882

Rearing Tenebrio molitor L. (Coleptera: Tenebrionidae) in the "Lunar Palace 1" during a 105-day multi-crew closed integrative BLSS experiment

NASA Astrophysics Data System (ADS)

Li, Leyuan; Xie, Beizhen; Dong, Chen; Hu, Dawei; Wang, Minjuan; Liu, Guanghui; Liu, Hong

2015-11-01

Yellow mealworm (Tenebrio molitor L.) is one of the animal candidates for space bioregenerative life support systems. In this study, T. molitor was involved in a 105-day multi-crew closed integrative BLSS experiment for a tentative rearing study. The results showed that the overall bioconversion rate (ratio of T. molitor gained to the total feed consumed) of T. molitor reared in the closed system was 8.13%, while 78.43% of the feed was excreted as frass. T. molitor reared in the closed system had a good nutritional composition. The eight essential amino acids (EAAs) in T. molitor larvae accounted for 41.30% of its total amino acids, and most EAA contents were higher than the suggested amino acid pattern recommended by the FAO/WHO. T. molitor sample obtained in this work was high in polyunsaturated fatty acids, and low in saturated fatty acids, indicating that the composition of fatty acids was beneficial to human health. In the open environment outside the experimental system, we simultaneously reared three parallel groups of larval T. molitor using the same feeding regime and temperature condition. Compared with T. molitor reared in the open environment, larvae reared in the closed system grew slower. With the course of time t, the growth rate of T. molitor in the open environment was 0.839e0.017t times that of larvae in the closed system. This paper can provide data for future design and improvement of BLSS containing a T. molitor rearing unit.

Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64.

PubMed

Miller, Julie M; Dewey, Marc; Vavere, Andrea L; Rochitte, Carlos E; Niinuma, Hiroyuki; Arbab-Zadeh, Armin; Paul, Narinder; Hoe, John; de Roos, Albert; Yoshioka, Kunihiro; Lemos, Pedro A; Bush, David E; Lardo, Albert C; Texter, John; Brinker, Jeffery; Cox, Christopher; Clouse, Melvin E; Lima, João A C

2009-04-01

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective "CORE-64" trial ("Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors"). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Leucine acts in the brain to suppress food intake but does not function as a physiological signal of low dietary protein

PubMed Central

Laeger, Thomas; Reed, Scott D.; Henagan, Tara M.; Fernandez, Denise H.; Taghavi, Marzieh; Addington, Adele; Münzberg, Heike; Martin, Roy J.; Hutson, Susan M.

2014-01-01

Intracerebroventricular injections of leucine are sufficient to suppress food intake, but it remains unclear whether brain leucine signaling represents a physiological signal of protein balance. We tested whether variations in dietary and circulating levels of leucine, or all three branched-chain amino acids (BCAAs), contribute to the detection of reduced dietary protein. Of the essential amino acids (EAAs) tested, only intracerebroventricular injection of leucine (10 μg) was sufficient to suppress food intake. Isocaloric low- (9% protein energy; LP) or normal- (18% protein energy) protein diets induced a divergence in food intake, with an increased consumption of LP beginning on day 2 and persisting throughout the study (P < 0.05). Circulating BCAA levels were reduced the day after LP diet exposure, but levels subsequently increased and normalized by day 4, despite persistent hyperphagia. Brain BCAA levels as measured by microdialysis on day 2 of diet exposure were reduced in LP rats, but this effect was most prominent postprandially. Despite these diet-induced changes in BCAA levels, reducing dietary leucine or total BCAAs independently from total protein was neither necessary nor sufficient to induce hyperphagia, while chronic infusion of EAAs into the brain of LP rats failed to consistently block LP-induced hyperphagia. Collectively, these data suggest that circulating BCAAs are transiently reduced by dietary protein restriction, but variations in dietary or brain BCAAs alone do not explain the hyperphagia induced by a low-protein diet. PMID:24898843

Physiological and Morphological Effects of High Water Tables on Early Growth of Giant Reed (Arundo donax), Elephant Grass (Pennisetum purpureum), Energycane and Sugarcane (Saccharum spp.)

USDA-ARS?s Scientific Manuscript database

Increasing demand for renewable energy sources has led to interest in high-biomass crops. Species that have been proposed as well-suited for biofuel production in the Everglades Agricultural Area (EAA) of Florida include Giant Reed (Arundo donax), Elephant Grass (Pennisetum purpureum), Energycane (S...

Growth and clinical variables in nitrogen-restricted piglets fed an adjusted essential amino acid mix: Effects using free amino acid-based diets

USDA-ARS?s Scientific Manuscript database

Excess protein intake in early life has been linked to obesity and metabolic syndrome in later life. Yet, protein, and in particular the essential amino acids (EAA), need to be present in adequate quantity to support growth. Using a piglet model restricted in dietary amino acids (AA), our objective...

MSEBAG: a dynamic classifier ensemble generation based on `minimum-sufficient ensemble' and bagging

NASA Astrophysics Data System (ADS)

Chen, Lei; Kamel, Mohamed S.

2016-01-01

In this paper, we propose a dynamic classifier system, MSEBAG, which is characterised by searching for the 'minimum-sufficient ensemble' and bagging at the ensemble level. It adopts an 'over-generation and selection' strategy and aims to achieve a good bias-variance trade-off. In the training phase, MSEBAG first searches for the 'minimum-sufficient ensemble', which maximises the in-sample fitness with the minimal number of base classifiers. Then, starting from the 'minimum-sufficient ensemble', a backward stepwise algorithm is employed to generate a collection of ensembles. The objective is to create a collection of ensembles with a descending fitness on the data, as well as a descending complexity in the structure. MSEBAG dynamically selects the ensembles from the collection for the decision aggregation. The extended adaptive aggregation (EAA) approach, a bagging-style algorithm performed at the ensemble level, is employed for this task. EAA searches for the competent ensembles using a score function, which takes into consideration both the in-sample fitness and the confidence of the statistical inference, and averages the decisions of the selected ensembles to label the test pattern. The experimental results show that the proposed MSEBAG outperforms the benchmarks on average.

Treating KSHV-Associated Multicentric Castleman Disease

Cancer.gov

In this study, patients with KSHV-associated multicentric Castleman disease will receive IV tocilizumab every other week for up to 12 weeks. Patients who do not benefit may go on to receive high-dose AZT and valganciclovir as well.

Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women.

PubMed

Wilkinson, Daniel J; Bukhari, Syed S I; Phillips, Bethan E; Limb, Marie C; Cegielski, Jessica; Brook, Matthew S; Rankin, Debbie; Mitchell, William K; Kobayashi, Hisamine; Williams, John P; Lund, Jonathan; Greenhaff, Paul L; Smith, Kenneth; Atherton, Philip J

2017-09-23

Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13 C 6 -phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting. Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05). In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multi-centric universal pseudonymisation for secondary use of the EHR.

PubMed

Lo Iacono, Luigi

2007-01-01

This paper discusses the importance of protecting the privacy of patient data kept in an Electronic Health Record (EHR) in the case, where it leaves the control- and protection-sphere of the health care realm for secondary uses such as clinical or epidemiological research projects, health care research, assessment of treatment quality or economic assessments. The paper focuses on multi-centric studies, where various data sources are linked together using Grid technologies. It introduces a pseudonymisation system which enables a multi-centric universal pseudonymisation, meaning that a patient's identity will result in the same pseudonym, regardless of which participating study center the patient data is collected.

Rearing Tenebrio molitor L. (Coleptera: Tenebrionidae) in the "Lunar Palace 1" during a 105-day multi-crew closed integrative BLSS experiment.

PubMed

Li, Leyuan; Xie, Beizhen; Dong, Chen; Hu, Dawei; Wang, Minjuan; Liu, Guanghui; Liu, Hong

2015-11-01

Yellow mealworm (Tenebrio molitor L.) is one of the animal candidates for space bioregenerative life support systems. In this study, T. molitor was involved in a 105-day multi-crew closed integrative BLSS experiment for a tentative rearing study. The results showed that the overall bioconversion rate (ratio of T. molitor gained to the total feed consumed) of T. molitor reared in the closed system was 8.13%, while 78.43% of the feed was excreted as frass. T. molitor reared in the closed system had a good nutritional composition. The eight essential amino acids (EAAs) in T. molitor larvae accounted for 41.30% of its total amino acids, and most EAA contents were higher than the suggested amino acid pattern recommended by the FAO/WHO. T. molitor sample obtained in this work was high in polyunsaturated fatty acids, and low in saturated fatty acids, indicating that the composition of fatty acids was beneficial to human health. In the open environment outside the experimental system, we simultaneously reared three parallel groups of larval T. molitor using the same feeding regime and temperature condition. Compared with T. molitor reared in the open environment, larvae reared in the closed system grew slower. With the course of time t, the growth rate of T. molitor in the open environment was 0.839e(0.017t) times that of larvae in the closed system. This paper can provide data for future design and improvement of BLSS containing a T. molitor rearing unit. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Geochemistry of sulfur in the Florida Everglades; 1994 through 1999

USGS Publications Warehouse

Bates, Anne L.; Orem, W.H.; Harvey, J.W.; Spiker, E. C.

2000-01-01

In this report, we present data on the geochemistry of sulfur in sediments and in surface water, groundwater, and rainwater in the Everglades region in south Florida. The results presented here are part of a larger study intended to determine the roles played by the cycling of carbon, nitrogen, phosphorus, and sulfur in the ecology of the south Florida wetlands. The geochemistry of sulfur in the region is particularly important because of its link to the production of toxic methylmercury through processes mediated by sulfate reducing bacteria. Sediment cores were collected from the Everglades Agricultural Area (EAA), Water Conservation Areas (WCAs) 1A and 2A, from Lake Okeechobee, and from Taylor Slough in the southern Everglades. Water collection was more widespread and includes surface water from WCAs 1A, 2A, 3A, 2B, the EAA, Taylor Slough, Lake Okeechobee, and the Kissimmee River. Groundwater was collected from The Everglades Nutrient Removal Area (ENR) and from WCA 2A. Rainwater was collected at two month intervals over a period of one year from the ENR and from WCA 2A. Water was analyzed for sulfate concentration and sulfate sulfur stable isotopic ratio (34S/32S). Sediment cores were analyzed for total sulfur concentration and/or for concentrations of sulfur species (sulfate, organic sulfur, disulfides, and acid volatile sulfides (AVS)) and for their stable sulfur isotopic ratio. Results show a decrease in total sulfur content (1.57 to 0.61 percent dry weight) with depth in two sediment cores collected in WCA 2A, indicating that there has been an increase in total sulfur content in recent times. A sediment core from the center of Lake Okeechobee shows a decrease in total sulfur content with depth (0.28 to 0.08 percent dry weight). A core from the periphery of the lake (South Bay) likewise shows a decrease in total sulfur content with depth (1.00 to 0.69 percent dry weight), however, the overall sulfur content is greater than that near the center at all depths. This suggests input of sulfur in recent times, especially near the lake margins. Sediments show a general decrease in sulfur concentration with depth, probably because of increases in sulfur input to the marshes in recent times. Regional differences in the concentrations and stable isotopic ratios of sulfate sulfur in surface water show that sulfur contamination to the northern Everglades likely originates from canals draining the EAA.

Toward a feline-optimized culture medium: impact of ions, carbohydrates, essential amino acids, vitamins, and serum on development and metabolism of in vitro fertilization-derived feline embryos relative to embryos grown in vivo.

PubMed

Herrick, Jason R; Bond, Jennifer B; Magarey, Genevieve M; Bateman, Helen L; Krisher, Rebecca L; Dunford, Susan A; Swanson, William F

2007-05-01

The objective of this study was to define the physiologic needs of domestic cat embryos to facilitate development of a feline-specific culture medium. In a series of factorial experiments, in vivo-matured oocytes (n = 2040) from gonadotropin-treated domestic cats were inseminated in vitro to generate embryos (n = 1464) for culture. In the initial study, concentrations of NaCl (100.0 vs. 120.0 mM), KCl (4.0 vs. 8.0 mM), KH(2)PO(4) (0.25 vs. 1.0 mM), and the ratio of CaCl(2) to MgSO(4)-7H(2)O (1.0:2.0 mM vs. 2.0:1.0 mM) in the medium were evaluated during Days 1-6 (Day 0: oocyte recovery and in vitro fertilization [IVF]) of culture. Subsequent experiments assessed the effects of varying concentrations of carbohydrate (glucose, 1.5, 3.0, or 6.0 mM; l-lactate, 3.0, 6.0, or 12.0 mM; and pyruvate, 0.1 or 1.0 mM) and essential amino acids (EAAs; 0, 0.5, or 1.0x) in the medium during Days 1-3 and Days 3-6 of culture. Inclusion of vitamins (0 vs. 1.0x) and fetal calf serum (FCS; 0 vs. 5% [v/v]) in the medium also was evaluated during Days 3-6. Development and metabolism of IVF embryos on Day 3 or Day 6 were compared to age-matched in vivo embryos recovered from naturally mated queens. A feline-optimized culture medium (FOCM) was formulated based on these results (100.0 mM NaCl, 8.0 mM KCl, 1.0 mM KH(2)PO(4), 2.0 mM CaCl(2), 1.0 mM MgSO(4), 1.5 mM glucose, 6.0 mM L-lactate, 0.1 mM pyruvate, and 0x EAAs with 25.0 mM NaHCO(3), 1.0 mM alanyl-glutamine, 0.1 mM taurine, and 1.0x nonessential amino acids) with 0.4% (w/v) BSA from Days 0-3 and 5% FCS from Days 3-6. Using this medium, ~70% of cleaved embryos developed into blastocysts with profiles of carbohydrate metabolism similar to in vivo embryos. Our results suggest that feline embryos have stage-specific responses to carbohydrates and are sensitive to EAAs but are still reliant on one or more unidentified components of FCS for optimal blastocyst development.

Dietary management of urea cycle disorders: European practice.

PubMed

Adam, S; Almeida, M F; Assoun, M; Baruteau, J; Bernabei, S M; Bigot, S; Champion, H; Daly, A; Dassy, M; Dawson, S; Dixon, M; Dokoupil, K; Dubois, S; Dunlop, C; Evans, S; Eyskens, F; Faria, A; Favre, E; Ferguson, C; Goncalves, C; Gribben, J; Heddrich-Ellerbrok, M; Jankowski, C; Janssen-Regelink, R; Jouault, C; Laguerre, C; Le Verge, S; Link, R; Lowry, S; Luyten, K; Macdonald, A; Maritz, C; McDowell, S; Meyer, U; Micciche, A; Robert, M; Robertson, L V; Rocha, J C; Rohde, C; Saruggia, I; Sjoqvist, E; Stafford, J; Terry, A; Thom, R; Vande Kerckhove, K; van Rijn, M; van Teeffelen-Heithoff, A; Wegberg, A van; van Wyk, K; Vasconcelos, C; Vestergaard, H; Webster, D; White, F J; Wildgoose, J; Zweers, H

2013-12-01

There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required. © 2013 Elsevier Inc. All rights reserved.

CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.

1996-03-01

Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodesmore » (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.« less

Capture and characterization of particulate phosphorus from farm drainage waters in the Everglades Agricultural Area

NASA Astrophysics Data System (ADS)

Bhadha, J. H.; Lang, T.; Daroub, S.

2012-12-01

The buildup of highly labile, organic, phosphorus (P)-enriched sediments in farms canals within the Everglades Agricultural Area (EAA) has been associated with the production of floating aquatic vegetation. During drainage events, these sediments are susceptible to transport and contribute to the overall P load. In order to evaluate the total P load exiting the farm canals, a settling tank experiment was conducted to capture the sediments during drainage events from eight farms. Drainage water was channelized through two 200L polypropylene collection tanks which allowed sediments to settle at the bottom based on its particle size. Water was carefully siphoned out of the tanks and the sediments collected for analyses. A five step P-fractionation process was used to distinguish organic (o) and inorganic (i) forms of P: KCl extractable P, NaOH extractable P, HCl extractable P, and residual P. The KCl-Pi fraction represents the labile Pi that is water soluble and exchangeable (loosely adsorbed); NaOH extractable P represents Fe- and Al- bound inorganic P (NaOH-Pi) and organic P associated with humic and fulvic acids (NaOH-Po). The HCl-Pi fraction includes Ca- and Mg- bound P, while Residue-P represents recalcitrant organic P compounds and P bound to minerals. The sediments were also used to conduct a P-flux study under both aerobic and anaerobic conditions. Our goal is to provide growers with vital information and insight into P loading that will help them in their efforts to reduce off-farm P loads in the EAA.

Prognostic value of baseline absolute lymphocyte concentration and neutrophil/lymphocyte ratio in dogs with newly diagnosed multi-centric lymphoma.

PubMed

Mutz, M; Boudreaux, B; Kearney, M; Stroda, K; Gaunt, S; Shiomitsu, K

2015-12-01

Canine multi-centric B-cell lymphoma shares similarities with diffuse large B-cell (Non-Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi-centric lymphoma. Medical records of 77 dogs with multi-centric lymphoma treated with a CHOP-based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre-treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression-free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance. © 2013 John Wiley & Sons Ltd.

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma.

PubMed

Daters, A T; Mauldin, G E; Mauldin, G N; Brodsky, E M; Post, G S

2010-03-01

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

77 FR 6782 - In the Matter of: Kok Tong Lim, a/k/a Thomas Lim Blk 258A Compassvale Road #07-551 Singapore...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... (50 U.S.C. 1701 et seq. (2000)) (``IEEPA''). Specifically, Lim conspired to illegally export wound... the Internal Security Act of 1950 (50 U.S.C. 783(b)), or section 38 of the Arms Export Control Act (22... Export Administration Act (50 U.S.C. app. Sec. Sec. 2401-2420 (2000)) (``EAA''). Since August 21, 2001...

U.S. Combat Commands’ Participation in the Proliferation Security Initiative: A Training Manual

DTIC Science & Technology

2009-01-01

cadmium-zinc- tellurium DHS Department of Homeland Security DoD Department of Defense EAA Export Administration Act EAR Export Administration Regulations EU...Pulsed fast neutron analysis PSI Proliferation Security Initiative Pu Plutonium SCO Shanghai Cooperation Organization SFI Security Freight Initiative...resolution) sodium iodide (NaI) and (intermediate-resolution) cadmium-zinc- tellurium (CZT) detectors may not have the energy resolution and/or sensitivity

Acoustic Scattering Models of Zooplankton and Microstructure

DTIC Science & Technology

1999-09-30

1998, a remotely operated vehicle was used to deploy acoustic transducers so that the acoustic scattering by siphonophores , a gas-bearing animal, could...their high frequency acoustics systems. 4) In addition, we have identified two types of zooplankton ( siphonophores and pteropods) that have high...Benfield, P.H. Wiebe, and D. Chu, 1999. “In situ measurements of acoustic target strengths of siphonophores ,” Proceedings of the 2nd EAA

Export Controls: License Screening and Compliance Procedures Need Strengthening.

DTIC Science & Technology

1994-06-01

agreements between Commerce and Customs . While this represents a significant step towards a cooperative relationship , we have not verified that real...license applications, (2) how well these agencies cooperate with each other and the U.S. Customs Service, (3) whether State is monitoring reexports...other than a foreign government). Customs serves as State’s enforcement arm for AECA. In contrast, EAA has no registration or U.S. person

Position statement and guidelines on support personnel in audiology. American Speech-Language Hearing Association.

PubMed

1998-01-01

This policy document of the American Speech-Language-Hearing Association (ASHA) reflects the Association's position that the Certificate of Clinical Competence-Audiology (CCC-A) is a nationally recognized quality indicator and education standard for the profession. The following statement includes the CCC-A as the appropriate credential for audiologists supervising support personnel. The consensus panel document's exclusion of the CCC-A conflicts with ASHA's policy. Member organizations that composed the consensus panel on support personnel in audiology included: Academy of Dispensing Audiologists (ADA), American Academy of Audiology (AAA), ASHA, Educational Audiology Association (EAA), Military Audiology Association (MAA), and the National Hearing Conservation Association (NHCA). Representatives to the panel included Donald Bender (AAA) and Evelyn Cherow (ASHA), co-chairs; James McDonald and Meredy Hase (ADA); Albert deChiccis and Cheryl deConde Johnson (AAA); Chris Halpin and Deborah Price (ASHA); Peggy Benson (EAA); James Jerome (MAA); and Lloyd Bowling and Richard Danielson (NHCA). ASHA's Legislative Council and Executive Board elected not to adopt the consensus panel document because it excluded the CCC-A. In all others aspects, the documents remain similar. This position statement and guidelines supersede the audiology sections of the Guidelines for the Employment and Utilization of Supportive Personnel (LC 32-80).

The neurochemical basis of photic entrainment of the circadian pacemaker

NASA Technical Reports Server (NTRS)

Rea, Michael A.; Buckley, Becky; Lutton, Lewis M.

1992-01-01

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues.

Nutritional evaluation of caseins and whey proteins and their hydrolysates from Protamex*

PubMed Central

Sindayikengera, Séverin; Xia, Wen-shui

2006-01-01

Whey protein concentrate (WPC 80) and sodium caseinate were hydrolyzed by Protamex to 5%, 10%, 15%, and 20% degree of hydrolysis (DH). WPC 80, sodium caseinate and their hydrolysates were then analyzed, compared and evaluated for their nutritional qualities. Their chemical composition, protein solubility, amino acid composition, essential amino acid index (EAA index), biological value (BV), nutritional index (NI), chemical score, enzymic protein efficiency ratio (E-PER) and in vitro protein digestibility (IVPD) were determined. The results indicated that the enzymatic hydrolysis of WPC 80 and sodium caseinate by Protamex improved the solubility and IVPD of their hydrolysates. WPC 80, sodium caseinate and their hydrolysates were high-quality proteins and had a surplus of essential amino acids compared with the FAO/WHO/UNU (1985) reference standard. The nutritive value of WPC 80 and its hydrolysates was superior to that of sodium caseinate and its hydrolysates as indicated by some nutritional parameters such as the amino acid composition, chemical score, EAA index and predicted BV. However, the E-PER was lower for the WPC hydrolysates as compared to unhydrolyzed WPC 80 but sodium caseinate and its hydrolysates did not differ significantly. The nutritional qualities of WPC 80, sodium caseinate and their hydrolysates were good and make them appropriate for food formulations or as nutritional supplements. PMID:16421963

International Society of Sports Nutrition Position Stand: protein and exercise.

PubMed

Jäger, Ralf; Kerksick, Chad M; Campbell, Bill I; Cribb, Paul J; Wells, Shawn D; Skwiat, Tim M; Purpura, Martin; Ziegenfuss, Tim N; Ferrando, Arny A; Arent, Shawn M; Smith-Ryan, Abbie E; Stout, Jeffrey R; Arciero, Paul J; Ormsbee, Michael J; Taylor, Lem W; Wilborn, Colin D; Kalman, Doug S; Kreider, Richard B; Willoughby, Darryn S; Hoffman, Jay R; Krzykowski, Jamie L; Antonio, Jose

2017-01-01

The International Society of Sports Nutrition (ISSN) provides an objective and critical review related to the intake of protein for healthy, exercising individuals. Based on the current available literature, the position of the Society is as follows:An acute exercise stimulus, particularly resistance exercise, and protein ingestion both stimulate muscle protein synthesis (MPS) and are synergistic when protein consumption occurs before or after resistance exercise.For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4-2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein.Higher protein intakes (2.3-3.1 g/kg/d) may be needed to maximize the retention of lean body mass in resistance-trained subjects during hypocaloric periods.There is novel evidence that suggests higher protein intakes (>3.0 g/kg/d) may have positive effects on body composition in resistance-trained individuals (i.e., promote loss of fat mass).Recommendations regarding the optimal protein intake per serving for athletes to maximize MPS are mixed and are dependent upon age and recent resistance exercise stimuli. General recommendations are 0.25 g of a high-quality protein per kg of body weight, or an absolute dose of 20-40 g.Acute protein doses should strive to contain 700-3000 mg of leucine and/or a higher relative leucine content, in addition to a balanced array of the essential amino acids (EAAs).These protein doses should ideally be evenly distributed, every 3-4 h, across the day.The optimal time period during which to ingest protein is likely a matter of individual tolerance, since benefits are derived from pre- or post-workout ingestion; however, the anabolic effect of exercise is long-lasting (at least 24 h), but likely diminishes with increasing time post-exercise.While it is possible for physically active individuals to obtain their daily protein requirements through the consumption of whole foods, supplementation is a practical way of ensuring intake of adequate protein quality and quantity, while minimizing caloric intake, particularly for athletes who typically complete high volumes of training. Rapidly digested proteins that contain high proportions of essential amino acids (EAAs) and adequate leucine, are most effective in stimulating MPS. Different types and quality of protein can affect amino acid bioavailability following protein supplementation. Athletes should consider focusing on whole food sources of protein that contain all of the EAAs (i.e., it is the EAAs that are required to stimulate MPS). Endurance athletes should focus on achieving adequate carbohydrate intake to promote optimal performance; the addition of protein may help to offset muscle damage and promote recovery. Pre-sleep casein protein intake (30-40 g) provides increases in overnight MPS and metabolic rate without influencing lipolysis.

Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas.

PubMed

Hayes, Josie; Yu, Yao; Jalbert, Llewellyn E; Mazor, Tali; Jones, Lindsey E; Wood, Matthew D; Walsh, Kyle M; Bengtsson, Henrik; Hong, Chibo; Oberndorfer, Stefan; Roetzer, Thomas; Smirnov, Ivan V; Clarke, Jennifer L; Aghi, Manish K; Chang, Susan M; Nelson, Sarah J; Woehrer, Adelheid; Phillips, Joanna J; Solomon, David A; Costello, Joseph F

2018-04-09

Rare multicentric lower-grade gliomas (LGGs) represent a unique opportunity to study the heterogeneity among distinct tumor foci in a single patient and to infer their origins and parallel patterns of evolution. In this study, we integrate clinical features, histology, and immunohistochemistry for 4 patients with multicentric LGG, arising both synchronously and metachronously. For 3 patients we analyze the phylogeny of the lesions using exome sequencing, including one case with a total of 8 samples from the 2 lesions. One patient was diagnosed with multicentric isocitrate dehydrogenase 1 (IDH1) mutated diffuse astrocytomas harboring distinct IDH1 mutations, R132H and R132C; the latter mutation has been associated with Li-Fraumeni syndrome, which was subsequently confirmed in the patient's germline DNA and shown in additional cases with The Cancer Genome Atlas data. In another patient, phylogenetic analysis of synchronously arising grade II and grade III diffuse astrocytomas demonstrated a single shared mutation, IDH1 R132H, and revealed convergent evolution via non-overlapping mutations in ATRX and TP53. In 2 cases, there was divergent evolution of IDH1-mutated and 1p/19q-codeleted oligodendroglioma and IDH1-mutated and 1p/19q-intact diffuse astrocytoma, occurring synchronously in one case and metachronously in a second. Each tumor in multicentric LGG cases may arise independently or may diverge very early in their development, presenting as genetically and histologically distinct tumors. Comprehensive sampling of these lesions can therefore significantly alter diagnosis and management. Additionally, somatic IDH1 R132C mutation in either multicentric or solitary LGG identifies unsuspected germline TP53 mutation, validating the limited number of published cases.

Light-Induced Alterations in Basil Ganglia Kynurenic Acid Levels

NASA Technical Reports Server (NTRS)

Sroufe, Angela E.; Whittaker, J. A.; Patrickson, J. W.; Orr, M. C.

1997-01-01

The metabolic synthesis, release and breakdown of several known CNS neurotransmitters have been shown to follow a circadian pattern entrained to the environmental light/dark cycle. The levels of excitatory amino acid (EAA) transmitters such as glutamate, have been shown to vary with environmental lighting conditions. Kynurenic Acid (KA), an endogenous tryptophan metabolite and glutamate receptor antagonist, has been reported to have neuroprotective effects against EAA-induced excitotoxic cell damage. Changes in KA's activity within the mammalian basal ganglia has been proposed as being contributory to neurotoxicity in Huntington's Disease. It is not known whether CNS KA levels follow a circadian pattern or exhibit light-induced fluctuations. However, because the symptoms of certain degenerative motor disorders seem to fluctuate with daily 24 hour rhythm, we initiated studies to determine if basal ganglia KA were influenced by the daily light/dark cycle and could influence motor function. Therefore in this study, HPLC-EC was utilized to determine if basal ganglia KA levels in tissue extracts from adult male Long-Evans rats (200-250g) entrained to 24 and 48 hours constant light and dark conditions, respectively. Samples were taken one hour before the onset of the subjective day and one hour prior to the onset of the subjective night in order to detect possible phase differences in KA levels and to allow for accumulation of factors expressed in association with the light or dark phase. Data analysis revealed that KA levels in the basal ganglia vary with environmental lighting conditions; being elevated generally during the dark. Circadian phase differences in KA levels were also evident during the subjective night and subjective day, respectively. Results from these studies are discussed with respect to potential cyclic changes in neuronal susceptibility to excitotoxic damage during the daily 24 hour cycle and its possible relevance to future therapeutic approaches in treating neurodegenerative disorders.

Biochemical composition of the alligator pipefish, Syngnathoides biaculeatus (Bloch, 1785)

NASA Astrophysics Data System (ADS)

Sanaye, Sushant Vilas; Pawar, Ashwini Pandurang; Rivonker, Chandrasheker Umanath; Sreepada, Rayadurga Anantha; Ansari, Zakir Ali; Ram, Anirudh

2017-11-01

Considering the economic importance in traditional Chinese medicine (TCM) and lack of baseline information, we evaluated the proximate composition, fatty acid and amino acid profiles, trace element content and C:N ratio in the alligator pipefish, Syngnathoides biaculeatus. Amongst proximate principals, a crude protein formed the major biochemical component ((58.9±2.2)% dry weight). Mean percent concentrations (dry weight) of other components such as a total lipid (TL), ash and nitrogen-free extract measured were, (1.8±0.2)%, (19.2±2.2)% and (20.1±0.45)%, respectively. The fatty acid profile revealed the presence of 27 saturated fatty acids (SFA) with 13 straight-chained and 14 branched-chained, 28 unsaturated fatty acids (UFA) with 14 monounsaturated and 14 polyunsaturated and nine other minor fatty acids. Mean percent contributions of total SFAs and UFAs to TL were found to be (55.41±0.24)% and (44.05±0.25)%, respectively. Altogether, 16 different amino acids with an equal number of essential (EAA) and non-essential (NAA) ones were identified. Percent contributions by EAA and NAA to the total amino acid content were 38.11% and 61.89%, respectively. Trace metal concentrations in S. biaculeatus were generally low and their distribution followed the order, Mg>Fe>Zn>Mn>Cu>Cr>Ni>Hg>Co. The C:N ratio was (4.37±0.04)%. The profile of major biochemical constituents in alligator pipefish, S. biaculeatus revealed its potential use in TCM as well as a nutritional diet for human consumption. The results of the study would also form the basis for formulation and optimization of diets for the culture of S. biaculeatus.

Comparative Genomics of the Dual-Obligate Symbionts from the Treehopper, Entylia carinata (Hemiptera: Membracidae), Provide Insight into the Origins and Evolution of an Ancient Symbiosis.

PubMed

Mao, Meng; Yang, Xiushuai; Poff, Kirsten; Bennett, Gordon

2017-06-01

Insect species in the Auchenorrhyncha suborder (Hemiptera) maintain ancient obligate symbioses with bacteria that provide essential amino acids (EAAs) deficient in their plant-sap diets. Molecular studies have revealed that two complementary symbiont lineages, "Candidatus Sulcia muelleri" and a betaproteobacterium ("Ca. Zinderia insecticola" in spittlebugs [Cercopoidea] and "Ca. Nasuia deltocephalinicola" in leafhoppers [Cicadellidae]) may have persisted in the suborder since its origin ∼300 Ma. However, investigation of how this pair has co-evolved on a genomic level is limited to only a few host lineages. We sequenced the complete genomes of Sulcia and a betaproteobacterium from the treehopper, Entylia carinata (Membracidae: ENCA), as the first representative from this species-rich group. It also offers the opportunity to compare symbiont evolution across a major insect group, the Membracoidea (leafhoppers + treehoppers). Genomic analyses show that the betaproteobacteria in ENCA is a member of the Nasuia lineage. Both symbionts have larger genomes (Sulcia = 218 kb and Nasuia = 144 kb) than related lineages in Deltocephalinae leafhoppers, retaining genes involved in basic cellular functions and information processing. Nasuia-ENCA further exhibits few unique gene losses, suggesting that its parent lineage in the common ancestor to the Membracoidea was already highly reduced. Sulcia-ENCA has lost the abilities to synthesize menaquinone cofactor and to complete the synthesis of the branched-chain EAAs. Both capabilities are conserved in other Sulcia lineages sequenced from across the Auchenorrhyncha. Finally, metagenomic sequencing recovered the partial genome of an Arsenophonus symbiont, although it infects only 20% of individuals indicating a facultative role. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Comparative Genomics of the Dual-Obligate Symbionts from the Treehopper, Entylia carinata (Hemiptera: Membracidae), Provide Insight into the Origins and Evolution of an Ancient Symbiosis

PubMed Central

Yang, Xiushuai; Poff, Kirsten; Bennett, Gordon

2017-01-01

Abstract Insect species in the Auchenorrhyncha suborder (Hemiptera) maintain ancient obligate symbioses with bacteria that provide essential amino acids (EAAs) deficient in their plant-sap diets. Molecular studies have revealed that two complementary symbiont lineages, “Candidatus Sulcia muelleri” and a betaproteobacterium (“Ca. Zinderia insecticola” in spittlebugs [Cercopoidea] and “Ca. Nasuia deltocephalinicola” in leafhoppers [Cicadellidae]) may have persisted in the suborder since its origin ∼300 Ma. However, investigation of how this pair has co-evolved on a genomic level is limited to only a few host lineages. We sequenced the complete genomes of Sulcia and a betaproteobacterium from the treehopper, Entylia carinata (Membracidae: ENCA), as the first representative from this species-rich group. It also offers the opportunity to compare symbiont evolution across a major insect group, the Membracoidea (leafhoppers + treehoppers). Genomic analyses show that the betaproteobacteria in ENCA is a member of the Nasuia lineage. Both symbionts have larger genomes (Sulcia = 218 kb and Nasuia = 144 kb) than related lineages in Deltocephalinae leafhoppers, retaining genes involved in basic cellular functions and information processing. Nasuia-ENCA further exhibits few unique gene losses, suggesting that its parent lineage in the common ancestor to the Membracoidea was already highly reduced. Sulcia-ENCA has lost the abilities to synthesize menaquinone cofactor and to complete the synthesis of the branched-chain EAAs. Both capabilities are conserved in other Sulcia lineages sequenced from across the Auchenorrhyncha. Finally, metagenomic sequencing recovered the partial genome of an Arsenophonus symbiont, although it infects only 20% of individuals indicating a facultative role. PMID:28854637

Microgravity

NASA Image and Video Library

1999-08-03

SPD representative Steve Lambing shows the PentaPure water purification unit to some EAA visitors. The Microgravity Research and the Space Product Development Programs joined with the Johnson Space Center (JSC) for a first time ever ISS/Microgravity Research space-focused exhibit at Oshkosh AirVenture'99 from July 28-August 3, 1999. The Space Product Development (SPD) display included the STS-95 ASTROCULTURE training hardware used by John Glenn and his crewmates, a PentaPure water purfication system, and a Ford engine block.

Sulfur, a Key Water Quality Issue in the Everglades

NASA Astrophysics Data System (ADS)

Orem, W. H.; Lerch, H. E.; Bates, A. L.; Corum, M.; Beck, M.; Kleckner, S.

2002-05-01

Sulfur is an important water quality issue in the Everglades because of its role in microbial sulfate reduction and the methylation of mercury. Methylmercury (MeHg), a neurotoxin that is bioaccumulated, has been found in high concentrations in freshwater fish from the Everglades, and poses a potential threat to fish-eating wildlife and to human health through fish consumption. Sulfur appears to play a key role in regulating both the magnitude and distribution of MeHg in the Everglades. Freshwater wetlands typically have low sulfur concentrations, but marshes in portions of the northern Everglades have average surface water sulfate concentrations of 60 mg/l, compared to 1 mg/l or less at background sites. Marsh areas with excess sulfate are concentrated near sites of canal discharge and along canal levees. The canal water that is discharged into the marshes appears to be the major source of excess sulfate entering the Everglades. This canal water drains the Everglades Agricultural Area (EAA) and has sulfate concentrations averaging over 70 mg/l and periodically approaching 200 mg/l. We used sulfate concentration data and the sulfur (d34S) isotopic composition of sulfate in marsh surface water, canal water, rainwater, and groundwater to trace the source of the excess sulfate entering the Everglades. Results show that canal water from the EAA is the major source of excess sulfate entering the Everglades. Furthermore, canal water with the highest sulfate concentrations had d34S values of +16 per mil, similar to the d34S signature of agricultural sulfur used as a soil amendment in the EAA. Rainwater has too little sulfate to account for the high sulfate concentrations observed in the canals and in large portions of the Everglades. Groundwater beneath the present day Everglades generally has either too low a sulfate concentration or a d34S signature that is inconsistent with that of surface water in the Everglades. The excess sulfate entering the Everglades from canal discharge stimulates sulfate reduction and sulfide buildup in the sediments. This lowers redox potentials in sulfur-contaminated areas to values more reducing than natural, which may affect macrophyte growth in the Everglades by limiting oxygen penetration to roots. Excess sulfur has two differential effects with respect to MeHg production: stimulation through increased sulfate reduction, and inhibition through buildup of excess sulfide in sediment porewater. The balance between these two effects influences the magnitude and distribution of MeHg production in the Everglades. Results from this study and research of others suggest that the MeHg problem in the Everglades results largely from two factors: (1) increased fallout of mercury on the ecoxyxtem, and (2) sulfur contamination of the ecosystem from agricultural runoff.

Are power calculations useful? A multicentre neuroimaging study

PubMed Central

Suckling, John; Henty, Julian; Ecker, Christine; Deoni, Sean C; Lombardo, Michael V; Baron-Cohen, Simon; Jezzard, Peter; Barnes, Anna; Chakrabarti, Bhismadev; Ooi, Cinly; Lai, Meng-Chuan; Williams, Steven C; Murphy, Declan GM; Bullmore, Edward

2014-01-01

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources. PMID:24644267

Ethical dilemmas of a large national multi-centre study in Australia: time for some consistency.

PubMed

Driscoll, Andrea; Currey, Judy; Worrall-Carter, Linda; Stewart, Simon

2008-08-01

To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large-scale national multi-centre clinical audit called the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study. Multi-centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects. The National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes study used an investigator-developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence-based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC. Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six- to eight-month delay in commencing the national study. Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi-centre research which is now normative process for health services. The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi-centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

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

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) 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. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre 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 seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant 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. PMID:23683829

[Sentinel node biopsy in patients with multifocal and multicentric breast cancer: A 5-year follow-up].

PubMed

Blanco Saiz, I; López Carballo, M T; Martínez Fernández, J; Carrión Maldonado, J; Cabrera Pereira, A; Moral Alvarez, S; Santamaría Girón, L; Cantero Cerquella, F; López Secades, A; Díaz González, D; Llaneza Folgueras, A; Aira Delgado, F J

2014-01-01

Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32-126 months). Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes was observed than in the unifocal group (11.7% vs 5.4%) as well as a significantly higher number of SN per patient (1.70 vs 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs 93.1%), and the finding of extra-axillary drainages was higher (20% vs 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.

PubMed

Nyangoh Timoh, Krystel; Stewart, Zelda; Benjoar, Mikhael; Beldjord, Selma; Ballester, Marcos; Bazot, Marc; Thomassin-Naggara, Isabelle; Darai, Emile

To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis. A prospective study (Canadian Task Force classification II-2). Tenon University Hospital, Paris, France. Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included. Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections. The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61). MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosis than conventional MRI. Copyright © 2018. Published by Elsevier Inc.

Naval Law Review, Volume 54, 2007

DTIC Science & Technology

2007-01-01

Aging Beauty: the Cox Commission Recommendations to Rejuvenate the Uniform Code of Military Justice, 2002 L. REV. M.S.U.-D.C.L. 111 While the accused...at 1037-38 (2003). See generally NATIONAL ACADEMY OF SCIENCES, BIOTECHNOLOGY RESEARCH IN AN AGE OF TERRORISM 46 (2004). 93 See “The Debate over BWC...EAA to expire in 2001 (50 U.S.C. app. § 2419) and, at the time of this writing, had not yet renewed the act or replaced it with a suitable substitute

Theory of Dielectric Elastomers

DTIC Science & Technology

2010-10-25

partly in the air and partly in a dielectric liquid . The applied voltage causes the liquid to rise to a height h. The height results from the...balance of the Maxwell stress and the weight of the liquid . The Maxwell stress parallel to the electrodes in the air is 2/2Eaa   , where a is the...permittivity of the air. The Maxwell stress parallel to the electrodes in the liquid is 2/2Ell   , where l is the permittivity of the liquid

Treatment of unicentric and multicentric Castleman disease and the role of radiotherapy.

PubMed

Chronowski, G M; Ha, C S; Wilder, R B; Cabanillas, F; Manning, J; Cox, J D

2001-08-01

Although surgery is considered standard therapy for unicentric Castleman disease, favorable responses to radiotherapy also have been documented. The authors undertook this study to analyze the clinical factors, treatment approaches, and outcomes of patients with unicentric or multicentric Castleman disease, and to report the outcomes of patients with unicentric Castleman disease treated with radiotherapy. The authors reviewed the medical records of 22 patients who had received a histologic diagnosis of Castleman disease at the University of Texas M. D. Anderson Cancer Center between 1988 and 1999. One patient with a concurrent histopathologic diagnosis of nonsecretory multiple myeloma was excluded from the study. In all patients, the diagnosis of Castleman disease was based on the results of lymph node biopsies. Disease was categorized as being either unicentric or multicentric and further subdivided into hyaline vascular, plasma cell, or mixed variant histologic types. Clinical variables and outcomes were analyzed according to treatment, which consisted of surgery, chemotherapy, or radiotherapy. Records from 21 patients were analyzed: 12 had unicentric disease, and 9 had multicentric disease. The mean follow-up time for the entire series was 51 months (median, 40 months). Four patients with unicentric disease were treated with radiotherapy alone: 2 remain alive and symptom free, 2 died of causes unrelated to Castleman disease and had no evidence of disease at last follow-up. Eight patients with unicentric disease were treated with complete or partial surgical resection, and all are alive and asymptomatic. All nine patients with multicentric disease were treated with combination chemotherapy: five are alive with no evidence of disease, and four are alive with progressive disease. Surgery results in excellent rates of cure in patients with unicentric Castleman disease; radiotherapy can also achieve clinical response and cure in selected patients. Multicentric Castleman disease is a more aggressive clinical entity and is most effectively treated with combination chemotherapy, whereas the role of radiotherapy in its treatment remains unclear. Copyright 2001 American Cancer Society.

Multicentric myelolipoma in a dog.

PubMed

Kamiie, Junichi; Fueki, Keisuke; Amagai, Harumi; Ichikawa, Youichiro; Shirota, Kinji

2009-03-01

We report herein a case of multicentric myelolipoma in an 11-year-old beagle dog that presented with vomiting. Laparotomy demonstrated the presence of a large mass adherent to the greater omentum and multiple small white maculae in the spleen. Cytological and histological examinations revealed that the mass and maculae comprised mature adipocytes and hematopoietic elements including granulocytic, erythrocytic and megakaryocytic series in several phases of maturation and macrophages containing hemosiderin deposits, resembling bone marrow. Multicentric myelolipoma was diagnosed. This is first report of multicentric myelolipoma in a dog.

Evaluation of sentinel lymph node biopsy prior to axillary lymph node dissection: the role of isolated tumor cells/micrometastases and multifocality/multicentricity-a retrospective study of 1214 breast cancer patients.

PubMed

Schröder, Lars; Fricker, Roland; Stein, Roland Gregor; Rink, Thomas; Fitz, Hartmut; Blasius, Sebastian; Wöckel, Achim; Müller, Thomas

2018-06-01

Sentinel lymph node biopsy (SLNB) alone has thus become an accepted surgical approach for patients with limited axillary metastatic disease. We investigated to what extent isolated tumor cells (ITC) or micrometastasis in SLNBs is associated with proven tumor cells or metastasis in non-sentinel lymph nodes. Furthermore, we investigated the feasibility of SLNB in multifocal and multicentric tumors as both entities have been considered a contraindication for this technique. 1214 women suffering from T1 and T2 invasive breast cancer, with clinically and sonographically insuspect axillary status and undergoing primary breast cancer surgery including SLNB and axillary staging in case of SLN (sentinel lymph node) metastases, were recruited into this multicentered study. ITC and micrometastases were found in 2.01 and 21.4% of patients with SLN metastases (n = 299). Among patients with sentinel micrometastases, 4.7% showed further axillary micrometastases, while only two patients (3.1%) had two axillary macrometastases. Multifocal and multicentric tumors were diagnosed in 9.3 and 2.6% of our patients who at least had one SLN resected, respectively. Detection rates of SLNs did not differ between the cohorts suffering from unicentric and multifocal or multicentric disease. Moreover, the portion of tumor-free SLNs, the number of SLNs with metastasis as well as the mean number of resected SLNs did not differ. No patient with sentinel node micrometastases showed more than two axillary macrometastases. Multifocal and multicentric disease is no contraindication for SLNB.

Recommendations of the VAC2VAC workshop on the design of multi-centre validation studies.

PubMed

Halder, Marlies; Depraetere, Hilde; Delannois, Frédérique; Akkermans, Arnoud; Behr-Gross, Marie-Emmanuelle; Bruysters, Martijn; Dierick, Jean-François; Jungbäck, Carmen; Kross, Imke; Metz, Bernard; Pennings, Jeroen; Rigsby, Peter; Riou, Patrice; Balks, Elisabeth; Dobly, Alexandre; Leroy, Odile; Stirling, Catrina

2018-03-01

Within the Innovative Medicines Initiative 2 (IMI 2) project VAC2VAC (Vaccine batch to vaccine batch comparison by consistency testing), a workshop has been organised to discuss ways of improving the design of multi-centre validation studies and use the data generated for product-specific validation purposes. Moreover, aspects of validation within the consistency approach context were addressed. This report summarises the discussions and outlines the conclusions and recommendations agreed on by the workshop participants. Copyright © 2018.

[Tumor markers for bladder cancer: up-to-date study by the Kiel Tumor Bank].

PubMed

Hautmann, S; Eggers, J; Meyhoff, H; Melchior, D; Munk, A; Hamann, M; Naumann, M; Braun, P M; Jünemann, K P

2007-11-01

The number of noninvasive diagnostic tests for bladder cancer has increased tremendously over the last years with a large number of experimental and commercial tests. Comparative analyses of tests for diagnosis, follow-up, and recurrence detection of bladder cancer were performed retrospectively as well as prospectively, unicentrically, and multicentrically. An analysis of multicentric studies with large patient numbers compared with our own Kiel Tumor Bank data is presented. The Kiel Tumor Bank data looked prospectively at 106 consecutive bladder tumor patients from the year 2006. Special focus was put on urine cytology as a reference test, as well as the commercial NMP 22 Bladder Chek. The analysis of the NMP 22 Bladder Chek showed an overall sensitivity of 69% for all tumor grades and stages, with a specificity of 76%. Comparison to multicentric data with an overall sensitivity of 75% for all tumor grades and stages, with a specificity of 73%, showed results similar to those in the literature. Urine cytology showed a comparable overall sensitivity of 73% for all tumor grades and stages, with a specificity of 80%. A large number of noninvasive tests for bladder cancer follow-up with reasonable sensitivity and specificity can currently be used. Because of limited numbers of prospective randomized multicentric studies, no single particular marker for bladder cancer screening can be recommended at this point in time.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study.

PubMed

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J; Huang, Wenlong; Kennedy, Jeffrey D; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M; VoB, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S C

2016-10-01

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP-all animals allocated to treatment; n = 249) and a selected population (SP-TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding "poor" burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of -374 g (-479 to -269 g) for TP and -498 g (-609 to -386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.

An outbreak of extrinsic alveolitis at a car engine plant.

PubMed

Dawkins, Paul; Robertson, Alastair; Robertson, Wendy; Moore, Vicky; Reynolds, John; Langman, Gerald; Robinson, Edward; Harris-Roberts, Joanne; Crook, Brian; Burge, Sherwood

2006-12-01

Twelve workers from a car engine-manufacturing plant presented with extrinsic allergic alveolitis (EAA), with heterogeneous clinical, radiological and pathological findings. They were exposed to metalworking fluids (MWF) that cooled, lubricated and cleaned the machines. They were characterized by history, examination, lung function testing, radiology, bronchoscopic lavage, lung biopsy and serology. Sera were tested for precipitins to a crude extract of used MWF and to reference cultures of bacteria suspected to be implicated. All were males and none were current smokers. All had dyspnoea, many had weight loss and cough, but only half had influenza-like symptoms. Only half had auscultatory crackles. Five had peak flow variability, four with an occupational component. There was overall restrictive spirometry, decreased lung volumes and reduced gas transfers. Ten had radiological evidence of interstitial lung disease. Seven (of eight) had lymphocytosis on bronchial lavage, including the two with inconclusive radiology. Seven (of 11) had lung biopsies showing inflammatory infiltrates, two with fibrosis and one with granulomas. Three (of 11) had strong positive precipitins to an extract of the used MWF from the plant. Molecular biological analysis of the MWF revealed Acinetobacter and Ochrobactrum. Precipitins to Acinetobacter were detected in seven of 11 workers tested (and four of 11 control workers). Precipitins to Ochrobactrum were detected in three of 11 workers tested (and three of 11 control workers). This is the largest series reported in Europe of EAA due to an aerosol of microbiologically contaminated MWF in heavy manufacturing industry.

Electron affinity and excited states of methylglyoxal

NASA Astrophysics Data System (ADS)

Dauletyarov, Yerbolat; Dixon, Andrew R.; Wallace, Adam A.; Sanov, Andrei

2017-07-01

Using photoelectron imaging spectroscopy, we characterized the anion of methylglyoxal (X2A″ electronic state) and three lowest electronic states of the neutral methylglyoxal molecule: the closed-shell singlet ground state (X1A'), the lowest triplet state (a3A″), and the open-shell singlet state (A1A″). The adiabatic electron affinity (EA) of the ground state, EA(X1A') = 0.87(1) eV, spectroscopically determined for the first time, compares to 1.10(2) eV for unsubstituted glyoxal. The EAs (adiabatic attachment energies) of two excited states of methylglyoxal were also determined: EA(a3A″) = 3.27(2) eV and EA(A1A″) = 3.614(9) eV. The photodetachment of the anion to each of these two states produces the neutral species near the respective structural equilibria; hence, the a3A″ ← X2A″ and A1A″ ← X2A″ photodetachment transitions are dominated by intense peaks at their respective origins. The lowest-energy photodetachment transition, on the other hand, involves significant geometry relaxation in the X1A' state, which corresponds to a 60° internal rotation of the methyl group, compared to the anion structure. Accordingly, the X1A' ← X2A″ transition is characterized as a broad, congested band, whose vertical detachment energy, VDE = 1.20(4) eV, significantly exceeds the adiabatic EA. The experimental results are in excellent agreement with the ab initio predictions using several equation-of-motion methodologies, combined with coupled-cluster theory.

A guide to multi-centre ethics for surgical research in Australia and New Zealand.

PubMed

Boult, Maggi; Fitzpatrick, Kate; Maddern, Guy; Fitridge, Robert

2011-03-01

This paper describes existing inconsistencies as well as the disparate processes and logistics required when obtaining ethics approval in Australia and New Zealand in order to initiate a multi-centre bi-national surgical trial. The endovascular aortic aneurysm repair trial is a large multi-centre trial that aims to obtain pre- and post-operative data from patients in hospitals across Australia and New Zealand. As the trial was research based, ethics applications were submitted to all hospitals where surgeons wished to be involved in the trial. Few ethics committees have embraced attempts to simplify the application process for multi-centre trials. There was limited mutual review between Human Research Ethics Committees necessitating the submission of multiple applications. Though the use of the National Ethics Application Form in ethical review is increasing, some Human Research Ethics Committees do not accept it in its entirety; many require site-specific applications or sections of the Common Application Form modules. Queensland, New South Wales and New Zealand were the easiest systems to prepare, submit and lodge ethics applications because of their understanding and accommodation of reviewing multi-centred trials. The time, expense and complexity of obtaining ethics approval for multi-centre research projects are impediments to their establishment and reduce the time available for research. Australia is working to implement a system named the Harmonisation of Multi-centre Ethical Review to ease the process of obtaining multi-centre ethics clearance. Our experience suggests there will be some teething problems with implementation and acceptance. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.

Measuring organic matter in Everglades wetlands and the Everglades Agricultural Area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Alan L.; Hanlon, Edward A.

Here, organic matter is a complex material that represents the long-term decay products from plants and other organisms in the soil. When organic matter is allowed to build up in a soil, the soil color at the surface usually turns a darker color, often with a red or brown hue. Typically in Florida mineral soils, organic matter content is quite low, within the range of 1 to 5%. However, in some soils that remain flooded for most of the year, organic matter can build up with time and actually become the soil. Such is the case for the organic soils,more » or histosols, found in southern Florida. These organic soils comprise much of the Water Conservation Areas, Everglades National Park (ENP), Big Cypress Basin, and the Everglades Agricultural Area (EAA). It is important to document organic matter accumulation in the Everglades to gauge the effectiveness of wetland creation and succession. For the EAA, the drained soils lose organic matter due to oxidation, so measurement of the organic matter content of these soils over the course of time indicates the oxidation potential and mineral incorporation from bedrock. Due to the wide diversity of soil types and methods of measuring soil organic matter, there is a need to devise a more universal method applicable to many types of histosols in south Florida. The intent of this publication is: 1.To describe a simple laboratory method for determining the organic matter content of the organic soils of southern Florida and demonstrate the importance of using this new procedure for improved accuracy and precision; 2.To utilize this updated laboratory procedure for field sites across Everglades wetlands and the EAA; and 3. To recommend this procedure be used by growers, state and federal agencies, and university and agency researchers dealing with the management of organic soils in southern Florida. Growers can use this improvement to organic matter measurement to keep lab testing costs low while getting a better, more quantitative estimate of organic carbon (organic matter) for decisions regarding pesticide applications and estimated contribution of nutrients released from the organic matter in their fields. Restoration efforts in the Everglades wetlands can be better documented with the lower cost, but now equally as useful, LOI test for organic carbon. Improvements to soil organic matter coupled with other measurements of biological health of the system can be documented with less work using the adjusted LOI calculations.« less

Neurotransmitters and pathophysiology of stroke: evidence for the release of glutamate and other transmitters/mediators in animals and humans.

PubMed

Dávalos, A; Shuaib, A; Wahlgren, N G

2000-11-01

There is convincing evidence from animal models of stroke that ischemia leads to an increase in the extracellular concentrations of excitatory amino acids (EAAs), especially glutamate. This accumulation of glutamate, which can reach up to 80 times normal at the centre of an ischemic lesion, is believed to be an important factor for the premature death of neurons that would otherwise survive the ischemic conditions and recover when flow is restored. In the technique of microdialysis, a small probe is inserted into the brain tissue. Fluid passing through the probe is separated from the brain parenchyma by a semipermeable membrane, through which substances released into the brain can diffuse. Analysis of the dialysate allows the nature and time course of release of substances, such as glutamate, to be determined. This technique has been used in patients undergoing resection of cerebral tumors, surgery for epilepsy, head trauma, subarachnoid hemorrhage, and cerebral infarction. Clamping or ligating the blood supply to the lobe about to be excised leads to a rapid accumulation in the dialysate of, among other substances, glutamate. Similar findings have been obtained during lobar resection for the treatment of severe epilepsy. Accumulations of glutamate to approximately 100 times the basal concentration have been found. There are also a few reports of microdialysis being performed in patients undergoing lobectomy after severe strokes or extracranial-intracranial bypass surgery. Again, high concentrations of glutamate have been reported. Another approach is to examine the blood and cerebrospinal fluid (CSF) for traces of EAAs. High concentrations of glutamate have been found in the blood and CSF within 24 hours of the onset of stroke. In animal models, plasma concentrations of glutamate begin to rise some 4 to 6 hours after middle cerebral artery (MCA) occlusions, reaching a peak at about 8 to 24 hours. Similarly, when glutamate is injected into the CSF of rats, there is a lag of approximately 4 hours before the concentration of glutamate in the blood rises. Therefore, it may be possible to detect the ongoing release of glutamate into the brain as a result of cerebral ischemia, which may aid in the selection of the most appropriate treatment. The results of microdialysis and plasma EAA analyses suggest that excitotoxic damage can occur over many hours. This implies that effective neuroprotectant strategies could provide clinical benefits over similarly prolonged periods.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review.

PubMed

Díaz-Delgado, Josué; Pool, Roy; Hoppes, Sharman; Cerezo, Argine; Quesada-Canales, Óscar; Stoica, George

2017-05-18

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies.

'Away Days' in multi-centre randomised controlled trials: a questionnaire survey of their use and a case study on the effect of one Away Day on patient recruitment.

PubMed

Jefferson, Laura; Cook, Liz; Keding, Ada; Brealey, Stephen; Handoll, Helen; Rangan, Amar

2015-11-06

'Away Days' (trial promotion and training events for trial site personnel) are a well-established method used by trialists to encourage engagement of research sites in the recruitment of patients to multi-centre randomised controlled trials (RCTs). We explored the use of Away Days in multi-centre RCTs and analysed the effect on patient recruitment in a case study. Members of the United Kingdom Trial Managers' Network were surveyed in June 2013 to investigate their experiences in the design and conduct of Away Days in RCTs. We used data from a multi-centre pragmatic surgical trial to explore the effects of an Away Day on the screening and recruitment of patients. A total of 94 people responded to the survey. The majority (78%), who confirmed had organised an Away Day previously, found them to be useful. This is despite their costs.. There was no evidence, however, from the analysis of data from a surgical trial that attendance at an Away Day increased the number of patients screened or recruited at participating sites. Although those responsible for managing RCTs in the UK tend to believe that trial Away Days are beneficial, evidence from a multi-centre surgical trial shows no improvement on a key indicator of trial success. This points to the need to carefully consider the aims, design and conduct of Away Days. Further more rigorous research nested within RCTs would be valuable to evaluate the design and conduct of Away Days. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Everglqades Mercury: Biogeochemistry, Modeling, and Possible Mitigation

NASA Astrophysics Data System (ADS)

Orem, W. H.

2015-12-01

In the 1980s high levels of methylmercury (MeHg) were found in fish and other biota in the Florida Everglades, prompting fish consumption advisories. As part of Everglades restoration efforts Federal and State Agencies initiated a research program to study the underlying causes of the MeHg contamination. As part of this multi-agency effort, the U.S. Geological Survey developed the ACME (Aquatic Cycling of Mercury in the Everglades) project to examine the underlying biogeochemical factors controlling MeHg production and bioaccumulation in the ecosystem. Field studies by ACME and others identified the many factors impacting MeHg production in the Everglades. Thes factors include: high mercury deposition, large wetland area with organic-rich anaerobic soil, high sulfate loading in surface runoff, circumneutral pH, and high dissolved organic matter (DOM) content. Florida Department of Environmental Protection efforts that reduced local mercury emissions by 90%, produced only a small reduction in mercury deposition on the Everglades, suggesting that most Hg deposited on the ecosystem originates from distant sources, and beyond the reach of regulators. ACME studies demonstrated that high sulfate loading to the Everglades comes from discharge of canal water originating in the Everglades Agricultural Area (EAA). The use of sulfur in agriculture and soil oxidation in the EAA have been shown to be the principal sources of the sulfate loading. Sulfate entering the ecosystem drives microbial sulfate reduction and MeHg production, but inhibition of MeHg production by sulfide (a byproduct of microbial sulfate reduction) makes the biogeochemistry complex. Laboratory microcosm and field mesocosm experiments by ACME helped define the complexity of the sulfur/MeHg biogeochemistry, and demonstrated the key role of dissolved organic matter in MeHg production. A conceptual model was developed that relates MeHg production to sulfate loading, DOM, and soil composition. This conceptual model was then used in the development of a mathematical model that relates how changes in sulfate loading affect MeHg production in the ecosystem. This model is currently being used to examine how limits on sulfate loading to the ecosystem could be used as a mitigation strategy to control MeHg production and levels of MeHg in Everglades biota.

Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics

PubMed Central

Turnbull, Pauline; Hawton, Keith; Geulayov, Galit; Waters, Keith; Ness, Jennifer; Townsend, Ellen; Khundakar, Kazem; Kapur, Nav

2016-01-01

Objective Rates of hospital presentation for self-harm in England were compared using different national and local data sources. Design The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. Setting Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). Primary outcome Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. Results The total number of self-harm episodes between 2010 and 2012 was 13 547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. Conclusions There was a consistent underestimation of presentations for self-harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self-harm. PMID:26883238

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

Paradoxes of Cosmic Flights

DTIC Science & Technology

1977-04-26

less energy than in tha case of a takeoff from the surface of the Sarth. during such a takeoff from the earth the rocket motor ought to accomplish a...the energy point of view to set the roc- ket in motion* at the point closest to the *arth, the perigee, or at the most distant from it,—the apogee...than 1/33 parts of tbat energy that is necjfjessary during initial braking at the nearest-to-the»eaa?tfl ’:■’■- :,’-::::-:’.. :’.-:--:’.--£. ■■K

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

PubMed Central

Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

2016-01-01

Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

Multicentric Evaluation of New Commercial Enzyme Immunoassays for the Detection of Immunoglobulin M and Total Antibodies against Hepatitis A Virus▿

PubMed Central

Arcangeletti, M. C.; Dussaix, E.; Ferraglia, F.; Roque-Afonso, A. M.; Graube, A.; Chezzi, C.

2011-01-01

A multicentric clinical study was conducted on representative sera from 1,738 European and U.S. subjects for the evaluation of new anti-hepatitis A virus enzyme immunoassays from Bio-Rad Laboratories. Comparison with reference DiaSorin S.p.A. tests confirmed the good performance of Bio-Rad assays (99.85% and 99.47% overall agreement in detecting total antibodies and IgM, respectively). PMID:21653739

CHOP chemotherapy for the treatment of canine multicentric T-cell lymphoma.

PubMed

Rebhun, R B; Kent, M S; Borrofka, S A E B; Frazier, S; Skorupski, K; Rodriguez, C O

2011-03-01

Dogs with multicentric T-cell lymphoma are commonly treated with CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone. The purpose of this study was to evaluate the use of CHOP chemotherapy for dogs with multicentric T-cell lymphoma. Identification of prognostic factors in this specific subset of dogs was of secondary interest. Twenty-three out of 24 dogs responded to CHOP chemotherapy and these dogs remained on the protocol for a median of 146 days. No variable was associated with progression free survival (PFS) including stage, substage, hypercalcemia or radiographic evidence of a cranial mediastinal mass. The median overall survival time (OST) for all dogs was 235 days. Dogs that were thrombocytopenic at presentation experienced a significantly longer OST (323 versus 212 days, P=0.01). © 2010 Blackwell Publishing Ltd.

Spontaneous multicentric soft tissue sarcoma in a captive African pygmy hedgehog (Atelerix albiventris): case report and literature review

PubMed Central

DÍAZ-DELGADO, Josué; POOL, Roy; HOPPES, Sharman; CEREZO, Argine; QUESADA-CANALES, Óscar; STOICA, George

2017-01-01

This report describes the clinical, macroscopic, histopathological and immunohistochemical features of a spontaneous multicentric extraskeletal sarcoma in an adult male African hedgehog (Atelerix albiventris). It also provides a succinct up-to-date review on neoplasia in this species. On autopsy examination, main gross findings included a moderately demarcated cranial mass and a multilobulated, caudal intra-abdominal mass. The cranial mass had perforated the underlying temporal and occipital bones and had extended into the cranial vault and was compressing the surface of the cerebellum and cerebrum. Histologic, histochemical and immunohistochemical analyses supported a diagnosis of multicentric poorly differentiated spindle cell sarcoma with fibrosarcomatous, storiform and myxoid foci. The high incidence of neoplasia and cross similarities renders the African hedgehog a suitable species for comparative pathology studies. PMID:28331115

Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort

PubMed Central

Gamundi, Maria José; Duch, Susana; Rios, Jose; Carballo, Miguel; Study Group, EMEIGG

2017-01-01

Introduction The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. Design Retrospective, observational, multicentre, cohort study. Material and Methods The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. Results 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. Conclusions The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment. PMID:29082038

Negative ions of p-nitroaniline: Photodetachment, collisions, and ab initio calculations

NASA Astrophysics Data System (ADS)

Smith, Byron H.; Buonaugurio, Angela; Chen, Jing; Collins, Evan; Bowen, Kit H.; Compton, Robert N.; Sommerfeld, Thomas

2013-06-01

The structures of parent anion, M-, and deprotonated molecule, [M-H]-, anions of the highly polar p-nitroaniline (pNA) molecule are studied experimentally and theoretically. Photoelectron spectroscopy (PES) of the parent anion is employed to estimate the adiabatic electron affinity (EAa = 0.75 ± 0.1 eV) and vertical detachment energy (VDE = 1.1 eV). These measured energies are in good agreement with computed values of 0.73 eV for the EAa and the range of 0.85 to 1.0 eV for the VDE at the EOM-CCSD/Aug-cc-pVTZ level. Collision induced dissociation (CID) of deprotonated pNA, [pNA - H]-, with argon yielded [pNA - H - NO]- (i.e., rearrangement to give loss of NO) with a threshold energy of 2.36 eV. Calculations of the energy difference between [pNA - H]- and [pNA - H - NO]- give 1.64 eV, allowing an estimate of a 0.72 eV activation barrier for the rearrangement reaction. Direct dissociation of [pNA - H]- yielding NO_2^ - occurs at a threshold energy of 3.80 eV, in good agreement with theory (between 3.39 eV and 4.30 eV). As a result of the exceedingly large dipole moment for pNA (6.2 Debye measured in acetone), we predict two dipole-bound states, one at ˜110 meV and an excited state at 2 meV. No dipole-bound states are observed in the photodetachment experiments due the pronounced mixing between states with dipole-bound and valence character similar to what has been observed in other nitro systems. For the same reason, dipole-bound states are expected to provide highly efficient "doorway states" for the formation of the pNA- valence anion, and these states should be observable as resonances in the reverse process, that is, in the photodetachment spectrum of pNA- near the photodetachment threshold.

Negative ions of p-nitroaniline: photodetachment, collisions, and ab initio calculations.

PubMed

Smith, Byron H; Buonaugurio, Angela; Chen, Jing; Collins, Evan; Bowen, Kit H; Compton, Robert N; Sommerfeld, Thomas

2013-06-21

The structures of parent anion, M(-), and deprotonated molecule, [M-H](-), anions of the highly polar p-nitroaniline (pNA) molecule are studied experimentally and theoretically. Photoelectron spectroscopy (PES) of the parent anion is employed to estimate the adiabatic electron affinity (EAa = 0.75 ± 0.1 eV) and vertical detachment energy (VDE = 1.1 eV). These measured energies are in good agreement with computed values of 0.73 eV for the EAa and the range of 0.85 to 1.0 eV for the VDE at the EOM-CCSD∕Aug-cc-pVTZ level. Collision induced dissociation (CID) of deprotonated pNA, [pNA - H](-), with argon yielded [pNA - H - NO](-) (i.e., rearrangement to give loss of NO) with a threshold energy of 2.36 eV. Calculations of the energy difference between [pNA - H](-) and [pNA - H - NO](-) give 1.64 eV, allowing an estimate of a 0.72 eV activation barrier for the rearrangement reaction. Direct dissociation of [pNA - H](-) yielding NO2(-) occurs at a threshold energy of 3.80 eV, in good agreement with theory (between 3.39 eV and 4.30 eV). As a result of the exceedingly large dipole moment for pNA (6.2 Debye measured in acetone), we predict two dipole-bound states, one at ~110 meV and an excited state at 2 meV. No dipole-bound states are observed in the photodetachment experiments due the pronounced mixing between states with dipole-bound and valence character similar to what has been observed in other nitro systems. For the same reason, dipole-bound states are expected to provide highly efficient "doorway states" for the formation of the pNA(-) valence anion, and these states should be observable as resonances in the reverse process, that is, in the photodetachment spectrum of pNA(-) near the photodetachment threshold.

Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein Synthesis following Resistance Exercise in Humans

PubMed Central

Jackman, Sarah R.; Witard, Oliver C.; Philp, Andrew; Wallis, Gareth A.; Baar, Keith; Tipton, Kevin D.

2017-01-01

The ingestion of intact protein or essential amino acids (EAA) stimulates mechanistic target of rapamycin complex-1 (mTORC1) signaling and muscle protein synthesis (MPS) following resistance exercise. The purpose of this study was to investigate the response of myofibrillar-MPS to ingestion of branched-chain amino acids (BCAAs) only (i.e., without concurrent ingestion of other EAA, intact protein, or other macronutrients) following resistance exercise in humans. Ten young (20.1 ± 1.3 years), resistance-trained men completed two trials, ingesting either 5.6 g BCAA or a placebo (PLA) drink immediately after resistance exercise. Myofibrillar-MPS was measured during exercise recovery with a primed, constant infusion of L-[ring13C6] phenylalanine and collection of muscle biopsies pre and 4 h-post drink ingestion. Blood samples were collected at time-points before and after drink ingestion. Western blotting was used to measure the phosphorylation status of mTORC1 signaling proteins in biopsies collected pre, 1-, and 4 h-post drink. The percentage increase from baseline in plasma leucine (300 ± 96%), isoleucine (300 ± 88%), and valine (144 ± 59%) concentrations peaked 0.5 h-post drink in BCAA. A greater phosphorylation status of S6K1Thr389 (P = 0.017) and PRAS40 (P = 0.037) was observed in BCAA than PLA at 1 h-post drink ingestion. Myofibrillar-MPS was 22% higher (P = 0.012) in BCAA (0.110 ± 0.009%/h) than PLA (0.090 ± 0.006%/h). Phenylalanine Ra was ~6% lower in BCAA (18.00 ± 4.31 μmol·kgBM−1) than PLA (21.75 ± 4.89 μmol·kgBM−1; P = 0.028) after drink ingestion. We conclude that ingesting BCAAs alone increases the post-exercise stimulation of myofibrillar-MPS and phosphorylation status mTORC1 signaling. PMID:28638350

Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma

PubMed Central

Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma'ayan, Avi; Nam, Do-Hyun

2016-01-01

We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naïve GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID:26863628

The NH2-terminus of substance P modulates NMDA-induced activity in the mouse spinal cord.

PubMed

Hornfeldt, C S; Sun, X; Larson, A A

1994-05-01

Excitatory amino acids (EAAs) and substance P are believed to transmit nociceptive information in the spinal cord. As substance P NH2-terminal fragments can modulate non-NMDA EAA-mediated activity, we examined the effects of substance P fragments to ascertain whether the COOH- or NH2-terminus of substance P modulates the actions of NMDA in the spinal cord. NMDA activity was measured by the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally in the mouse. The NMDA response was attenuated after pretreatment with either substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP-(1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30 min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting that the inhibitory effect of substance P is caused by the NH2-terminus. Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist, potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA, coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of NMDA, first inhibited but then potentiated responses to each challenge with NMDA. Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats.

PubMed

Markison, S; Thompson, B L; Smith, J C; Spector, A C

2000-05-01

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.

High Serum Essential Amino Acids as a Predictor of Skeletal Muscle Depletion in Patients With Cachexia and Advanced Gastrointestinal Cancers.

PubMed

Kitagawa, Moeko; Haji, Seiji; Amagai, Teruyoshi

2017-10-01

In recent years, the number of patients with cancer has increased. These patients are prone to sarcopenia as a result of the decrease in muscle mass and muscle weakness that occur in cancer cachexia. Amino Index Cancer Screening is carried out to evaluate cancer cachexia risk by examining amino acid concentration and analyzing amino acid balance. We conducted a retrospective chart review of consecutive patients with unresectable advanced gastrointestinal cancer (stage IV) receiving chemotherapy treatment (December 2012-September 2015) in an outpatient or in-hospital setting at our institution (N = 46). Data included characteristics, psoas muscle area per computed tomography, and biochemical blood test and serum amino acid profiles. Method 1: Comparison of biomarkers between 2 groups: psoas muscle index change rate (ΔPMI) decrease vs increase. Method 2.1: Correlation between ΔPMI and biomarkers. Method 2.2: Multiple regression of ΔPMI and biomarkers. EAA/TAA ratio (essential amino acids/total amino acids) in the decrease group was significantly higher than that in the increase group. Among all parameters, serum C-reactive protein (CRP), leucine, and isoleucine were negatively related to ΔPMI (correlation coefficients = -0.604, -0.540, -0.518; P = .004, .011, .016, respectively). On multiple regression analysis, serum CRP value was strongly related to ΔPMI ( r 2 = 0.452, β = -0.672, P = .001). Higher serum EAA/TAA ratio and CRP were associated with depletion in psoas muscle area, which led to a diagnosis of sarcopenia, in patients with advanced gastrointestinal cancers. These parameters at baseline could be predictors of cancer cachexia.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

The changes in the biochemical compositions and enzymatic activities of rotifer (Brachionus plicatilis, Müller) and Artemia during the enrichment and starvation periods.

PubMed

Naz, Mehmet

2008-12-01

The changes in the biochemical compositions and enzymatic activities of rotifer (Brachionus plicatilis) and Artemia, enriched and stored at 4 degrees C temperature, were determined. The total starvation period was 16 h and samples were taken at the end of the 8th and 16th hours. In present study, the rotifer and nauplii catabolized a large proportion of the protein during the enrichment period. Lipid contents of both live preys increased during the enrichment period and decreased in nauplii and metanauplii throughout the starvation period but lipid content of the rotifer remained relatively constant during the starvation period. The changes observed in the amino acid compositions of Artemia and the rotifer were statistically significant (P < 0.05). The conspicuous decline the essential amino acid (EAA) and nonessential amino acid (NEAA) content of the rotifer was observed during the enrichment period. However, the essential amino acid (EAA) and nonessential amino acid (NEAA) contents of Artemia nauplii increased during the enrichment period. The unenriched and enriched rotifers contained more monounsaturated fatty acid (MUFAs) than polyunsaturated fatty acid (PUFAs) and saturated fatty acids (SFA). However, Artemia contained more PUFAs than MUFAs and SFA during the experimental period. A sharp increase in the amounts of docosahexaenoic acid (DHA) during the enrichment of the rotifer and Artemia nauplii was observed. However, the amount of DHA throughout the starvation period decreased in Artemia metanauplii but not in Artemia nauplii. Significant differences in tryptic, leucine aminopeptidase N (LAP), and alkaline phosphatase (AP) enzyme activities of Artemia and rotifer were observed during the enrichment and starvation period (P < 0.05). The digestive enzymes derived from live food to fish larvae provided the highest contribution at the end of the enrichment period. In conclusion, the results of the study provide important contributions to determine the most suitable live food offering time for marine fish larvae. Rotifer should be offered to fish larvae at the end of the enrichment period, Artemia nauplii just after hatching and before being stored at 4 degrees C, and Artemia metanauplii at the end of the enrichment and throughout the starvation period.

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation

PubMed Central

Tanner, Ruth E; Brunker, Lucille B; Agergaard, Jakob; Barrows, Katherine M; Briggs, Robert A; Kwon, Oh Sung; Young, Laura M; Hopkins, Paul N; Volpi, Elena; Marcus, Robin L; LaStayo, Paul C; Drummond, Micah J

2015-01-01

Abstract Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults. Key points Five days of bed rest resulted in a reduction in leg lean mass and strength in older adults. After bed rest, older (but not younger) adults had reduced amino acid-induced anabolic sensitivity (blunted muscle protein synthesis; MPS) and enhanced markers associated with the ubiquitin proteasome and autophagy–lysosomal systems (increase in molecular markers related to muscle proteolysis). Younger adults did not lose leg lean mass (via DXA) after 5 days of bed rest despite blunted amino acid-induced mTORC1 signalling and increased skeletal muscle REDD1, REDD2 and MURF1 mRNA expression. Exercise rehabilitation restored bed rest-induced deficits in lean mass, strength, nutrient-induced protein anabolism (protein synthesis and mTORC1 signalling) and select muscle proteolytic markers in older adults. PMID:26173027

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Oxidative stress in dogs with multicentric lymphoma: Effect of chemotherapy on oxidative and antioxidant biomarkers.

PubMed

Bottari, Nathieli B; Munhoz, Thiago D; Torbitz, Vanessa D; Tonin, Alexandre A; Anai, Letícia A; Semolin, Lívia M S; Jark, Paulo C; Bollick, Yãnaí S; Moresco, Rafael N; França, Raqueli T; Lopes, Sonia T A; Stefani, Lenita M; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

2015-01-01

Lymphoma is one of the most common types of cancer in dogs, characterized by the proliferation of lymphoid cells. The treatment of this type of cancer is usually based on drugs with high toxicity, which can cause severe side effects. Therefore, the aim of this study was to measure the levels of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), and ferric reducing antioxidant power (FRAP) in dogs with multicentric lymphoma before and after chemotherapy. For this purpose, serum samples of 25 dogs diagnosed with multicentric lymphoma and 15 healthy dogs were used. The animals were exposed to CHOP chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisone) and serum samples were collected 5 weeks after treatment. High levels of TBARS, AOPP, and FRAP were observed in sera of dogs with multicentric lymphoma when compared to healthy dogs (P < 0.01), and even higher levels (TBARS and AOPP) were found after chemotherapy i.e. treatment exacerbated the oxidative stress levels. On the other hand, FRAP levels did not differ statistically between animals with lymphoma before and after treatment (P > 0.05). Exacerbated oxidative stress was observed in dogs with multicentric lymphoma Group II (Stage IV-V: involvement of lymph nodes and organs) compared to those in Group I (Stage I-III: only affected lymph nodes) of the disease, as well as the dogs with clinical signs and T immunophenotype. Another important result was observed after chemotherapy, where FRAP levels were higher in dogs that showed complete disease remission compared to animals with progressive disease. Therefore, dogs with lymphoma showed protein oxidation and lipid peroxidation, as well as increased total antioxidants before and after chemotherapy compared to the control group.

A double blind multicentre study of OM-8980 and auranofin in rheumatoid arthritis.

PubMed Central

Vischer, T L

1988-01-01

The therapeutic efficacy of the immunomodulator OM-8980 in rheumatoid arthritis was compared with that of auranofin, an oral gold salt, in a double blind, randomised multicentre study lasting six months. Seventy patients were treated with auranofin and 75 with OM-8980. The patients of both groups improved significantly at three and six months for all the clinical parameters observed: Ritchie index, number of swollen joints, morning stiffness, pain, grip strength, intake of non-steroidal anti-inflammatory drugs, and erythrocyte sedimentation rate. No serious side effects were observed in either group. The patients receiving auranofin had more adverse reactions, mainly affecting the gastrointestinal system. PMID:3041924

Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database

PubMed Central

Nestor, Sean M.; Rupsingh, Raul; Borrie, Michael; Smith, Matthew; Accomazzi, Vittorio; Wells, Jennie L.; Fogarty, Jennifer

2008-01-01

Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n = 152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an ε4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P = 0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between Apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies. PMID:18669512

Ethical issues: the multi-centre low-risk ethics/governance review process and AMOSS.

PubMed

Vaughan, Geraldine; Pollock, Wendy; Peek, Michael J; Knight, Marian; Ellwood, David; Homer, Caroline S; Pulver, Lisa Jackson; McLintock, Claire; Ho, Maria T; Sullivan, Elizabeth A

2012-04-01

The Australasian Maternity Outcomes Surveillance System (AMOSS) conducts surveillance and research of rare and serious conditions in pregnancy. This multi-centre population health study is considered low risk with minimal ethical impact. To describe the ethics/governance review pathway undertaken by AMOSS. Prospective, descriptive study during 2009-2011 of the governance/ethical review processes required to gain approval for Australian and New Zealand (ANZ) maternity units with more than 50 births per year (n = 303) to participate in AMOSS. Review processes ranged from a single application for 24 NZ sites, a single application for eligible hospitals in two Australian states, full Health Research Ethics Committee (HREC) applications for individual hospitals, through simple letters of support. As of September 2011, 46 full/expedited ethics applications, 131 site governance applications and 136 letters of support requests were made over 33 months, involving an estimated 3261 hours by AMOSS staff/investigators, and an associated resource burden by participating sites, to obtain approval to receive nonidentifiable data from 291 hospitals. The AMOSS research system provides an important resource to enhance knowledge of conditions that cause rare and serious maternal morbidity. Yet the highly variable ethical approval processes required to implement this study have been excessively repetitive and burdensome. This process jeopardises timely, efficient research project implementation, without corresponding benefits to research participants. The resource burden to establish research governance for AMOSS confirms the urgent need for the Harmonisation of Multi-centre Ethical Review (HoMER) to further streamline ethics/governance review processes for multi-centre research. © 2011 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology © 2011 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Differential effects of military training on fat-free mass and plasma amino acid adaptations in men and women.

PubMed

Margolis, Lee M; Pasiakos, Stefan M; Karl, J Philip; Rood, Jennifer C; Cable, Sonya J; Williams, Kelly W; Young, Andrew J; McClung, James P

2012-12-18

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT.

Differential Effects of Military Training on Fat-Free Mass and Plasma Amino Acid Adaptations in Men and Women

PubMed Central

Margolis, Lee M.; Pasiakos, Stefan M.; Karl, J. Philip; Rood, Jennifer C.; Cable, Sonya J.; Williams, Kelly W.; Young, Andrew J.; McClung, James P.

2012-01-01

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT. PMID:23250145

Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery.

PubMed

Nepogodiev, Dmitri; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Khatri, Chetan; Drake, Thomas M; Kong, Chia Yew; Mitchell, Harriet; Harrison, Ewen M; Fitzgerald, J Edward; Bhangu, Aneel

2015-07-20

Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III-V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A feasibility study investigating the acceptability and design of a multicentre randomised controlled trial of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contractures of the fingers (HAND-1): study protocol for a randomised controlled trial.

PubMed

Harrison, Eleanor; Tan, Wei; Mills, Nicola; Karantana, Alexia; Sprange, Kirsty; Duley, Lelia; Elliott, Daisy; Blazeby, Jane; Hollingworth, William; Montgomery, Alan A; Davis, Tim

2017-08-25

Dupuytren's contractures are fibrous cords under the skin of the palm of the hand. The contractures are painless but cause one or more fingers to curl into the palm, resulting in loss of function. Standard treatment within the NHS is surgery to remove (fasciectomy) or divide (fasciotomy) the contractures, and the treatment offered is frequently determined by surgeon preference. This study aims to determine the feasibility of conducting a large, multicentre randomised controlled trial to assess the clinical and cost-effectiveness of needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren's contracture. HAND-1 is a parallel, two-arm, multicentre, randomised feasibility trial. Eligible patients aged 18 years or over who have one or more fingers with a Dupuytren's contracture of more than 30° in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints, well-defined cord(s) causing contracture, and have not undergone previous surgery for Dupuytren's on the same hand will be randomised (1:1) to treatment with either needle fasciotomy or limited fasciectomy. Participants will be followed-up for up to 6 months post surgery. Feasibility outcomes include number of patients screened, consented and randomised, adherence with treatment, completion of follow-up and identification of an appropriate patient-reported outcome measure (PROM) to use as primary outcome for a main trial. Embedded qualitative research, incorporating a QuinteT Recruitment Intervention, will focus on understanding and optimising the recruitment process, and exploring patients' experiences of trial participation and the interventions. This study will assess whether a large multicentre trial comparing the clinical and cost-effectiveness of needle fasciotomy and limited fasciectomy for the treatment of Dupuytren's contractures is feasible, and if so will provide data to inform its design and successful conduct. International Standard Registered Clinical/soCial sTudy Number: ISRCTN11164292 . Registered on 28 August 2015.

A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

PubMed

Rigg, J R A

2016-07-01

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

EBV+ HHV-8+ Multicentric Castleman Disease With Plasmablastic Aggregates in an HIV+ Man: An Evolving Clinicopathologic Entity.

PubMed

Shivane, Aditya; Pearce, Amy; Khatib, Nadia; Smith, Mark E F

2018-06-01

We report a case of EBV+ and HHV-8+ multicentric Castleman disease with plasmablastic aggregates in an HIV-positive individual. A 41-year-old man presented in early 2015 with fevers, sweats, weight loss, intractable itching, and on subsequent testing was found to be HIV positive. Investigations showed cervical lymphadenopathy and splenomegaly. He was treated for HIV and his symptoms resolved. His symptoms recurred in January 2016, and a provisional diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left supraclavicular lymph node core biopsy was performed, which showed features of multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER) and HHV-8 positive. He responded well to rituximab treatment and remains well with no symptoms at recent follow-up.

Multi-Centrality Graph Spectral Decompositions and Their Application to Cyber Intrusion Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Pin-Yu; Choudhury, Sutanay; Hero, Alfred

Many modern datasets can be represented as graphs and hence spectral decompositions such as graph principal component analysis (PCA) can be useful. Distinct from previous graph decomposition approaches based on subspace projection of a single topological feature, e.g., the centered graph adjacency matrix (graph Laplacian), we propose spectral decomposition approaches to graph PCA and graph dictionary learning that integrate multiple features, including graph walk statistics, centrality measures and graph distances to reference nodes. In this paper we propose a new PCA method for single graph analysis, called multi-centrality graph PCA (MC-GPCA), and a new dictionary learning method for ensembles ofmore » graphs, called multi-centrality graph dictionary learning (MC-GDL), both based on spectral decomposition of multi-centrality matrices. As an application to cyber intrusion detection, MC-GPCA can be an effective indicator of anomalous connectivity pattern and MC-GDL can provide discriminative basis for attack classification.« less

Twelve-month short-term safety and visual-acuity results from a multicentre prospective study of epiretinal strontium-90 brachytherapy with bevacizumab for the treatment of subfoveal choroidal neovascularisation secondary to age-related macular degeneration.

PubMed

Avila, M P; Farah, M E; Santos, A; Duprat, J P; Woodward, B W; Nau, J

2009-03-01

This study evaluated the short-term safety and feasibility of epiretinal strontium-90 brachytherapy delivered concomitantly with intravitreal bevacizumab for the treatment of subfoveal CNV due to AMD for 12 months. A 3-year follow-up is planned. In this prospective, non-randomised, multicentre study, 34 treatment-naïve patients with predominantly classic, minimally classic and occult subfoveal CNV lesions received a single treatment with 24 Gy beta radiation (strontium-90) and two injections of the anti-VEGF antibody bevacizumab. Adverse events were observed. BCVA was measured using standard ETDRS vision charts. Twelve months after treatment, no radiation-associated adverse events were observed. In the intent-to-treat (ITT) population, 91% of patients lost <3 lines (15 ETDRS letters) of vision at 12 months, 68% improved or maintained their BCVA at 12 months, and 38% gained >/=3 lines. The mean change in BCVA observed at month 12 was a gain of 8.9 letters. The safety and efficacy of intraocular, epiretinal brachytherapy delivered concomitantly with anti-VEGF therapy for the treatment of subfoveal CNV secondary to AMD were promising in this small study population. Long-term safety will be assessed for 3 years. This regimen is being evaluated in a large, multicentre, phase III study.

Harmonization Process and Reliability Assessment of Anthropometric Measurements in the Elderly EXERNET Multi-Centre Study

PubMed Central

Gómez-Cabello, Alba; Vicente-Rodríguez, Germán; Albers, Ulrike; Mata, Esmeralda; Rodriguez-Marroyo, Jose A.; Olivares, Pedro R.; Gusi, Narcis; Villa, Gerardo; Aznar, Susana; Gonzalez-Gross, Marcela; Casajús, Jose A.; Ara, Ignacio

2012-01-01

Background The elderly EXERNET multi-centre study aims to collect normative anthropometric data for old functionally independent adults living in Spain. Purpose To describe the standardization process and reliability of the anthropometric measurements carried out in the pilot study and during the final workshop, examining both intra- and inter-rater errors for measurements. Materials and Methods A total of 98 elderly from five different regions participated in the intra-rater error assessment, and 10 different seniors living in the city of Toledo (Spain) participated in the inter-rater assessment. We examined both intra- and inter-rater errors for heights and circumferences. Results For height, intra-rater technical errors of measurement (TEMs) were smaller than 0.25 cm. For circumferences and knee height, TEMs were smaller than 1 cm, except for waist circumference in the city of Cáceres. Reliability for heights and circumferences was greater than 98% in all cases. Inter-rater TEMs were 0.61 cm for height, 0.75 cm for knee-height and ranged between 2.70 and 3.09 cm for the circumferences measured. Inter-rater reliabilities for anthropometric measurements were always higher than 90%. Conclusion The harmonization process, including the workshop and pilot study, guarantee the quality of the anthropometric measurements in the elderly EXERNET multi-centre study. High reliability and low TEM may be expected when assessing anthropometry in elderly population. PMID:22860013

Montelukast (Singulair) and Pregnancy

MedlinePlus

... 2009. Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes Eur J Clin Pharmacol. ... Conditions of Use Site By: Marketing and Advertising Design Group

Nutritional Value of Commercial Protein-Rich Plant Products.

PubMed

Mattila, Pirjo; Mäkinen, Sari; Eurola, Merja; Jalava, Taina; Pihlava, Juha-Matti; Hellström, Jarkko; Pihlanto, Anne

2018-06-01

The goal of this work was to analyze nutritional value of various minimally processed commercial products of plant protein sources such as faba bean (Vicia faba), lupin (Lupinus angustifolius), rapeseed press cake (Brassica rapa/napus subsp. Oleifera), flaxseed (Linum usitatissimum), oil hemp seed (Cannabis sativa), buckwheat (Fagopyrum esculentum), and quinoa (Chenopodium quinoa). Basic composition and various nutritional components like amino acids, sugars, minerals, and dietary fiber were determined. Nearly all the samples studied could be considered as good sources of essential amino acids, minerals and dietary fiber. The highest content of crude protein (over 30 g/100 g DW) was found in faba bean, blue lupin and rapeseed press cake. The total amount of essential amino acids (EAA) ranged from 25.8 g/16 g N in oil hemp hulls to 41.5 g/16 g N in pearled quinoa. All the samples studied have a nutritionally favorable composition with significant health benefit potential. Processing (dehulling or pearling) affected greatly to the contents of analyzed nutrients.

Authorship issues in multi-centre clinical trials: the importance of making an authorship contract.

PubMed

Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian; Vinther, Siri

2015-02-01

Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them to qualify for authorship as defined by the International Committee of Medical Journal Editors. Therefore, rules for authorship in multi-centre trials are strongly recommended. We propose two contracts to prevent conflicts regarding authorship; both are freely available for use without pay but with reference to the original source.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective.

PubMed

Ezzat, Hanna; Ross, Sue; von Dadelszen, Peter; Morris, Tara; Liston, Robert; Magee, Laura A

2010-07-30

For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology.

PubMed

Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne; Albertsen, Birgitte K; Frisk, Tony; Tedgård, Ulf; Jónsson, Ólafur G; Pruunsild, Kaie; Gretenkort Andersson, Nadine; Winther Gunnes, Maria; Saulyte Trakymiene, Sonata; Frandsen, Thomas; Heyman, Mats; Ruud, Ellen; Helgestad, Jon

2015-02-01

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication. © 2014 John Wiley & Sons Ltd.

Early 2016/17 vaccine effectiveness estimates against influenza A(H3N2): I-MOVE multicentre case control studies at primary care and hospital levels in Europe

PubMed Central

Kissling, Esther; Rondy, Marc

2017-01-01

We measured early 2016/17 season influenza vaccine effectiveness (IVE) against influenza A(H3N2) in Europe using multicentre case control studies at primary care and hospital levels. IVE at primary care level was 44.1%, 46.9% and 23.4% among 0–14, 15–64 and ≥ 65 year-olds, and 25.7% in the influenza vaccination target group. At hospital level, IVE was 2.5%, 7.9% and 2.4% among ≥ 65, 65–79 and ≥ 80 year-olds. As in previous seasons, we observed suboptimal IVE against influenza A(H3N2). PMID:28230524

Efficient, quality-assured data capture in operational research through innovative use of open-access technology

PubMed Central

Naik, B.; Guddemane, D. K.; Bhat, P.; Wilson, N.; Sreenivas, A. N.; Lauritsen, J. M.; Rieder, H. L.

2013-01-01

Ensuring quality of data during electronic data capture has been one of the most neglected components of operational research. Multicentre studies are also challenged with issues about logistics of travel, training, supervision, monitoring and troubleshooting support. Allocating resources to these issues can pose a significant bottleneck for operational research in resource-limited settings. In this article, we describe an innovative and efficient way of coordinating data capture in multicentre operational research using a combination of three open access technologies—EpiData for data capture, Dropbox for sharing files and TeamViewer for providing remote support. PMID:26392997

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial

PubMed Central

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-01-01

Objectives Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. Methods/design This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. Ethics and dissemination This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. Trial registration number NCT02886156; pre-results. PMID:28550021

Salmeterol versus slow-release theophylline combined with ketotifen in nocturnal asthma: a multicentre trial. French Multicentre Study Group.

PubMed

Muir, J F; Bertin, L; Georges, D

1992-11-01

We wished to assess the efficacy of inhaled salmeterol (SML; 50 micrograms b.i.d.) compared to a combination of slow-release theophylline and ketotifen p.o. (TK; T 300 mg+K 1 mg b.i.d.) for the treatment of nocturnal asthma. Ninety six patients with nocturnal asthma, (forced expiratory volume in one second (FEV1) 60-90% of predicted value, reversibility > or = 15%, at least two nocturnal awakenings per week) were eligible for a multicentre, double-blind, double-dummy cross-over study (14-day run-in, two successive 28-day treatment periods). Efficacy was assessed as success/failure, success being defined as the complete disappearance of nocturnal symptoms/awakening during the last week of each treatment period. There was a statistically significant difference between SML and TK for this criterion: 46% and 39% success with SML during periods I (first 28-day period) and II (following the cross-over), compared to only 15% and 26% with TK, respectively (p < 0.01). SML was also significantly better for the other criteria (lung function, rescue salbutamol intake during day and night). Side-effects were five times less frequent in SML-treated patients (p < 0.004). Efficacy and tolerance of SML were obviously far better than those of TK in patients with nocturnal asthma.

[Role of Institutional Review Boards for multi-centre studies in national health services research - a cross-sectional study of the effort to obtain secondary ethical approvals for the DACAPO study].

PubMed

Blecha, Sebastian; Thomann-Hackner, Kathrin; Brandstetter, Susanne; Dodoo-Schittko, Frank; Seboek, Philipp; Apfelbacher, Christian; Graf, Bernhard M; Bein, Thomas

2015-09-01

Health services research (HSR) is of fundamental importance for the continuous improvement of preventive, diagnostic or therapeutic measures. The conduct of multi-centre HSR studies requires that ethical approval by Institutional review boards (IRB's) is obtained. We documented the effort, the complexity and the man power necessary to obtain secondary ethical approval for a national HSR in Germany ("Surviving the Acute Respiratory Distress Syndrome" [DACAPO-study]). Having obtained a primary ethical approval by the IRB of Regensburg University, the time, correspondence, necessity for amendments, corrections, or additional costs by 34 IRB's for 64 participating study centers was documented. The complete obtainment was found to be time consuming and associated with a high workload and man power. A time span of seven month was needed to receive votes from all IRB's. The median time span was 25,5 days (25 %/75 % percentile 13 and 42 days, respectively). Requirements in terms of corrections or amendments were inhomogeneous and frequent changes were necessary. There were additional fees for secondary votes of 4328,40 €. Total costs for the study center Regensburg were 21.193,40 € (2,6 % of the grant volume). Obtaining all ethical approvals for a multi-centre observational HSR study in Germany is complex and time consuming. Various and inhomogeneous formalities may delay the plan and realization of HSR. A Homogenization and simplification of the procedure of ethics votes should be discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results.

PubMed

Hurtado-Chong, Anahí; Joeris, Alexander; Hess, Denise; Blauth, Michael

2017-07-12

A considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available. Selection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process. Out of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites. The results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies. ClinicalTrials.gov: NCT02297581. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Ex post facto assessment of diffusion tensor imaging metrics from different MRI protocols: preparing for multicentre studies in ALS.

PubMed

Rosskopf, Johannes; Müller, Hans-Peter; Dreyhaupt, Jens; Gorges, Martin; Ludolph, Albert C; Kassubek, Jan

2015-03-01

Diffusion tensor imaging (DTI) for assessing ALS-associated white matter alterations has still not reached the level of a neuroimaging biomarker. Since large-scale multicentre DTI studies in ALS may be hampered by differences in scanning protocols, an approach for pooling of DTI data acquired with different protocols was investigated. Three hundred and nine datasets from 170 ALS patients and 139 controls were collected ex post facto from a monocentric database reflecting different scanning protocols. A 3D correction algorithm was introduced for a combined analysis of DTI metrics despite different acquisition protocols, with the focus on the CST as the tract correlate of ALS neuropathological stage 1. A homogenous set of data was obtained by application of 3D correction matrices. Results showed that a fractional anisotropy (FA) threshold of 0.41 could be defined to discriminate ALS patients from controls (sensitivity/specificity, 74%/72%). For the remaining test sample, sensitivity/specificity values of 68%/74% were obtained. In conclusion, the objective was to merge data recorded with different DTI protocols with 3D correction matrices for analyses at group level. These post processing tools might facilitate analysis of large study samples in a multicentre setting for DTI analysis at group level to aid in establishing DTI as a non-invasive biomarker for ALS.

Painful bone metastasis in elderly treated with radiation therapy: Single- or multiple-fraction regimen? A multicentre retrospective observational analysis.

PubMed

Falivene, S; Pezzulla, D; Di Franco, R; Giugliano, F M; Esposito, E; Scoglio, C; Amato, B; Borzillo, V; D'Aiuto, M; Muto, P

2017-02-01

Bone metastases are a frequent complication of advanced oncologic disease. Pain associated to bone metastasis is a major cause of morbidity in cancer patients, especially in elderly. The aim of this multicentric retrospective observational study is to evaluate the efficacy of different schedules of radiation therapy in elderly patients in terms of pain relief. 206 patients over the age of 60 were enrolled in 1 year time for a multicentre retrospective observational study. Patients were treated with palliative purposes for painful bone metastases. Pain intensity difference (PID) was found in 72% of patients. Reported PID was statistically significant for p < 0.01. Pain intensity measured by a point numeric rating scale was statistically significant reduced for p < 0.05 by one-fraction regimen compared to other two regimens. In recent years, numerous studies have evaluated the most appropriate regimen of fractionation in individual cases, despite this, a consensus about the best schedule is still debated. On our analysis, single-fractionation scheme (8 Gy) confirmed to be statistical significant effective in providing pain reduction due to bone metastases. Radiation therapy provides significant pain relief of symptomatic bone metastases, but appropriate radiotherapy scheduled is needed in order to get significant response to treatment. Multidisciplinary approach is warranted to value the balance between the therapeutic objectives and the patient quality of life.

WebBioBank: a new platform for integrating clinical forms and shared neurosignal analyses to support multi-centre studies in Parkinson's Disease.

PubMed

Rossi, Elena; Rosa, Manuela; Rossi, Lorenzo; Priori, Alberto; Marceglia, Sara

2014-12-01

The web-based systems available for multi-centre clinical trials do not combine clinical data collection (Electronic Health Records, EHRs) with signal processing storage and analysis tools. However, in pathophysiological research, the correlation between clinical data and signals is crucial for uncovering the underlying neurophysiological mechanisms. A specific example is the investigation of the mechanisms of action for Deep Brain Stimulation (DBS) used for Parkinson's Disease (PD); the neurosignals recorded from the DBS target structure and clinical data must be investigated. The aim of this study is the development and testing of a new system dedicated to a multi-centre study of Parkinson's Disease that integrates biosignal analysis tools and data collection in a shared and secure environment. We designed a web-based platform (WebBioBank) for managing the clinical data and biosignals of PD patients treated with DBS in different clinical research centres. Homogeneous data collection was ensured in the different centres (Operative Units, OUs). The anonymity of the data was preserved using unique identifiers associated with patients (ID BAC). The patients' personal details and their equivalent ID BACs were archived inside the corresponding OU and were not uploaded on the web-based platform; data sharing occurred using the ID BACs. The system allowed researchers to upload different signal processing functions (in a .dll extension) onto the web-based platform and to combine them to define dedicated algorithms. Four clinical research centres used WebBioBank for 1year. The clinical data from 58 patients treated using DBS were managed, and 186 biosignals were uploaded and classified into 4 categories based on the treatment (pharmacological and/or electrical). The user's satisfaction mean score exceeded the satisfaction threshold. WebBioBank enabled anonymous data sharing for a clinical study conducted at multiple centres and demonstrated the capabilities of the signal processing chain configuration as well as its effectiveness and efficiency for integrating the neurophysiological results with clinical data in multi-centre studies, which will allow the future collection of homogeneous data in large cohorts of patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Multicentre imaging measurements for oncology and in the brain

PubMed Central

Tofts, P S; Collins, D J

2011-01-01

Multicentre imaging studies of brain tumours (and other tumour and brain studies) can enable a large group of patients to be studied, yet they present challenging technical problems. Differences between centres can be characterised, understood and minimised by use of phantoms (test objects) and normal control subjects. Normal white matter forms an excellent standard for some MRI parameters (e.g. diffusion or magnetisation transfer) because the normal biological range is low (<2–3%) and the measurements will reflect this, provided the acquisition sequence is controlled. MR phantoms have benefits and they are necessary for some parameters (e.g. tumour volume). Techniques for temperature monitoring and control are given. In a multicentre study or treatment trial, between-centre variation should be minimised. In a cross-sectional study, all groups should be represented at each centre and the effect of centre added as a covariate in the statistical analysis. In a serial study of disease progression or treatment effect, individual patients should receive all of their scans at the same centre; the power is then limited by the within-subject reproducibility. Sources of variation that are generic to any imaging method and analysis parameters include MR sequence mismatch, B1 errors, CT effective tube potential, region of interest generation and segmentation procedure. Specific tissue parameters are analysed in detail to identify the major sources of variation and the most appropriate phantoms or normal studies. These include dynamic contrast-enhanced and dynamic susceptibility contrast gadolinium imaging, T1, diffusion, magnetisation transfer, spectroscopy, tumour volume, arterial spin labelling and CT perfusion. PMID:22433831

Development of a web-based register for the Dutch national study on biologicals in JIA: www.ABC-register.nl.

PubMed

Prince, F H M; Ferket, I S; Kamphuis, S; Armbrust, W; Ten Cate, R; Hoppenreijs, E P A H; Koopman-Keemink, Y; van Rossum, M A J; van Santen-Hoeufft, M; Twilt, M; van Suijlekom-Smit, L W A

2008-09-01

Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study. We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data. The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved. By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

International Collaboration Enhances Cancer Screening Efforts

Cancer.gov

CGH is working with the International Agency for Research on CancerExit Disclaimer (IARC) and the Pan American Health Organization (PAHO) on the ESTAMPA Study, a multi-centric study of cervical cancer screening and triage with HPV testing.

Ethics review as a component of institutional approval for a multicentre continuous quality improvement project: the investigator's perspective

PubMed Central

2010-01-01

Background For ethical approval of a multicentre study in Canada, investigators must apply separately to individual Research Ethics Boards (REBs). In principle, the protection of human research subjects is of utmost importance. However, in practice, the process of multicentre ethics review can be time consuming and costly, requiring duplication of effort for researchers and REBs. We used our experience with ethical review of The Canadian Perinatal Network (CPN), to gain insight into the Canadian system. Methods The applications forms of 16 different REBs were abstracted for a list of standardized items. The application process across sites was compared. Correspondence between the REB and the investigators was documented in order to construct a timeline to approval, identify the specific issues raised by each board, and describe how they were resolved. Results Each REB had a different application form. Most (n = 9) had a two or three step application process. Overall, it took a median of 31 days (range 2-174 days) to receive an initial response from the REB. Approval took a median of 42 days (range 4-443 days). Privacy and consent were the two major issues raised. Several additional minor or administrative issues were raised which delayed approval. Conclusions For CPN, the Canadian REB process of ethical review proved challenging. REBs acted independently and without unified application forms or submission procedures. We call for a critical examination of the ethical, privacy and institutional review processes in Canada, to determine the best way to undertake multicentre review. PMID:20673343

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

PubMed

Omitola, Olufemi Gbenga; Soyele, Olujide Oladele; Sigbeku, Opeyemi; Okoh, Dickson; Akinshipo, Abdulwarith Olaitan; Butali, Azeez; Adeola, Henry Ademola

2017-01-01

Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa. In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL). Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 th and 7 th decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071). A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.

Local epidemiology and resistance profiles in acute uncomplicated cystitis (AUC) in women: a prospective cohort study in an urban urological ambulatory setting.

PubMed

Seitz, Michael; Stief, Christian; Waidelich, Raphaela

2017-10-16

Acute uncomplicated cystitis (AUC) is a common ailment in the urological setting. Guidelines for urinary tract infections are based on large-scale multi-centre, epidemiological and international studies. The objective of this observational study was to establish whether the results of a multi-centre study on the resistance profile of Escherichia coli (E. coli) in patients with AUC could be directly applied to an urological practice in a major European city or whether there are divergences in the resistance profile. An observational study was applied prospectively to 502 patients with AUC between January 2015 and January 2017). Personal data were anonymised. Exclusion criteria were the patient's age (<18) and treatment with an antibiotic in the week preceding examination. The average age was 32 (range 18-56). The most commonly detected bacteria was E. coli with 86%, followed by Enterococcus faecalis with 10% and Klebsiella pneumoniae with 4%. Resistance tests showed E. coli to be highly sensitive to fosfomycin (99.2%), nitrofurantoin (98.1%) and cefpodoxime (92.9%). E. coli exhibited resistance to ciprofloxacin (CIP) in 15.1%, to trimethoprim/sulfamethoxazole (TRS) in 25.2% and to amoxicillin/clavulanic acid (AMC) in 34% of cases. The comparison between data from this study and data from a multi-centre European (ECO-SENSI, ECO-SENSII and the 2014 update) showed relatively good sensitivity rates for fosfomycin and nitrofurantoin but significant differences in respect of resistance levels to TRS, CIP and AMC. AUC should therefore only be treated with TRS, CIP and AMC after a susceptibility test has been carried out.

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Occupational exposure to organic solvents during paint stripping and painting operations in the aeronautical industry.

PubMed

Vincent, R; Poirot, P; Subra, I; Rieger, B; Cicolella, A

1994-01-01

The exposure of workers to methylene chloride and phenol in an aeronautical workshop was measured during stripping of paint from a Boeing B 747. Methylene chloride exposure was measured during two work days by personal air sampling, while area sampling was used for phenol. During paint stripping operations, methylene chloride air concentrations ranged from 299.2 mg/m3 (83.1 ppm) to 1888.9 mg/m3 (524.7 ppm). The exposures to methylene chloride calculated for an 8-h work day ranged from 86 mg/m3 (23.9 ppm) to 1239.5 mg/m3 (344.3 ppm). In another aeronautical workshop, exposure to organic solvents, especially ethylene glycol monoethylether acetate (EGEEA), was controlled during the painting of an Airbus A 320. The external exposure to solvents and EGEEA was measured by means of individual air sampling. The estimation of internal exposure to EGEEA was made by measuring its urinary metabolite, ethoxyacetic acid (EAA). Both measurements were made during the course of 3 days. The biological samples were taken pre- and post-shift. During painting operations, methyl ethyl ketone, ethyl acetate, n-butyl alcohol, methyl isobutyl ketone, toluene, n-butyl acetate, ethylbenzene, xylenes and EGEEA were detected in working atmospheres. For these solvents, air concentrations ranged from 0.1 ppm to 69.1 ppm. EGEEA concentrations ranged from 29.2 mg/m3 (5.4 ppm) to 150.1 mg/m3 (27.8 ppm). For biological samples, the average concentrations of EAA were 108.4 mg/g creatinine in pre-shift and 139.4 mg/g creatinine in post-shift samples. Despite the fact that workers wore protective respiratory equipment during paint spraying operations, EEA urinary concentrations are high and suggest that percutaneous uptake is the main route of exposure for EGEEA.(ABSTRACT TRUNCATED AT 250 WORDS)

Effective translation of current dietary guidance: understanding and communicating the concepts of minimal and optimal levels of dietary protein.

PubMed

Rodriguez, Nancy R; Miller, Sharon L

2015-04-29

Dietitians and health care providers have critical roles in the translation of the dietary guidance to practice. The protein content of diets for adults can be based on the Recommended Dietary Allowance (RDA) of 0.80 g/kg per day. Alternatively, the most recent Dietary Reference Intakes (DRIs) for macronutrients reflect expanded guidance for assessing protein needs and consider the relative relation of absolute amounts of protein, carbohydrate, and fat to total energy intake in the context of chronic disease prevention. The Acceptable Macronutrient Distribution Range (AMDR) reflects the interrelation between the macronutrients and affords dietitians and clinicians additional flexibility in diet planning. Accounting for the caloric value of RDAs for carbohydrate and fat, "flexible calories" emerge as an opportunity to create varied eating plans that provide for protein intakes in excess of the RDA but within the AMDR. Protein Summit 2.0 highlighted the growing body of scientific evidence documenting the benefits of higher protein intakes at amounts approximating twice the RDA, which include promotion of healthy body weight and preservation of lean body mass and functional ability with age. The essential amino acid (EAA) density of a food also emerged as a novel concept analogous to "nutrient density," which can enable the practitioner to calculate the caloric cost associated with a specific protein source to attain the daily requirement of EAAs to accomplish various health outcomes because these indispensable nutrients have a significant role in protein utilization and metabolic regulation. Tailoring recommendations unique to an individual's varying goals and needs remains a challenge. However, flexibility within the application of DRIs to include consideration of the AMDR provides a sound framework to guide practitioners in effective translation of current dietary guidance with a specific regard for the documented benefits of higher protein intakes. © 2015 American Society for Nutrition.

Quantifying Trophic Interactions and Carbon Flow in Louisiana Salt Marshes Using Multiple Biomarkers

NASA Astrophysics Data System (ADS)

Polito, M. J.; Lopez-Duarte, P. C.; Olin, J.; Johnson, J. J.; Able, K.; Martin, C. W.; Fodrie, J.; Hooper-Bui, L. M.; Taylor, S.; Stouffer, P.; Roberts, B. J.; Rabalais, N. N.; Jensen, O.

2017-12-01

Salt marshes are critical habitats for many species in the northern Gulf of Mexico. However, given their complex nature, quantifying trophic linkages and the flow of carbon through salt marsh food webs is challenging. This gap in our understanding of food web structure and function limits our ability to evaluate the impacts of natural and anthropogenic stressors on salt marsh ecosystems. For example, 2010 Deepwater Horizon (DWH) oil spill had the potential to alter trophic and energy pathways. Even so, our ability to evaluate its effects on Louisiana salt marsh food webs was limited by a poor basis for comparison of the pre-spill baseline food web. To be better equipped to measure significant alterations in salt marsh ecosystems in the future, we quantified trophic interactions at two marsh sites in Barataria Bay, LA in May and October of 2015. Trophic structure and carbon flow across 52 species of saltmarsh primary producers and consumers were examined through a combination of three approaches: bulk tissue stable isotope analysis (δ13C, δ15N, δ34S), dietary fatty acid analysis (FAA), and compound-specific stable isotope analysis of essential amino acids (δ13C EAA). Bulk stable isotope analysis indicated similar trophic diversity between sites and seasons with the use of aquatic resources increasing concomitantly with trophic level. FAA and δ13C EAA biomarkers revealed that marsh organisms were largely divided into two groups: those that primarily derive carbon from terrestrial C4 grasses, and those that predominately derive carbon from a combination of phytoplankton and benthic microalgal sources. Differences in trophic structure and carbon flow were minimal between seasons and sites that were variably impacted by the DWH spill. These data on salt marsh ecosystem structure will be useful to inform future injury assessments and restoration initiatives.

Cyclosporin treatment for rheumatoid arthritis: a placebo controlled, double blind, multicentre study.

PubMed Central

van Rijthoven, A W; Dijkmans, B A; Goei The, H S; Hermans, J; Montnor-Beckers, Z L; Jacobs, P C; Cats, A

1986-01-01

The efficacy and safety of cyclosporin for patients with rheumatoid arthritis (RA) were assessed in a six month double blind, placebo controlled, multicentre study. The initial dosage of the drug was 10 mg/kg daily for two months. There were many discontinuations in both the cyclosporin group (eight out of 17) and the placebo group (six out of 19). Of the patients who completed the six months of therapy, those who had received cyclosporin showed a significant improvement in the number of swollen joints, the Ritchie articular index, and pain at active movement and at rest, compared not only with their condition at the start of the study, but also with the end results of the placebo group. Major adverse reactions to the drug were gastrointestinal disturbances and nephrotoxicity, which were probably due to the relatively high dosages of cyclosporin given in combination with non-steroidal anti-inflammatory drugs. PMID:3532966

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial.

PubMed

Xu, Huajun; Wang, Hui; Guan, Jian; Yi, Hongliang; Qian, Yingjun; Zou, Jianyin; Xia, Yunyan; Fu, Yiqun; Li, Xinyi; Jiao, Xiao; Huang, Hengye; Dong, Pin; Yu, Ziwei; Yang, Jun; Xiang, Mingliang; Li, Jiping; Chen, Yanqing; Wang, Peihua; Sun, Yizhou; Li, Yuehua; Zheng, Xiaojian; Jia, Wei; Yin, Shankai

2017-05-25

Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment. This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months. This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences. NCT02886156; pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Appendectomy versus non-operative treatment for acute uncomplicated appendicitis in children: study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

PubMed Central

Eaton, Simon; Abbo, Olivier; Arnaud, Alexis P; Beaudin, Marianne; Brindle, Mary; Bütter, Andreana; Davies, Dafydd; Jancelewicz, Tim; Johnson, Kathy; Keijzer, Richard; Lapidus-Krol, Eveline; Offringa, Martin; Piché, Nelson; Rintala, Risto; Skarsgard, Erik; Svensson, Jan F; Ungar, Wendy J; Wester, Tomas; Willan, Andrew R; Zani, Augusto; St Peter, Shawn D; Pierro, Agostino

2017-01-01

Background Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed. Methods Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5–16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children. Discussion The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies. Trial registration number clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016. PMID:29637088

Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.

PubMed

Wielpütz, Mark O; von Stackelberg, Oyunbileg; Stahl, Mirjam; Jobst, Bertram J; Eichinger, Monika; Puderbach, Michael U; Nährlich, Lutz; Barth, Sandra; Schneider, Christian; Kopp, Matthias V; Ricklefs, Isabell; Buchholz, Michael; Tümmler, Burkhard; Dopfer, Christian; Vogel-Claussen, Jens; Kauczor, Hans-Ulrich; Mall, Marcus A

2018-05-24

A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0-6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43-0.50, p < 0.01). Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Risk Analysis in Support of the Chemical Stockpile Disposal Program (CSDP). Volume 2. Consequence Data

DTIC Science & Technology

1987-12-17

OO O~oO~o OQOQCoOQOO 0000000000 UI z 00.00000000 0 0 0 0 0 0 0 0 0 0 0 0 U- (11KW f1 0Z =. -c OQ OO OO O OO O OO O OO O OO O OOIn O-WO 0 0 00 0 0 0 0...I.-.Oc.eaa aL ac ca ac aa ec a - acu~~~~~~~~~~~~~ .*..**-w aaca a8ac c e c acca ~~~~~~~~C a a9 a a ! a! a9 an aaacaaca aa aao ecaaaa z " .- C; Va ~cc a

Reference values for voluntary and stimulated single-fibre EMG using concentric needle electrodes: a multicentre prospective study.

PubMed

Kokubun, Norito; Sonoo, Masahiro; Imai, Tomihiro; Arimura, Yumiko; Kuwabara, Satoshi; Komori, Tetsuo; Kobayashi, Masahito; Nagashima, Takahide; Hatanaka, Yuki; Tsuda, Emiko; Misawa, Sonoko; Abe, Tatsuya; Arimura, Kimiyoshi

2012-03-01

The aim of this study is to establish reference values for single-fibre electromyography (SFEMG) using concentric needles in a prospective, multicentre study. Voluntary or stimulated SFEMG at the extensor digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a total of 69 normal subjects below the age of 60years at six Japanese institutes. The cut-off values for mean consecutive difference (MCD) of individual potentials were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper 10th percentile MCD value for individual subjects. The cut-off values for individual MCD (+2.5 SD) were 56.8μs for EDC-V (voluntary SFEMG for EDC), 58.8μs for EDC-S (stimulated SFEMG for EDC), 56.8μs for FRO-V (voluntary SFEMG for FRO) and 51.0μs for FRO-S (stimulated SFEMG for FRO). The false positive rates using these cut-off values were around 2%. The +2.5 SD and 95% prediction limit might be two optimal cut-off values, depending on the clinical question. The obtained reference values were larger than those reported previously using concentric needles, but might better coincide with conventional values. This is the first multicentre study reporting reference values for SFEMG using concentric needles. The way to determine cut-off values and the statistically correct definition of the percentile were discussed. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A Multi-centre Study to Assess the Long-term Performance of the Summit™ Hip in Primary Total Hip Replacement

ClinicalTrials.gov

2016-08-03

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

Multiple intraosseous hemangiomas-investigation and role of N-butylcyanoacrylate in management.

PubMed

Syal, Rajan; Tyagi, Isha; Goyal, Amit; Barai, Sukanto; Parihar, Anit

2007-05-01

Primary intraosseous hemangiomas are rare (0.7% of all osseous neoplasms), benign, slow-growing neoplasms. These lesions are usually solitary. We are reporting a case of multicentric intraosseous hemangiomas. Investigation, treatment options, and role of N-butylcyanoacrylate (NBCA) in management will be discussed. A 20-year-old man had multicentric intraosseous hemangiomas involving the skull bones, mandible, vertebra, pelvic bone, and tibial tuberosity. N-butylcyanoacrylate was used by direct puncture technique using a transosseous transcutaneous route to control profuse bleeding from the retromolar region. To the best of our knowledge, this is the first reported case with such extensive multicentric intraosseous hemangiomas. N-butylcyanoacrylate by direct puncture technique can be an effective method to devascularize and stabilize low-flow intraosseous vascular tumors. (c) 2007 Wiley Periodicals, Inc.

Physiological and morphological effects of high water tables on early growth of giant reed ( Arundo donax), elephant grass ( Pennisetum purpureum), energycane and sugarcane ( Saccharum spp.)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jennewein, Stephen Peter

Here, an increasing demand for renewable energy sources has spurred interest in high-biomass crops used for energy production. Species potentially well-suited for biofuel production in the seasonally wet organic Everglades Agricultural Area (EAA) of Florida include giant reed ( Arundo donax), elephant grass ( Pennisetum Purpureum), energycane ( Saccharum spp.), and sugarcane ( Saccharum spp.). The objectives in this study were to evaluate the role of fluctuating water tables on the morphology, physiology, and early season growth of these four genotypes. The candidate genotypes were grown in a greenhouse under three water table depths, defined by distance of the watermore » table from the soil surface: two constant water tables (-16 cm and -40 cm) along with a flood cycle (2 weeks of flood to the soil level followed by 2 weeks at -40 cm from the soil level). The genotypes included CP 89-2143 (sugarcane), L 79-1002 (energycane), Merkeron (elephant grass), and wild type (giant reed). The experiment was repeated for plant cane, first ratoon, and successive plant cane crop cycles. Reductions in dry matter yield were observed among genotypes subjected to the -40 cm drained, periodically flooded (40F) water table relative to the -40 cm constant (40C) or -16 cm constant (16C). Plant cane dry weights were reduced by 37% in giant reed, 52% in elephant grass, 42% in energycane, and 34% in sugarcane in the 40F compared to 40C water table treatments. Similarly, in the first ratoon crop dry weights were reduced by 29% in giant reed, 42% in elephant grass, 27% in energycane, and 62% in sugarcane. In plant cane and successive plant cane, average total dry weight was greatest for elephant grass whereas ratoon total dry weight was greatest for energycane. Genotype had more pronounced effects on physiological attributes than water table including the highest stomatal conductance and SPAD values in giant reed, and the highest stalk populations in elephant grass and energycane. Aerenchyma presence and volume increased under higher water tables with elephant grass having the greatest aerenchyma production. Because of the high yields and stalk populations in energycane and elephant grass for all crop stages seen in this study, these two genotypes show potential for bioenergy production in the EAA, but field trials are recommended to confirm this.« less

Compliance with clothing regulations and traffic flow in the operating room: a multi-centre study of staff discipline during surgical procedures.

PubMed

Loison, G; Troughton, R; Raymond, F; Lepelletier, D; Lucet, J-C; Avril, C; Birgand, G

2017-07-01

This multi-centre study assessed operating room (OR) staff compliance with clothing regulations and traffic flow during surgical procedures. Of 1615 surgical attires audited, 56% respected the eight clothing measures. Lack of compliance was mainly due to inappropriate wearing of jewellery (26%) and head coverage (25%). In 212 procedures observed, a median of five people [interquartile range (IQR) 4-6] were present at the time of incision. The median frequency of entries to/exits from the OR was 10.6/h (IQR 6-29) (range 0-93). Reasons for entries to/exits from the OR were mainly to obtain materials required in the OR (N=364, 44.5%). ORs with low compliance with clothing regulations tended to have higher traffic flows, although the difference was not significant (P=0.12). Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

[Antimicrobial susceptibility testing of anaerobic bacteria].

PubMed

García-Sánchez, José E; García-Sánchez, Enrique; García-García, María Inmaculada

2014-02-01

The anaerobic bacteria resistance to antibiotics is increasing, and even has appeared against the most active of those, like metronidazol and carbapenems. This fact forces to make and periodical sensibility tests -at least in the most aggressive and virulent species, in cases that they are isolated from life locations and in the absence of therapeutic response- to check the local sensibility and to establish suitable empiric therapies, all based on multicentric studies carried out in order to this or well to check the activity of new antibiotics. For the laboratory routine, the easiest sensibility method is the E-test/MIC evaluator. Another alternative is microdilution, that's only normalized for Bacteroides. There are preliminary facts that allow the use of disc diffusion method in some species of Bacteroides and Clostridium. For the temporal and multicentric studies, the procedure is dilution in agar plate, the reference method. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Mode of delivery and risk of intracranial haemorrhage in newborns with severe haemophilia A: a multicentre study in Gulf region.

PubMed

Nazir, H F; Al Lawati, T; Beshlawi, I; AlSharidah, S; Elshinawy, M; Alkasim, F; Khanani, M F; Tarawa, A; Al Subhi, T; Alrawas, A; Al Riyami, W; Al Kindi, S; Al Saadi, K; Al-Lamki, S; Wali, Y

2016-05-01

The optimum mode of delivery in a known carrier of a haemophilia A is still an issue of debate. This study was conducted to report a multicentre experience in Gulf Cooperation Council (GCC) on the incidence of intracranial haemorrhage (ICH) in newborns with severe haemophilia A delivered by different modalities. We have conducted a retrospective/prospective multicentre cohort study including a total of seven hospitals distributed in four GCC countries between 1998 and Jan 2015. A total of 163 patient with severe haemophilia A (factor VIII <1%) were enrolled in this study, age ranged between 2 weeks to 18 years. Most of the patients were born by spontaneous vaginal delivery (SVD) (131, 80.4%), whereas 26 patients (16%) were born by CS and only six patients were born by instrumental delivery (3.7%), five of them by vacuum and one was delivered using forceps. Five out of 163 patients developed ICH during the first 2 weeks of life (3.1%). Two of them were born by SVD (2/131; 1.5%) and two were born by instrumental delivery (2/6; 33.3%). Only one patient among those who were born by caesarean section developed ICH (1/26; 3.8%). Assisted vaginal delivery was associated with a significant risk of ICH, in comparison to SVD and CS (P = 0.0093). Normal vaginal delivery is still considered a safe journey through the birth canal for haemophilic newborns particularly in this area of the world. Larger prospective studies might be needed to define an evidence-based optimal mode of delivery for the haemophilia carrier expecting an affected child. © 2015 John Wiley & Sons Ltd.

Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases.

PubMed

Moreno, C; Cuesta-Herranz, J; Fernández-Távora, L; Alvarez-Cuesta, E

2004-04-01

The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17,526 administered doses, 17,368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.

A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

PubMed

Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

2016-06-01

Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

ESPGHAN 2012 Guidelines for Coeliac Disease Diagnosis: Validation Through a Retrospective Spanish Multicentric Study.

PubMed

Donat, Ester; Ramos, Jose M; Sánchez-Valverde, Félix; Moreno, Ana; Martinez, Maria-Jose; Leis, Rosaura; Peña-Quintana, Luis; Castillejo, Gemma; Fernández, Sonia; Garcia, Zuriñe; Ortigosa, Luis; Balmaseda, Elena; Marugán, José-Manuel; Eizaguirre, Francisco-Javier; Lorenzo, Helena; Barrio, Josefa; Ribes-Koninckx, Carmen

2016-02-01

A large retrospective multicentre study was conducted in Spain to evaluate the efficiency of the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) criteria for the diagnosis of coeliac disease (CD). The study protocol was approved by the ethics committee of Hospital Universitari i Politècnic La Fe (Valencia, Spain). The present study included 2177 children (ages 0.6-15.9 years) with small bowel biopsy (SBB) performed for diagnostic purposes (from 2000 to 2009) and with a minimum 2-year follow-up after biopsy. CD was diagnosed in 2126 patients (97.5%) and excluded in 51 (2.5%). Tissue transglutaminase antibodies (TG2A), anti-endomysial antibodies (EMA), and human leukocyte antigen (HLA) were reported in 751 patients, 640 symptomatic and 111 asymptomatic. TG2A levels >10 times the upper limit of normal, plus positive EMA and HLA DQ2 and/or DQ8 haplotypes, were found in 336 symptomatic patients, all of them with final diagnosis of CD. In 65 of 69 asymptomatic patients, 65 had confirmed CD and 4 did not have CD. According to the 2012 ESPGHAN guidelines, SBB may have been omitted in 52% of the symptomatic patients with CD with serologic and HLA available data. Gluten challenge was performed in 158 children, 75 of them <2 years at first biopsy. Only 1 patient in whom according to the new proposed diagnostic criteria gluten challenge would not have been mandatory did not relapse. Our results support the new ESPGHAN 2012 guidelines for diagnosis of CD can be safely used without the risk of overdiagnosis. A prospective multicentre study is needed to confirm our results.

[Multi-central controlled study on three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen].

PubMed

Zhou, Yun-feng; Wei, Yu-long; Zhang, Pu-lin; Gao, Shan; Ning, Guo-li; Zhang, Zhen-qiang; Hu, Bin; Wang, Dan-yi; Yan, Mei-rong; Liu, Wen-jun

2006-06-01

To make multi-central clinical evaluation for three-part massage therapy for treatment of insomnia of deficiency of both the heart and spleen. One hundred and sixty-six cases were randomly divided into a test group (n = 84) and a control group (n = 82). Multi-central, randomized and controlled methods were adopted. The test group were treated by the three-part massage therapy, i. e. acupoints at the head, abdomen and back were massaged, once each day; and the control group by oral administration of Guipi Pills [symbol: see text], 8 pills each time, thrice daily. The treatment was given for 15 consecutive days and then the therapeutic effects were observed. Sixty-seven cases were cured, 11 markedly effective, 3 effective, and 3 ineffective in the test group, and the corresponding figures were 10, 21, 29 and 22 in the control group with a very significant difference between the two groups (P< 0.001). The test group was superior to the control group in improvement for Pittsburgh Sleep Quality Index (PSQI), Sleepless Anxiety Scale (SAS) and Sleepless Depression Scale (SDS) (P < 0.001). The three-part massage therapy has definite therapeutic effect on insomnia of deficiency of both the heart and spleen with safety.

The foundation of NCVD PCI Registry: the Malaysia's first multi-centre interventional cardiology project.

PubMed

Liew, H B; Rosli, M A; Wan Azman, W A; Robaayah, Z; Sim, K H

2008-09-01

The National Cardiovascular Database for Percutaneous Coronary Intervention (NCVD PCI) Registry is the first multicentre interventional cardiology project, involving the main cardiac centres in the country. The ultimate goal of NCVD PCI is to provide a contemporary appraisal of PCI in Malaysia. This article introduces the foundation, the aims, methodology, database collection and preliminary results of the first six-month database.

Influence of magnetic field strength and image registration strategy on voxel-based morphometry in a study of Alzheimer's disease.

PubMed

Marchewka, Artur; Kherif, Ferath; Krueger, Gunnar; Grabowska, Anna; Frackowiak, Richard; Draganski, Bogdan

2014-05-01

Multi-centre data repositories like the Alzheimer's Disease Neuroimaging Initiative (ADNI) offer a unique research platform, but pose questions concerning comparability of results when using a range of imaging protocols and data processing algorithms. The variability is mainly due to the non-quantitative character of the widely used structural T1-weighted magnetic resonance (MR) images. Although the stability of the main effect of Alzheimer's disease (AD) on brain structure across platforms and field strength has been addressed in previous studies using multi-site MR images, there are only sparse empirically-based recommendations for processing and analysis of pooled multi-centre structural MR data acquired at different magnetic field strengths (MFS). Aiming to minimise potential systematic bias when using ADNI data we investigate the specific contributions of spatial registration strategies and the impact of MFS on voxel-based morphometry in AD. We perform a whole-brain analysis within the framework of Statistical Parametric Mapping, testing for main effects of various diffeomorphic spatial registration strategies, of MFS and their interaction with disease status. Beyond the confirmation of medial temporal lobe volume loss in AD, we detect a significant impact of spatial registration strategy on estimation of AD related atrophy. Additionally, we report a significant effect of MFS on the assessment of brain anatomy (i) in the cerebellum, (ii) the precentral gyrus and (iii) the thalamus bilaterally, showing no interaction with the disease status. We provide empirical evidence in support of pooling data in multi-centre VBM studies irrespective of disease status or MFS. Copyright © 2013 Wiley Periodicals, Inc.

Measurement of HbA1c in multicentre diabetes trials - should blood samples be tested locally or sent to a central laboratory: an agreement analysis.

PubMed

Arch, Barbara N; Blair, Joanne; McKay, Andrew; Gregory, John W; Newland, Paul; Gamble, Carrol

2016-10-24

Glycated haemoglobin (HbA1c) is an important outcome measure in diabetes clinical trials. For multicentre designs, HbA1c can be measured locally at participating centres or by sending blood samples to a central laboratory. This study analyses the agreement between local and central measurements, using 1-year follow-up data collected in a multicentre randomised controlled trial (RCT) of newly diagnosed children with type I diabetes. HbA1c measurements were routinely analysed both locally and centrally at baseline and then at 3, 6, 9 and 12 months and the data reported in mmol/mol. Agreement was assessed by calculating the bias and 95 % limits of agreement, using the Bland-Altman analysis method. A predetermined benchmark for clinically acceptable margin of error between measurements was subjectively set as ±10 % for HbA1c. The percentage of pairs of measurements that were classified as clinically acceptable was calculated. Descriptive statistics were used to examine the agreement within centres. Treatment group was not considered. Five hundred and ninety pairs of measurement, representing 255 children and 15 trial centres across four follow-up time points, were compared. There was no significant bias: local measurements were an average of 0.16 mmol/mol (SD = 4.5, 95 % CI -0.2 to 0.5) higher than central. The 95 % limits of agreement were -8.6 to 9.0 mmol/mol (local minus central). Eighty percent of local measurements were within ±10 % of corresponding central measurements. Some trial centres were more varied in the differences observed between local and central measurements: IQRs ranging from 3 to 9 mmol/mol; none indicated systematic bias. Variation in agreement between HbA1c measurements was greater than had been expected although no overall bias was detected and standard deviations were similar. Discrepancies were present across all participating centres. These findings have implications for the comparison of standards of clinical care between centres, the design of future multicentre RCTs and existing quality assurance processes for HbA1c measurements. We recommend that centralised HbA1c measurement is preferable in the multicentre clinical trial setting. Eudract No. 2010-023792-25 , registered on 4 November 2010.

Attachment Styles of Dermatological Patients in Europe: A Multi-centre Study in 13 Countries.

PubMed

Szabó, Csanád; Altmayer, Anita; Lien, Lars; Poot, Françoise; Gieler, Uwe; Tomas-Aragones, Lucía; Kupfer, Jörg; Jemec, Gregor B E; Misery, Laurent; Linder, M Dennis; Sampogna, Francesca; van Middendorp, Henriët; Halvorsen, Jon Anders; Balieva, Flora; Szepietowski, Jacek C; Romanov, Dmitry; Marron, Servando E; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Dalgard, Florence

2017-07-06

Attachment styles of dermatological outpatients and satisfaction with their dermatologists were investigated within the framework of a multicentre study conducted in 13 European countries, organized by the European Society for Dermatology and Psychiatry. Attachment style was assessed with the Adult Attachment Scale. Patient satisfaction with the dermatologist was assessed with an 11-degree scale. A total of 3,635 adult outpatients and 1,359 controls participated in the study. Dermatological outpatients were less able to depend on others, were less comfortable with closeness and intimacy, and experienced similar rates of anxiety in relationships as did the controls. Participants who had secure attachment styles reported stressful life events during the last 6 months significantly less often than those who had insecure attachment styles. Patients with secure attachment styles tended to be more satisfied with their dermatologist than did insecure patients. These results suggest that secure attachment of dermatological outpatients may be a protective factor in the management of stress.

Efficacy of a standardized herbal preparation (Roidosanal®) in the treatment of hemorrhoids: A randomized, controlled, open-label multicentre study

PubMed Central

Aggrawal, Kapil; Satija, Naveen; Dasgupta, Gita; Dasgupta, Partha; Nain, Parul; Sahu, Aditya R.

2014-01-01

Background: Catechins and epicatechins are monomers of naturally occurring proanthocyanidins, which have been reported with free radical scavenging, antioxidant, antiinflammatory, antiallergic, and vasodilatory properties. Plant parts rich in proanthocyanidins have been used for years in treatment of various ano-rectal diseases. This study compares the efficacy of two herbal preparations, Daflon® 500 mg and Roidosanal®, in ameliorating the signs and symptoms associated with hemorrhoids. Objective: To evaluate the safety and to compare the efficacy of a herbal preparation, Roidosanal® versus Daflon® 500 mg, on signs and symptoms of hemorrhoidal disease. Materials and Methods: In this pilot, active controlled, open-labeled multicentre study, 73 patients with proctoscopy proven hemorrhoids (Grade I to III) were randomly assigned to receive either Roidosanal® (Gr R; n = 37) or Daflon® 500 mg (Gr D; n = 36), for 15 days, at three centers in India. Assessment of hemorrhoidal symptoms was carried out in all patients at different time points. Intent-to-treat analysis was performed for both primary and secondary endpoints. Results: Baseline characteristics were comparable between the two groups. Both products were found to be equally effective in improving the ano-rectal conditions in Grade I and Grade II hemorrhoids; however, Roidosanal® demonstrated better efficacy in patients with Grade III hemorrhoids. Hemorrhoids associated symptoms like bleeding, pain, etc., improved in both groups, although intergroup comparisons were comparable. Conclusion: Both Roidosanal® and Daflon® 500 mg were equally effective in resolving signs and symptoms of hemorrhoids. Roidosanal® can be tried as a safe and effective treatment option for treatment of hemorrhoids. Further randomized, double-blind and large multicentre studies are recommended. PMID:24948863

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.

PubMed

Seufert, R; Sedlacek, L; Kahl, B; Hogardt, M; Hamprecht, A; Haase, G; Gunzer, F; Haas, A; Grauling-Halama, S; MacKenzie, C R; Essig, A; Stehling, F; Sutharsan, S; Dittmer, S; Killengray, D; Schmidt, D; Eskandarian, N; Steinmann, E; Buer, J; Hagen, F; Meis, J F; Rath, P-M; Steinmann, J

2018-04-19

Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

PubMed

Hoare, Brian; Ditchfield, Michael; Thorley, Megan; Wallen, Margaret; Bracken, Jenny; Harvey, Adrienne; Elliott, Catherine; Novak, Iona; Crichton, Ali

2018-05-08

Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

A Randomised Multi-centre Study to Compare the Long-term Performance of the Future Hip to 3 Other Implants in Primary Total Hip Replacement

ClinicalTrials.gov

2016-10-06

Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis; Perthes Disease

A Multi-centre Study to Assess the Long-term Performance of the Pinnacle™ Cup With a Polyethylene-on-metal Bearing in Primary Total Hip Replacement

ClinicalTrials.gov

2017-06-27

Rheumatoid Arthritis; Osteoarthritis; Post-traumatic Arthritis; Collagen Disorders; Avascular Necrosis; Traumatic Femoral Fractures; Nonunion of Femoral Fractures; Congenital Hip Dysplasia; Slipped Capital Femoral Epiphysis

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence.

PubMed

Müller, Ueli C; Asherson, Philip; Banaschewski, Tobias; Buitelaar, Jan K; Ebstein, Richard P; Eisenberg, Jaques; Gill, Michael; Manor, Iris; Miranda, Ana; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Sergeant, Joseph A; Sonuga-Barke, Edmund Js; Thompson, Margaret; Faraone, Stephen V; Steinhausen, Hans-Christoph

2011-04-07

The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures. Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures. Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores. When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

Sulfur Contamination in the Florida Everglades: Initial Examination of Mitigation Strategies

USGS Publications Warehouse

Orem, William H.

2007-01-01

INTRODUCTION Sulfate contamination of the Everglades is a serious water quality issue facing restoration of this ecosystem. Sulfate concentrations in some marsh areas are more than 60 times background concentrations, and sulfate in excess of background levels covers an estimated 60% of the freshwater Everglades (Orem et al., 1997; Stober et al., 1996 and 2001; Orem et al., 2004). The excess sulfate enters the Everglades in the discharge of canal water from the Everglades Agricultural Area (EAA). Excess phosphorus also enters the ecosystem in EAA canal water discharge (Koch and Reddy, 1992; Craft and Richardson, 1993; DeBusk et al. 1994; Zielinski et al., 1999). Existing data suggest that sulfur in fertilizer and soil amendments used in the EAA (both new additions and legacy sulfur in the soil) is a major source of excess sulfate entering the ecosystem (Bates et al., 2001 and 2002). Other potential sources of sulfate (including groundwater), however, need further investigation. The report by Gilmour et al. (2007b) in the 2007 South Florida Environmental Report provides a complete examination of the current state of knowledge of the sulfur contamination issue in the Everglades. Sulfate discharged from canals or leaking through levees into the ecosystem spreads out over a large area since, unlike phosphorus, it is not removed to any great extent by plant uptake. Sulfate slowly diffuses into the anoxic soils (peats) underlying the Everglades and stimulates microbial sulfate reduction (MSR), producing toxic hydrogen sulfide as a byproduct (Goldhaber and Kaplan, 1974; Berner, 1980; Rheinheimer, 1994). Hydrogen sulfide at contaminated sites may build up in sediments to concentrations thousands of times background levels (Gilmour et al., 2007b). The excess sulfate and sulfide has numerous deleterious impacts on the Everglades. One of the more environmentally important impacts is the link between sulfate contamination and methylmercury (MeHg) production in the ecosystem (Gilmour et al., 1998; Benoit et al., 1998, 1999a, b; Axelrad et al., 2007; Gilmour et al., 2007a). MeHg, a bioaccumulative neurotoxin, is produced primarily by methylation of ambient inorganic mercury during MSR (Compeau and Bartha, 1985; Gilmour et al., 1992; Munthe et al., 1995; Branfireun et al., 1999). Contamination of fish with MeHg is the most significant environmental contaminant issue in the USA in terms of number of locations impacted (Krabbenhoft and Wiener, 1999; USEPA, 1998). Neurotoxic MeHg represents a serious threat to wildlife (Bouton et al., 1999; Frederick et al., 1999; Heath and Frederick, 2005), and is a human health issue, with human exposure through fish consumption (Gilbert and Grant-Webster, 1995; Schober et al., 2003). In addition to its neurotoxic effects, MeHg may also be an endocrine disruptor that affects successful reproduction in fish and fish-eating wildlife (Klaper et al., 2006). South Florida has among the highest levels of MeHg in fish in the USA (Lambou et al., 1991). Experimental chamber (mesocosm) studies conducted in the Everglades have shown that sulfate addition stimulates the production and bioaccumulation of MeHg (Gilmour et al., 2007b). Inorganic mercury enters the Everglades primarily in rainfall, and most of the inorganic mercury in the rainfall appears to originate from outside of the USA (Hanisch, 1998). The origin of most inorganic mercury from outside of the USA severely limits the ability of state and Federal officials to limit MeHg production and bioaccumulation in fish in the Everglades by controlling emissions of inorganic mercury from various anthropogenic sources (e.g. coal-fired power plants, medical waste incinerators, cement manufacture). Thus, controlling sulfate inputs to the Everglades may represent the most effective way of minimizing MeHg production and bioaccumulation here. In addition to impacts on MeHg production and bioaccumulation, sulfur contamination has also dramatically altered redox p

Multicentric primary extramammary Paget disease: a Toker cell disorder?

PubMed

Hashemi, Pantea; Kao, Grace F; Konia, Thomas; Kauffman, Lisa C; Tam, Christine C; Sina, Bahram

2014-07-01

Toker cells are epithelial clear cells found in the areolar and nipple areas of the breast, vulvar region, and other apocrine gland-bearing areas of the skin. Toker cells have been implicated in the pathogenesis of clear cell papulosis, cutaneous hamartoma with pagetoid cells, and rare cases of primary extramammary Paget disease (EMPD) but not in secondary EMPD with underlying adenocarcinoma. The pathogenesis of primary EMPD is not well defined. We report a case of multicentric primary EMPD with evidence of Toker cell proliferation and nonaggressive biologic behavior in a 63-year-old white man. A detailed description of the morphologic and biologic features of Toker cells and their possible carcinogenetic links also are discussed. Based on the observation and follow-up of our patient, we hypothesize that multicentric primary EMPD starts with Toker cell hyperplasia and can potentially evolve to carcinoma in the genital region.

[Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

PubMed

Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

2013-01-01

Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

The challenges of implementing a multi-centre audit of end-of-life care in care homes.

PubMed

Levy, Jean; Kinley, Julie; Conway, Frances

2016-11-02

This article aims to share the experience of a hospice in facilitating a multi-centre audit of end-of-life care in care homes, particularly noting the challenges and enablers of carrying out the audit. The audit was a retrospective multi-centre survey of bereaved relatives/next of kin of residents who died in the care home, using an anonymous, validated questionnaire: the Family Perception of Care Scale. Questionnaires were sent 3-months after bereavement. Returned questionnaires were analysed using SPSS and Excel. The care homes were in areas encompassing outer and inner city populations. The team identified eight challenges to the audit process, in particular, embedding procedures within the care homes, non-responses and developing action plans for improvement. Overall, the audit provided an indication of where improvements could be made and where care was already excellent, built confidence and increased expertise in the care-home staff.

Emergence agitation during recovery from intracranial surgery under general anaesthesia: a protocol and statistical analysis plan for a prospective multicentre cohort study.

PubMed

Yan, Li-Mei; Chen, Han; Yu, Rong-Guo; Wang, Zhu-Heng; Zhou, Guan-Hua; Wang, Yong-Jin; Zhang, Xia; Xu, Ming; Chen, Lu; Zhou, Jian-Xin

2015-04-21

Emergence agitation after intracranial surgery is an important clinical issue during anaesthesia recovery. The aim of this multicentre cohort study is to investigate the incidence of emergence agitation, identify the risk factors and determine clinical outcomes in adult patients after intracranial surgery under general anaesthesia. Additionally, we will deliberately clarify the relationship between postoperative pneumocephalus and agitation. The present study is a prospective multicentre cohort study. Five intensive care units (ICUs) in China will participate in the study. Consecutive adult patients admitted to the ICUs after intracranial surgery will be enrolled. Sedation-Agitation Scale (SAS) or Richmond Agitation-Sedation Scale (RASS) will be used to evaluate the patients 12 h after the enrolment. Agitation is defined as an SAS score of 5-7, or an RASS score of +2 to +4. According to the maximal SAS and RASS score, patients will be divided into two cohorts: the agitation group and the non-agitation group. Factors potentially related to emergence agitation will be collected at study entry, during anaesthesia and operation, during postoperative care. Univariate analyses between the agitation and the non-agitation groups will be performed. The stepwise backward logistic regression will be carried out to identify the independent predictors of agitation. Patients will be followed up for 72 h after the operation. Accidental self-extubation of the endotracheal tube and removal of other catheters will be documented. The use of sedatives and analgesics will be collected. Ethics approval has been obtained from each of five participating hospitals. Study findings will be disseminated through peer-reviewed publications and conference presentations. NCT02318199. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of combined exercise training and electromyostimulation treatments in chronic heart failure: A prospective multicentre study.

PubMed

Iliou, Marie C; Vergès-Patois, Bénédicte; Pavy, Bruno; Charles-Nelson, Anais; Monpère, Catherine; Richard, Rudy; Verdier, Jean C

2017-08-01

Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure. It is a valuable method for the improvement of exercise tolerance. Some studies reported a similar improvement with quadricipital electrical myostimulation, but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospective multicentre study. Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and/or muscular strength in cardiac heart failure patients. Methods Ninety-one patients were included (mean age: 58 ± 9 years; New York Heart Association II/III: 52/48%, left ventricular ejection fraction: 30 ± 7%) in a prospective French study. The patients were randomised into two groups: 41 patients in exercise training and 50 in exercise training + electrical myostimulation. All patients underwent 20 exercise training sessions. In addition, in the exercise training + electrical myostimulation group, patients underwent 20 low frequency (10 Hz) quadricipital electrical myostimulation sessions. Each patient underwent a cardiopulmonary exercise test, a six-minute walk test, a muscular function evaluation and a quality of life questionnaire, before and at the end of the study. Results A significant improvement of exercise capacity (Δ peak oxygen uptake+15% in exercise training group and +14% in exercise training + electrical myostimulation group) and of quality of life was observed in both groups without statistically significant differences between the two groups. Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group. Conclusions This prospective multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients.

The group-based social skills training SOSTA-FRA in children and adolescents with high functioning autism spectrum disorder - study protocol of the randomised, multi-centre controlled SOSTA - net trial

PubMed Central

2013-01-01

Background Group-based social skills training (SST) has repeatedly been recommended as treatment of choice in high-functioning autism spectrum disorder (HFASD). To date, no sufficiently powered randomised controlled trial has been performed to establish efficacy and safety of SST in children and adolescents with HFASD. In this randomised, multi-centre, controlled trial with 220 children and adolescents with HFASD it is hypothesized, that add-on group-based SST using the 12 weeks manualised SOSTA–FRA program will result in improved social responsiveness (measured by the parent rated social responsiveness scale, SRS) compared to treatment as usual (TAU). It is further expected, that parent and self reported anxiety and depressive symptoms will decline and pro-social behaviour will increase in the treatment group. A neurophysiological study in the Frankfurt HFASD subgroup will be performed pre- and post treatment to assess changes in neural function induced by SST versus TAU. Methods/design The SOSTA – net trial is designed as a prospective, randomised, multi-centre, controlled trial with two parallel groups. The primary outcome is change in SRS score directly after the intervention and at 3 months follow-up. Several secondary outcome measures are also obtained. The target sample consists of 220 individuals with ASD, included at the six study centres. Discussion This study is currently one of the largest trials on SST in children and adolescents with HFASD worldwide. Compared to recent randomised controlled studies, our study shows several advantages with regard to in- and exclusion criteria, study methods, and the therapeutic approach chosen, which can be easily implemented in non-university-based clinical settings. Trial registration ISRCTN94863788 – SOSTA – net: Group-based social skills training in children and adolescents with high functioning autism spectrum disorder. PMID:23289935

Influence of quality of care and individual patient characteristics on quality of life and return to work in survivors of the acute respiratory distress syndrome: protocol for a prospective, observational, multi-centre patient cohort study (DACAPO).

PubMed

Brandstetter, Susanne; Dodoo-Schittko, Frank; Blecha, Sebastian; Sebök, Philipp; Thomann-Hackner, Kathrin; Quintel, Michael; Weber-Carstens, Steffen; Bein, Thomas; Apfelbacher, Christian

2015-12-17

Health-related quality of life (HRQoL) and return to work are important outcomes in critical care medicine, reaching beyond mortality. Little is known on factors predictive of HRQoL and return to work in critical illness, including the acute respiratory distress syndrome (ARDS), and no evidence exists on the role of quality of care (QoC) for outcomes in survivors of ARDS. It is the aim of the DACAPO study ("Surviving ARDS: the influence of QoC and individual patient characteristics on quality of life") to investigate the role of QoC and individual patient characteristics on quality of life and return to work. A prospective, observational, multi-centre patient cohort study will be performed in Germany, using hospitals from the "ARDS Network Germany" as the main recruiting centres. It is envisaged to recruit 2400 patients into the DACAPO study and to analyse a study population of 1500 survivors. They will be followed up until 12 months after discharge from hospital. QoC will be assessed as process quality, structural quality and volume at the institutional level. The main outcomes (HRQoL and return to work) will be assessed by self-report questionnaires. Further data collection includes general medical and ARDS-related characteristics of patients as well as sociodemographic and psycho-social parameters. Multilevel hierarchical modelling will be performed to analyse the effects of QoC and individual patient characteristics on outcomes, taking the cluster structure of the data into account. By obtaining comprehensive data at patient and hospital level using a prospective multi-centre design, the DACAPO-study is the first study investigating the influence of QoC on individual outcomes of ARDS survivors.

Assessment of temporal association of relapse of canine multicentric lymphoma with components of the CHOP protocol: Is cyclophosphamide the weakest link?

PubMed

Wang, Shang-Lin; Lee, Jih-Jong; Liao, Albert Taiching

2016-07-01

Combination chemotherapy, using cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), is the most commonly used treatment for canine lymphoma. Most affected dogs respond during the initial stages of chemotherapy, but many relapse. The aim of this study was to evaluate the relationship between the use of specific chemotherapy drugs and clinical relapse, using the modified Madison-Wisconsin, 25 week chemotherapy protocol. Forty-one of 68 dogs affected with multicentric lymphoma relapsed during the treatment period. Relapse occurred more frequently after the administration of cyclophosphamide (n = 24; P < 0.01), compared with vincristine (n = 9) or doxorubicin (n = 5). Therefore, the therapeutic outcome of traditional CHOP-based chemotherapy might be improved by replacing cyclophosphamide with other cytotoxic drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cognitive Modifiability of Children with Developmental Disabilities: A Multicentre Study Using Feuerstein's Instrumental Enrichment-Basic Program

ERIC Educational Resources Information Center

Kozulin, A.; Lebeer, J.; Madella-Noja, A.; Gonzalez, F.; Jeffrey, I.; Rosenthal, N.; Koslowsky, M.

2010-01-01

The study aimed at exploring the effectiveness of cognitive intervention with the new "Instrumental Enrichment Basic" program (IE-basic), based on Feuerstein's theory of structural cognitive modifiability that contends that a child's cognitive functioning can be significantly modified through mediated learning intervention. The IE-basic…

[Multicenter randomized trial of amnioinfusion].

PubMed

Fraser, W; Marcoux, S; Prendiville, W; Petrou, S; Hofmeyr, J; Reinharz, D; Goulet, C; Ohlsson, A

2000-05-01

Meconium staining of the amniotic fluid in labor is a frequent problem that is associated with an increase in the risk of neonatal and maternal morbidity. Amnioinfusion is a simple technique that is designed to prevent neonatal and maternal morbidity associated with meconium. Preliminary studies indicate that amnioinfusion is a promising approach to the prevention of such complications of labor. However, further research is required. The primary objective of this multi-centre randomized controlled study is to determine if amnioinfusion for thick meconium stained amniotic fluid results in a reduction in perinatal death or moderate to severe meconium aspiration syndrome. We will also assess the effects of amnioinfusion on other indicators of neonatal morbidity and on cesarean section. The study includes an evaluation of womens views on their childbirth experience and an economic evaluation of a policy of amnioinfusion The study will be achieved with the collaboration of approximately 50 obstetrical centres from across Canada, US, Europe, South America and South Africa. This multicentre trial will provide urgently needed information on the efficacy and effectiveness of amniofusion for the indication of meconium stained amniotic fluid.

Colorectal cancer and its association with the metabolic syndrome: a Malaysian multi-centric case-control study.

PubMed

Ulaganathan, V; Kandiah, M; Zalilah, M S; Faizal, J A; Fijeraid, H; Normayah, K; Gooi, B H; Othman, R

2012-01-01

Colorectal cancer (CRC) and the metabolic syndrome (MetS) are both on the rise in Malaysia. A multi-centric case-control study was conducted from December 2009 to January 2011 to determine any relationship between the two. Patients with confirmed CRC based on colonoscopy findings and cancer free controls from five local hospitals were assessed for MetS according to the International Diabetes Federation (IDF) definition. Each index case was matched for age, gender and ethnicity with two controls (140: 280). MetS among cases was highly prevalent (70.7%), especially among women (68.7%). MetS as an entity increased CRC risk by almost three fold independently (OR=2.61, 95%CI=1.53-4.47). In men MetS increased the risk of CRC by two fold (OR=2.01, 95%CI, 1.43-4.56), demonstrating an increasing trend in risk with the number of Mets components observed. This study provides evidence for a positive association between the metabolic syndrome and colorectal cancer. A prospective study on the Malaysian population is a high priority to confirm these findings.

Development and validation of a paediatric long-bone fracture classification. A prospective multicentre study in 13 European paediatric trauma centres

PubMed Central

2011-01-01

Background The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Methods Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. Results The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of κ = 0.71 with no significant difference between experienced and less experienced raters. Conclusions In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future. PMID:21548939

Endoscopic tri-modal imaging for detection of early neoplasia in Barrett's oesophagus: a multi-centre feasibility study using high-resolution endoscopy, autofluorescence imaging and narrow band imaging incorporated in one endoscopy system.

PubMed

Curvers, W L; Singh, R; Song, L-M Wong-Kee; Wolfsen, H C; Ragunath, K; Wang, K; Wallace, M B; Fockens, P; Bergman, J J G H M

2008-02-01

To investigate the diagnostic potential of endoscopic tri-modal imaging and the relative contribution of each imaging modality (i.e. high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI)) for the detection of early neoplasia in Barrett's oesophagus. Prospective multi-centre study. Tertiary referral centres. 84 Patients with Barrett's oesophagus. The Barrett's oesophagus was inspected with HRE followed by AFI. All lesions detected with HRE and/or AFI were subsequently inspected in detail by NBI for the presence of abnormal mucosal and/or microvascular patterns. Biopsies were obtained from all suspicious lesions for blinded histopathological assessment followed by random biopsies. (1) Number of patients with early neoplasia diagnosed by HRE and AFI; (2) number of lesions with early neoplasia detected with HRE and AFI; and (3) reduction of false positive AFI findings after NBI. Per patient analysis: AFI identified all 16 patients with early neoplasia identified with HRE and detected an additional 11 patients with early neoplasia that were not identified with HRE. In three patients no abnormalities were seen but random biopsies revealed HGIN. After HRE inspection, AFI detected an additional 102 lesions; 19 contained HGIN/EC (false positive rate of AFI after HRE: 81%). Detailed inspection with NBI reduced this false positive rate to 26%. In this international multi-centre study, the addition of AFI to HRE increased the detection of both the number of patients and the number of lesions with early neoplasia in patients with Barrett's oesophagus. The false positive rate of AFI was reduced after detailed inspection with NBI.

One-year multicentre outcomes of transapical aortic valve implantation using the SAPIEN XT™ valve: the PREVAIL transapical study.

PubMed

Walther, Thomas; Thielmann, Matthias; Kempfert, Joerg; Schroefel, Holger; Wimmer-Greinecker, Gerhard; Treede, Hendrik; Wahlers, Thorsten; Wendler, Olaf

2013-05-01

The study aimed to evaluate 1-year outcomes of the multicentre PREVAIL transapical (TA) study of TA-aortic valve implantation (AVI) in high-risk patients. From September 2009 to August 2010, a total of 150 patients, aged 81.6 ± 5.8 years, 40.7% female, were included at 12 European TA-AVI experienced sites. Patients received 23 (n = 36), 26 (n = 57) and 29 mm (n = 57) second-generation SAPIEN XT™ (Edwards Lifesciences, Irvine, CA, USA) valves. The mean logistic EuroSCORE was 24.3 ± 7.0, and mean Society Thoracic Surgeons score was 7.5 ± 4.4%. Survival was 91.3% at 30 days and 77.9% at 1 year. Subgroup analysis revealed survivals of 91.7/88.9, 86.0/70.2, 96.55/91.2% for patients receiving 23-, 26- and 29-mm valves at 30 days and at 1 year, respectively. Transthoracic echocardiography revealed preserved left ventricular ejection fraction and low gradients. Aortic incompetence was none in 41/48, trace 30/36, mild 22/12 and moderate in 7/4% at discharge and 1 year. Walking distance increased from 221 (postimplant) to 284 m (at 1 year, P = 0.0004). Three patients required reoperation due to increasing aortic incompetence during follow-up. Causes of mortality at 1 year were cardiac (n = 7), stroke (n = 1) and others (n = 5). The European PREVAIL multicentre trial demonstrates good functionality and good outcomes for TA-AVI using the second-generation SAPIEN XT prosthesis and the ASCENDRA-II delivery system. The 29-mm SAPIEN XT valve was successfully introduced and showed excellent results.

Involving older people in a multi-centre randomised trial of a complex intervention in pre-hospital emergency care: implementation of a collaborative model.

PubMed

Koniotou, Marina; Evans, Bridie Angela; Chatters, Robin; Fothergill, Rachael; Garnsworthy, Christopher; Gaze, Sarah; Halter, Mary; Mason, Suzanne; Peconi, Julie; Porter, Alison; Siriwardena, A Niroshan; Toghill, Alun; Snooks, Helen

2015-07-10

Health services research is expected to involve service users as active partners in the research process, but few examples report how this has been achieved in practice in trials. We implemented a model to involve service users in a multi-centre randomised controlled trial in pre-hospital emergency care. We used the generic Standard Operating Procedure (SOP) from our Clinical Trials Unit (CTU) as the basis for creating a model to fit the context and population of the SAFER 2 trial. In our model, we planned to involve service users at all stages in the trial through decision-making forums at 3 levels: 1) strategic; 2) site (e.g. Wales; London; East Midlands); 3) local. We linked with charities and community groups to recruit people with experience of our study population. We collected notes of meetings alongside other documentary evidence such as attendance records and study documentation to track how we implemented our model. We involved service users at strategic, site and local level. We also added additional strategic level forums (Task and Finish Groups and Writing Days) where we included service users. Service user involvement varied in frequency and type across meetings, research stages and locations but stabilised and increased as the trial progressed. Involving service users in the SAFER 2 trial showed how it is feasible and achievable for patients, carers and potential patients sharing the demographic characteristics of our study population to collaborate in a multi-centre trial at the level which suited their health, location, skills and expertise. A standard model of involvement can be tailored by adopting a flexible approach to take account of the context and complexities of a multi-site trial. Current Controlled Trials ISRCTN60481756. Registered: 13 March 2009.

Dose escalation study to evaluate safety, tolerability and efficacy of intravenous etoposide phosphate administration in 27 dogs with multicentric lymphoma

PubMed Central

Hordeaux, Juliette; Bouchaert, Emmanuel; Gomes, Bruno

2017-01-01

Comparative oncology has shown that naturally occurring canine cancers are of valuable and translatable interest for the understanding of human cancer biology and the characterization of new therapies. This work was part of a comparative oncology project assessing a new, clinical-stage topoisomerase II inhibitor and comparing it with etoposide in dogs with spontaneous lymphoma with the objective to translate findings from dogs to humans. Etoposide is a topoisomerase II inhibitor widely used in various humans’ solid and hematopoietic cancer, but little data is available concerning its potential antitumor efficacy in dogs. Etoposide phosphate is a water-soluble prodrug of etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous etoposide phosphate in dogs with multicentric lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric lymphoma were enrolled and treated with three cycles of etoposide phosphate IV injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no hypersensitivity reaction were reported at this dose level. Beyond the characterization of etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human lymphomas. PMID:28505195

Glutamatergic modulation of separation distress: profound emotional effects of excitatory amino acids in chicks.

PubMed

Normansell, Larry; Panksepp, Jaak

2011-10-01

Pre-clinical models of brain affective circuits provide relevant evidence for understanding the brain systems that figure heavily in psychiatric disorders. Social isolation and the resulting separation distress contribute to the onset of depression. In this work, the effects of excitatory amino acids (EAA) on isolation-induced distress vocalization (DV) were assessed in young domestic chicks. Both glutamate and quisqualate (QA) produced dose-dependent reductions in DVs, while N-methyl-d-aspartate (NMDA) and kainate (KA) increased DVs. Such a differential pattern of responsiveness may indicate the presence of reciprocal or interacting EAA systems in the brain control of separation distress. Administration of either the NMDA receptor antagonist 2-amino-5-phosphonovalerate (APV) or the broad-spectrum antagonist gamma-d-glutamylglycine (DGG) greatly reduced DVs, as did the antagonist 2-amino-4-phosphonobutyrate (APB). APV did not attenuate the increase in vocalizations seen after NMDA or KA administration. DGG, however, was able to block the increase in calling produced by either of these agonists, suggesting a KA receptor mechanism. KA treatment inhibited the ability of other chicks, or auditory and somatosensory information, to suppress DVs. KA-treated animals exhibited a hyperemotional behavior pattern during which a variety of motivated behaviors were disrupted including reactions to novel objects, approaching the flock, and foraging. They could not sustain a coherent flock-like social cohesion, but exhibited strong fixed-action patterns of flight interspersed with hiding and crouching behaviors. The evident behavioral changes suggest that glutamatergic synapses directly influence sensory, motor and emotional processes in the brain and may be especially important in the integration of environmental stimuli with emotional central state processes of animals. Considering that unresolved social loss and grief have been deemed to be among the main precipitating causes of depression, and glutamate plays a large role in the production of negative effect related to separation distress, these results are consistent with the emerging work targeting glutamate blockade as a way to produce rapid anti-depressant effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multicenter external validation of two malignancy risk prediction models in patients undergoing 18F-FDG-PET for solitary pulmonary nodule evaluation.

PubMed

Perandini, Simone; Soardi, G A; Larici, A R; Del Ciello, A; Rizzardi, G; Solazzo, A; Mancino, L; Zeraj, F; Bernhart, M; Signorini, M; Motton, M; Montemezzi, S

2017-05-01

To achieve multicentre external validation of the Herder and Bayesian Inference Malignancy Calculator (BIMC) models. Two hundred and fifty-nine solitary pulmonary nodules (SPNs) collected from four major hospitals which underwent 18-FDG-PET characterization were included in this multicentre retrospective study. The Herder model was tested on all available lesions (group A). A subgroup of 180 SPNs (group B) was used to provide unbiased comparison between the Herder and BIMC models. Receiver operating characteristic (ROC) area under the curve (AUC) analysis was performed to assess diagnostic accuracy. Decision analysis was performed by adopting the risk threshold stated in British Thoracic Society (BTS) guidelines. Unbiased comparison performed In Group B showed a ROC AUC for the Herder model of 0.807 (95 % CI 0.742-0.862) and for the BIMC model of 0.822 (95 % CI 0.758-0.875). Both the Herder and the BIMC models were proven to accurately predict the risk of malignancy when tested on a large multicentre external case series. The BIMC model seems advantageous on the basis of a more favourable decision analysis. • The Herder model showed a ROC AUC of 0.807 on 180 SPNs. • The BIMC model showed a ROC AUC of 0.822 on 180 SPNs. • Decision analysis is more favourable to the BIMC model.

A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

PubMed Central

2010-01-01

Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

Multicentric GISCoR Study "intensive clinical follow-up versus surgical radicalization after complete endoscopic polypectomy of a malignant adenoma" (SEC-GISCoR).

PubMed

Andreoni, Bruno; Camellini, Lorenzo; Sonzogni, Angelica; Crosta, Cristiano; Pirola, Maria Elena; Corbellini, Carlo

2011-09-01

Colorectal cancer screening programs result in an early diagnosis of the disease. In 2007, 250 malignant polyps were identified in Lombardy, out of 1,329 screen-detected colorectal carcinomas. The Italian Group for Colorectal Cancer (GISCoR) promoted the multicentric study "Endoscopic Follow-up versus Surgical Radicalization of Malignant Polyps after Complete Endoscopic Polypectomy" (SEC-GISCoR). The protocol was a multicentric, prospective, observational, non-randomized study. It included patients diagnosed a colorectal malignant adenoma, after complete endoscopic removal. From November 2005 to September 2009, three participating centers enrolled 120 patients with malignant polyps after "complete" endoscopic polypectomy; malignant polyps were classified as "low risk" or "high risk". The study had two arms: "Intensive follow-up" (42 patients: 32 with low-risk and 10 with high-risk polyps) and "Surgical radicalization" (78 patients: 5 with low-risk and 73 with high-risk polyps). Data were collected using an online CRF. Overall, 37/120 polyps (30.8%) were low risk and 83/120 (69.2%) were high risk. 42 out of 120 patients (35%) were enrolled in the "clinical follow-up" arm, while 78/120 (65%) entered the surgery arm. In 15 cases, patients were not enrolled in the correct arm, according to the criteria agreed upon before starting the study. There still is a high incidence (11.5%) of pathological mismatches. No clinical event was reported in 2.9 years of follow-up. In conclusion, some differences emerged in the management of patients with malignant polyps among participating centers (p < 0.001), mismatches can be explained by high surgical risk or patient's choice. Only in 5 cases (4.2%), did data analysis not allow to exactly determine the reason for a choice different from protocol criteria. The availability of new risk factors and the evidence of pathological mismatches confirmed the need for future studies on this issue.

Evaluation of web-based annotation of ophthalmic images for multicentric clinical trials.

PubMed

Chalam, K V; Jain, P; Shah, V A; Shah, Gaurav Y

2006-06-01

An Internet browser-based annotation system can be used to identify and describe features in digitalized retinal images, in multicentric clinical trials, in real time. In this web-based annotation system, the user employs a mouse to draw and create annotations on a transparent layer, that encapsulates the observations and interpretations of a specific image. Multiple annotation layers may be overlaid on a single image. These layers may correspond to annotations by different users on the same image or annotations of a temporal sequence of images of a disease process, over a period of time. In addition, geometrical properties of annotated figures may be computed and measured. The annotations are stored in a central repository database on a server, which can be retrieved by multiple users in real time. This system facilitates objective evaluation of digital images and comparison of double-blind readings of digital photographs, with an identifiable audit trail. Annotation of ophthalmic images allowed clinically feasible and useful interpretation to track properties of an area of fundus pathology. This provided an objective method to monitor properties of pathologies over time, an essential component of multicentric clinical trials. The annotation system also allowed users to view stereoscopic images that are stereo pairs. This web-based annotation system is useful and valuable in monitoring patient care, in multicentric clinical trials, telemedicine, teaching and routine clinical settings.

Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma.

PubMed

Burton, J H; Garrett-Mayer, E; Thamm, D H

2013-12-01

Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization. © 2012 Blackwell Publishing Ltd.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

Ultrasonography of the medial iliac lymph nodes in the dog.

PubMed

Llabrés-Díaz, Francisco J

2004-01-01

Sixty-one medial iliac lymph nodes of 38 different dogs (eight with adenocarcinoma of the apocrine glands of the anal sac, 13 with multicentric lymphoma, six with multicentric lymphoma but in clinical remission, and 11 control dogs) were evaluated to assess the ability of ultrasound to identify and interrogate these lymph nodes across the different groups and to differentiate these groups using different sonographic parameters. Ultrasound proved to be useful to assess canine medial iliac lymph nodes. An increase in size or number of detected lymph nodes or finding rounder or heterogeneous lymph nodes could differentiate lymph nodes of dogs of the control group from lymph nodes of dogs with lymphoma or an adenocarcinoma of the apocrine glands of the anal sac. Subcategories of malignancy could not be differentiated. More studies need to be performed, both with patients with reactive lymph nodes and also focusing on other canine superficial lymph nodes, before generalizing the results of this study to other areas or diseases.

Radiofrequency-induced thermal therapy: results of a European multicentre study of resistive ablation of incompetent truncal varicose veins.

PubMed

Braithwaite, B; Hnatek, L; Zierau, U; Camci, M; Akkersdijk, Gjm; Nio, D; Sarlija, M; Ajduk, M; Santoro, P; Roche, E

2013-02-01

To investigate the effectiveness of bipolar radiofrequency-induced thermal therapy (RFITT) in a multicentre non-randomized study. Some 672 incompetent saphenous veins (85% great saphenous varicose vein, 15% short saphenous vein) in 462 patients (56.5% CEAP [clinical, aetiological, anatomical and pathological elements] class 3 or worse) were treated in eight European centres. Patients were assessed between 180 and 360 days postoperatively. Occlusion rates were determined by duplex ultrasound and compared with the power used for treatment, pull back rate and experience of the operating surgeon. Complete occlusion rates of 98.4% were achieved when treatments were performed by an experienced operator (more than 20 cases), when the maximum power setting on the RFITT generator was between 18 and 20 W and the applicator was withdrawn at a rate slower than 1.5 second/cm RFITT is efficacious, well tolerated by patients and has a low incidence of procedure-related post-operative complications.

The effectiveness of 2-implant overdentures - a pragmatic international multicentre study.

PubMed

Rashid, F; Awad, M A; Thomason, J M; Piovano, A; Spielberg, G P; Scilingo, E; Mojon, P; Müller, F; Spielberg, M; Heydecke, G; Stoker, G; Wismeijer, D; Allen, F; Feine, J S

2011-03-01

The purpose of this multicentre observational study was to determine patient satisfaction with either conventional dentures or mandibular 2-implant overdentures in a 'real world' setting. Two hundred and three edentulous patients (mean age 68·8 ± 10·4 years) were recruited at eight centres located in North America, South America and Europe. The patients were provided with new mandibular conventional dentures or implant overdentures supported by two implants and ball attachments. At baseline and at 6 months post-treatment, they rated their satisfaction with their mandibular prostheses on 100-mm visual analogue scale questionnaires. One hundred and two (50·2%) participants had valid baseline and 6-month satisfaction data. Although both groups reported improvements, the implant overdenture group reported significantly higher ratings of overall satisfaction, comfort, stability, ability to speak and ability to chew. These results suggest that edentulous patients who choose mandibular implant overdentures have significantly greater improvements in satisfaction, despite their relatively higher cost, than those who choose new conventional dentures. © 2010 Blackwell Publishing Ltd.

Antibiotic resistance and population structure of cystic fibrosis Pseudomonas aeruginosa isolates from a Spanish multi-centre study.

PubMed

López-Causapé, Carla; de Dios-Caballero, Juan; Cobo, Marta; Escribano, Amparo; Asensio, Óscar; Oliver, Antonio; Del Campo, Rosa; Cantón, Rafael; Solé, Amparó; Cortell, Isidoro; Asensio, Oscar; García, Gloria; Martínez, María Teresa; Cols, María; Salcedo, Antonio; Vázquez, Carlos; Baranda, Félix; Girón, Rosa; Quintana, Esther; Delgado, Isabel; de Miguel, María Ángeles; García, Marta; Oliva, Concepción; Prados, María Concepción; Barrio, María Isabel; Pastor, María Dolores; Olveira, Casilda; de Gracia, Javier; Álvarez, Antonio; Escribano, Amparo; Castillo, Silvia; Figuerola, Joan; Togores, Bernat; Oliver, Antonio; López, Carla; de Dios Caballero, Juan; Tato, Marta; Máiz, Luis; Suárez, Lucrecia; Cantón, Rafael

2017-09-01

The first Spanish multi-centre study on the microbiology of cystic fibrosis (CF) was conducted from 2013 to 2014. The study involved 24 CF units from 17 hospitals, and recruited 341 patients. The aim of this study was to characterise Pseudomonas aeruginosa isolates, 79 of which were recovered from 75 (22%) patients. The study determined the population structure, antibiotic susceptibility profile and genetic background of the strains. Fifty-five percent of the isolates were multi-drug-resistant, and 16% were extensively-drug-resistant. Defective mutS and mutL genes were observed in mutator isolates (15.2%). Considerable genetic diversity was observed by pulsed-field gel electrophoresis (70 patterns) and multi-locus sequence typing (72 sequence types). International epidemic clones were not detected. Fifty-one new and 14 previously described array tube (AT) genotypes were detected by AT technology. This study found a genetically unrelated and highly diverse CF P. aeruginosa population in Spain, not represented by the epidemic clones widely distributed across Europe, with multiple combinations of virulence factors and high antimicrobial resistance rates (except for colistin). Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Ultrasound in polycystic ovary syndrome--the measuring of ovarian stroma and relationship with circulating androgens: results of a multicentric study.

PubMed

Fulghesu, A M; Angioni, S; Frau, E; Belosi, C; Apa, R; Mioni, R; Xamin, N; Capobianco, G P; Dessole, S; Fruzzetti, F; Lazzarini, V; Minerba, L; Melis, G B; Lanzone, A

2007-09-01

The introduction of transvaginal approach in ultrasound (US) has enabled the accurate evaluation of the structure of the ovary and stroma. Stroma represents an acknowledged US marker for polycystic ovary syndrome (PCOS). The proportion revealed between the stroma and the ovary surface in the median section (S/A ratio) had been indicated as a reliable marker for hyperandrogenism. In order to verify the feasibility of this determination in routine use and to confirm the efficacy of S/A ratio in predicting hyperandrogenism in PCOS, a multicentric study was performed in association with five Italian research groups. A total of 418 subjects of fertile age presenting oligomenorrhoea or secondary amenorrhoea, enlarged ovaries measuring >10 cm(3) and/or >12 follicles measuring 2-9 mm in diameter took part in the study. Clinical, US and hormonal evaluations were performed in the early follicular phase or on random days in amenorrhoeic subjects. US assessment included ovarian volume, follicle number, ovarian and stroma area in median section. The hormonal study included a baseline plasma determination of LH, FSH, estradiol (E(2)), androstenedione (A), testosterone (T), dehydroepiandrosteronesulphate, 17-hydroxy-progesterone, sex hormone-binding globulin and prolactin. Correlations and receiver operator curves were used in statistical analysis of data. S/A was found to be the best significant predictor of elevated A and T levels. In order to ascertain significant cut-off values in relation to A and T levels Youden indexes were calculated and indicated 0.32 as the best cut-off for the S/A ratio. This work underlines the importance of stroma measure in improving US diagnosis of PCOS and suggest that this parameter may be used in routine clinical practice. In fact, multicentre study demonstrated the easy feasibility of such procedure without need of sophisticated machines or intensive training for operators.

PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

PubMed

de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

2010-03-18

Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

Multicentric Castleman's disease associated with inherited epidermolysis bullosa.

PubMed

Kawakami, Yoshio; Nishibu, Akiko; Kikuchi, Satoshi; Ohtsuka, Mikio; Nakamura, Koichiro; Nozawa, Yoshihiro; Abe, Masafumi; Iwatsuki, Keiji; Kaneko, Fumio

2003-09-01

Multicentric Castleman's disease (MCD) is a rare disorder characterized by fever, polyclonal hypergammaglobulinemia, and generalized lymphadenopathy. It has three histological characteristics: a recognizable architecture, germinal center abnormalities, and plasmacytosis. Inherited epidermolysis bullosa (EB) is also a rare disorder caused by a genetic defect. We report a 43-year-old patient with dystrophic EB, non-Hallopeau-Siemens recessive type or dominant type, displaying clinicopathologic features of MCD. In addition, his serum interleukin-6, which is thought to be responsible for the clinical symptoms in MCD, was elevated.

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed Central

1984-01-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide. PMID:6383234

Intra-articular radioactive yttrium and triamcinolone hexacetonide: an inconclusive trial. Arthritis and Rheumatism Council Multicentre Radiosynoviorthesis Trial Group.

PubMed

1984-08-01

A restricted sequential design multicentre controlled trial of yttrium-90 against triamcinolone intra-articularly was undertaken in patients with rheumatoid arthritis with knee involvement. The trial had to be discontinued because of dwindling recruitment over time. The reasons for this and other features contributing to an inconclusive outcome are noted. This experience lends little encouragement to the idea that yttrium-90 therapy is more or less advantageous than triamcinolone hexacetonide.

Progressive response of large intestinal bacterial community and fermentation to the stepwise decrease of dietary crude protein level in growing pigs.

PubMed

Peng, Yu; Yu, Kaifan; Mu, Chunlong; Hang, Suqin; Che, Lianqiang; Zhu, Weiyun

2017-07-01

The study aimed to determine the effects of reduction of dietary crude protein (CP) level with balanced essential amino acids (EAA) on intestinal bacteria and their metabolites of growing pigs. Forty pigs (initial BW 13.50 ± 0.50 kg, 45 ± 2 days of age) were randomly assigned to four dietary treatments containing CP levels at 20.00% (normal crude protein, NP); 17.16% (medium crude protein, MP); 15.30% (low crude protein, LP); and 13.90% (extremely low crude protein, ELP), respectively. Crystalline AAs were added to meet the EAA requirement of pigs. After 4-week feeding, eight pigs per treatment (n = 8) were randomly selected and slaughtered for sampling of ileal, cecal, and colonic digesta and mucosa. Pigs with moderately reduced CP level had increased bacterial diversity, with the Shannon diversity indices for the colon digesta in the LP group and mucosa in the MP and LP groups significantly (P < 0.05) higher than those in the NP and ELP groups. As the CP level reduces, the Bifidobacterium population were linearly decreased (P < 0.05) both in ileum, cecum, and colon, and the ELP group had the lowest Bifidobacterium population in the cecum and colon, with its value significantly lower than NP and MP groups (P < 0.05). However, the ELP group had the highest population of Escherichia coli in the colon, with its value significantly higher than the LP group (P < 0.05). For bacterial metabolites, as CP level decreased, total short-chain fatty acid (T-SCFA), acetate, and butyrate were linearly increased (linear, P < 0.05) in the ileum, while all SCFAs except formate in the cecum and T-SCFA and acetate in the colon, were linearly decreased (P < 0.05). Reducing CP level led to a linear decrease of microbial crude protein (MCP) in the ileum (P < 0.05) and ammonia in all intestine segments (P < 0.05). The spermidine in cecum and total amines, cadaverine, methylamine, and spermidine in colon were shown a quadratic change (P < 0.05) as dietary CP decreases, with the highest concentration in LP group. These findings suggest that moderate reduction of dietary CP level may benefit large intestinal bacterial community and its fermentation, which was negatively affected by extremely low CP diet.

Internet-based transfer of cardiac ultrasound images

NASA Technical Reports Server (NTRS)

Firstenberg, M. S.; Greenberg, N. L.; Garcia, M. J.; Morehead, A. J.; Cardon, L. A.; Klein, A. L.; Thomas, J. D.

2000-01-01

A drawback to large-scale multicentre studies is the time required for the centralized evaluation of diagnostic images. We evaluated the feasibility of digital transfer of echocardiographic images to a central laboratory for rapid and accurate interpretation. Ten patients undergoing trans-oesophageal echocardiographic scanning at three sites had representative single images and multiframe loops stored digitally. The images were analysed in the ordinary way. All images were then transferred via the Internet to a central laboratory and reanalysed by a different observer. The file sizes were 1.5-72 MByte and the transfer rates achieved were 0.6-4.8 Mbit/min. Quantitative measurements were similar between most on-site and central laboratory measurements (all P > 0.25), although measurements differed for left atrial width and pulmonary venous systolic velocities (both P < 0.05). Digital transfer of echocardiographic images and data to a central laboratory may be useful for multicentre trials.

DALI: Defining Antibiotic Levels in Intensive care unit patients: a multi-centre point of prevalence study to determine whether contemporary antibiotic dosing for critically ill patients is therapeutic.

PubMed

Roberts, Jason A; De Waele, Jan J; Dimopoulos, George; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Lipman, Jeffrey

2012-07-06

The clinical effects of varying pharmacokinetic exposures of antibiotics (antibacterials and antifungals) on outcome in infected critically ill patients are poorly described. A large-scale multi-centre study (DALI Study) is currently underway describing the clinical outcomes of patients achieving pre-defined antibiotic exposures. This report describes the protocol. DALI will recruit over 500 patients administered a wide range of either beta-lactam or glycopeptide antibiotics or triazole or echinocandin antifungals in a pharmacokinetic point-prevalence study. It is anticipated that over 60 European intensive care units (ICUs) will participate. The primary aim will be to determine whether contemporary antibiotic dosing for critically ill patients achieves plasma concentrations associated with maximal activity. Secondary aims will compare antibiotic pharmacokinetic exposures with patient outcome and will describe the population pharmacokinetics of the antibiotics included. Various subgroup analyses will be conducted to determine patient groups that may be at risk of very low or very high concentrations of antibiotics. The DALI study should inform clinicians of the potential clinical advantages of achieving certain antibiotic pharmacokinetic exposures in infected critically ill patients.

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

PubMed

Curran, K; Thamm, D H

2016-08-01

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments. © 2015 John Wiley & Sons Ltd.

Should Aggressive Surgical Local Control Be Attempted in All Patients with Metastatic or Pelvic Ewing's Sarcoma?

PubMed Central

Thorpe, Steven W.; Weiss, Kurt R.; Goodman, Mark A.; Heyl, Alma E.; McGough, Richard L.

2012-01-01

In previous reports, patients with Ewing's sarcoma received radiation therapy (XRT) for definitive local control because metastatic disease and pelvic location were thought to preclude aggressive local treatment. We sought to determine if single-site metastatic disease should be treated differently from multicentric-metastatic disease. We also wanted to reinvestigate the impact of XRT, pelvic location, and local recurrence on outcomes. Our results demonstrated a significant difference in overall survival (OS) between patients with either localized disease or a single-metastatic site and patients with multicentric-metastatic disease (P = 0.004). Local control was also found to be an independent predictor of outcomes as demonstrated by a significant difference in OS between those with and without local recurrence (P = 0.001). Axial and pelvic location did not predict a decreased OS. Based on these results, we concluded that pelvic location and the diagnosis of metastatic disease at diagnosis should not preclude aggressive local control, except in cases of multicentric-metastatic disease. PMID:22550427

MULTICENTRIC T-CELL LYMPHOMA AND CUTANEOUS HEMANGIOSARCOMA IN A CAPTIVE CHEETAH (ACINONYX JUBATUS).

PubMed

Lindemann, Dana M; Carpenter, James W; Nietfeld, Jerome C; Gonzalez, Estehela; Hallman, Mackenzie; Hause, Ben M

2015-12-01

A 13-yr-old intact male cheetah (Acinonyx jubatus) presented for evaluation after a 4-mo history of intermittent lethargy and increased expiratory effort. The clinical signs were initially noted after the diagnosis and death of its 13-yr-old male sibling with solitary hepatic T-cell lymphoma. Physical examination findings included thin body condition, harsh lung sounds, peripheral lymphadenopathy, and a cutaneous mass on the right medial tarsus and scrotum. Excisional biopsies diagnosed well-differentiated cutaneous hemangiosarcomas. Thoracic radiographs revealed a cranial mediastinal mass. Complete blood count and serum biochemical analyses showed a leukocytosis with persistent lymphocytosis, progressive azotemia, and markedly elevated alkaline phosphatase. Because of the cheetah's declining quality of life, euthanasia was elected. Postmortem examination, histopathology, and immunohistochemical staining revealed multicentric T-cell lymphoma. Feline leukemia virus (FeLV) enzyme-linked immunosorbent assay, FeLV polymerase chain reaction (whole blood), and viral metagenomic analysis were negative. This is the first case of cutaneous hemangiosarcoma and multicentric T-cell lymphoma reported in a FeLV-negative cheetah.

Understanding Resident Ratings of Teaching in the Workplace: A Multi-Centre Study

ERIC Educational Resources Information Center

Fluit, Cornelia R. M. G.; Feskens, Remco; Bolhuis, Sanneke; Grol, Richard; Wensing, Michel; Laan, Roland

2015-01-01

Providing clinical teachers with feedback about their teaching skills is a powerful tool to improve teaching. Evaluations are mostly based on questionnaires completed by residents. We investigated to what extent characteristics of residents, clinical teachers, and the clinical environment influenced these evaluations, and the relation between…

[Local approval procedures act as a brake on RCTs].

PubMed

van der Stok, E P; Huiskens, J; Hemmes, B; Grünhagen, D J; van Gulik, T M; Verhoef, C; Punt, C J A

2016-01-01

Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. Retrospective, descriptive. All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.

Effects of an alert system on implantable cardioverter defibrillator-related anxiety: rationale, design, and endpoints of the PANORAMIC multicentre trial.

PubMed

Duru, Firat; Dorian, Paul; Favale, Stefano; Perings, Christian; Pedersen, Susanne S; Willems, Vincent

2010-05-01

Implantable cardioverter defibrillators (ICD) can prevent sudden cardiac death by delivering high-energy shocks in patients at risk of life-threatening ventricular tachyarrhythmias. Patients may be anxious about receiving inappropriate shocks in case of device or lead system malfunction, or about failing to receive needed therapy for the same reason. New devices include programmable vibrating patient notifiers (PN), which, by warning patients of a possible device dysfunction, might lower device-related anxiety. PAtient NOtifier feature for Reduction of Anxiety: a Multicentre ICD study (PANORAMIC) is a multicentre, randomized, clinical trial designed to examine the effects of the awareness of an active vibrating alert system on device-related anxiety. The trial will randomly assign 356 patients in a 1:1 design to a control group (PN OFF) vs. a treatment group (PN ON). Patients will be followed for 12 months, with visits scheduled at 6 and 12 months. During clinical follow-up visits, the ICD will be interrogated, and all patients will complete the Hospital Anxiety and Depression Scale and a device-related anxiety questionnaire. The sensitivity and specificity of PN, the effect of personality on anxiety, using the Type D scale (DS14), the number of delivered appropriate and inappropriate ICD therapies, changes in anxiety related to the delivery of appropriate or inappropriate shocks, crossovers from the assigned group, the number of hospitalizations, and the mortality rate will also be assessed. ClinicalTrials.gov Identifier: NCT00559559.

The utility of e-Learning to support training for a multicentre bladder online adaptive radiotherapy trial (TROG 10.01-BOLART).

PubMed

Foroudi, Farshad; Pham, Daniel; Bressel, Mathias; Tongs, David; Rolfo, Aldo; Styles, Colin; Gill, Suki; Kron, Tomas

2013-10-01

An e-Learning programme appeared useful for providing training and information regarding a multi-centre image guided radiotherapy trial. The aim of this study is to demonstrate the utility of this e-Learning programme. Modules were created on relevant pelvic anatomy, Cone Beam CT soft tissue recognition and trial details. Radiation therapist participants' knowledge and confidence were evaluated before, at the end of, and after at least 6 weeks of e-Learning (long term). One hundred and eighty-five participants were recruited from 12 centres, with 118 in the first, and 67 in the second cohort. One hundred and forty-six participants had two tests (pre and post e-Learning) and 39 of these had three tests (pre, post, and long term). There was an increase confidence after completion of modules (p<0.001). The first cohort pre scores increased from 67 ± 11 to 79 ± 8 (p<0.001) post. The long term same question score was 73 ± 14 (p=0.025, comparing to pre-test), and different questions' score was 77 ± 13 (p=0.014). In the second cohort, pre-test scores were 64 ± 10, post-test same question score 78 ± 9 (p<0.001) and different questions' score 81 ± 11 (p<0.001). e-Learning for a multi-centre clinical trial was feasible and improved confidence and knowledge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Computerized detection of breast lesions in multi-centre and multi-instrument DCE-MR data using 3D principal component maps and template matching

NASA Astrophysics Data System (ADS)

Ertas, Gokhan; Doran, Simon; Leach, Martin O.

2011-12-01

In this study, we introduce a novel, robust and accurate computerized algorithm based on volumetric principal component maps and template matching that facilitates lesion detection on dynamic contrast-enhanced MR. The study dataset comprises 24 204 contrast-enhanced breast MR images corresponding to 4034 axial slices from 47 women in the UK multi-centre study of MRI screening for breast cancer and categorized as high risk. The scans analysed here were performed on six different models of scanner from three commercial vendors, sited in 13 clinics around the UK. 1952 slices from this dataset, containing 15 benign and 13 malignant lesions, were used for training. The remaining 2082 slices, with 14 benign and 12 malignant lesions, were used for test purposes. To prevent false positives being detected from other tissues and regions of the body, breast volumes are segmented from pre-contrast images using a fast semi-automated algorithm. Principal component analysis is applied to the centred intensity vectors formed from the dynamic contrast-enhanced T1-weighted images of the segmented breasts, followed by automatic thresholding to eliminate fatty tissues and slowly enhancing normal parenchyma and a convolution and filtering process to minimize artefacts from moderately enhanced normal parenchyma and blood vessels. Finally, suspicious lesions are identified through a volumetric sixfold neighbourhood connectivity search and calculation of two morphological features: volume and volumetric eccentricity, to exclude highly enhanced blood vessels, nipples and normal parenchyma and to localize lesions. This provides satisfactory lesion localization. For a detection sensitivity of 100%, the overall false-positive detection rate of the system is 1.02/lesion, 1.17/case and 0.08/slice, comparing favourably with previous studies. This approach may facilitate detection of lesions in multi-centre and multi-instrument dynamic contrast-enhanced breast MR data.

A Retrospective Multicentre Cohort Review of Patient Characteristics and Surgical Aspects versus the Long-Term Outcomes for Recipients of a Fully Implantable Active Middle Ear Implant

PubMed Central

Lefebvre, Philippe P.; Gisbert, Javier; Cuda, Domenico; Tringali, Stéphane; Deveze, Arnaud

2017-01-01

Objective To summarise treatment outcomes compared to surgical and patient variables for a multicentre recipient cohort using a fully implantable active middle ear implant for hearing impairment. To describe the authors' preferred surgical technique to determine microphone placement. Study Design Multicentre retrospective, observational survey. Setting Five tertiary referral centres. Patients Carina recipients (66 ears, 62 subjects) using the current Cochlear® Carina® System or the legacy device, the Otologics® Fully Implantable Middle Ear, with a T2 transducer. Methods Patient file review and routine clinical review. Patient outcomes assessed were satisfaction, daily use and feedback reports at the first fitting and ≥12 months after implantation. Descriptive and statistical analysis of correlations of variables and their influence on outcomes was performed. Independently reported preferred methods for microphone placement are collectively summarised. Results The average implant experience was 3.5 years. Satisfaction increased significantly over time (p < 0.05). No correlation with covariates examined was observed. Feedback significantly decreased over time, showing a significant correlation with microphone location, primary motivation, gender, age at implantation, and contralateral hearing aid use (p < 0.05). Patient satisfaction was inversely correlated with reports of system feedback (p < 0.05). The implantable microphone was most commonly on the posterior inferior mastoid line, in 42/66 (65%) cases, correlating with less likelihood for feedback and consistent with author surgical preference. Conclusion Carina recipients in this study present as satisfied consistent daily users with very few reports of persistent feedback. As microphone location is an influencing factor, a careful surgical consideration of microphone placement is required. The authors prefer a posterior inferior mastoid line position whenever possible. PMID:28052264

The clinical and genetic spectrum of catecholaminergic polymorphic ventricular tachycardia: findings from an international multicentre registry.

PubMed

Roston, Thomas M; Yuchi, Zhiguang; Kannankeril, Prince J; Hathaway, Julie; Vinocur, Jeffrey M; Etheridge, Susan P; Potts, James E; Maginot, Kathleen R; Salerno, Jack C; Cohen, Mitchell I; Hamilton, Robert M; Pflaumer, Andreas; Mohammed, Saira; Kimlicka, Lynn; Kanter, Ronald J; LaPage, Martin J; Collins, Kathryn K; Gebauer, Roman A; Temple, Joel D; Batra, Anjan S; Erickson, Christopher; Miszczak-Knecht, Maria; Kubuš, Peter; Bar-Cohen, Yaniv; Kantoch, Michal; Thomas, Vincent C; Hessling, Gabriele; Anderson, Chris; Young, Ming-Lon; Choi, Sally H J; Cabrera Ortega, Michel; Lau, Yung R; Johnsrude, Christopher L; Fournier, Anne; Van Petegem, Filip; Sanatani, Shubhayan

2018-03-01

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at <19 years of age and their first-degree relatives. Genetic testing was undertaken in 194 of 236 subjects (82%) during 3.5 (1.4-5.3) years of follow-up. The majority (60%) had RyR2-associated CPVT1. Variant locations were predicted based on a 3D structural model of RyR2. Specific residues appear to have key structural importance, supported by an association between cardiac arrest and mutations in the intersubunit interface of the N-terminus, and the S4-S5 linker and helices S5 and S6 of the RyR2 C-terminus. In approximately one quarter of symptomatic patients, cardiac events were precipitated by only normal wakeful activities. This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

The feasibility and cost of a large multicentre audit of process and outcome of prostatectomy.

PubMed Central

Emberton, M; Neal, D E; Black, N; Harrison, M; Fordham, M; McBrien, M P; Williams, R E; McPherson, K; Develin, H B

1995-01-01

Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice. PMID:10156395

Exploring the Use of Actigraphy to Investigate Sleep Problems in Older People with Intellectual Disability

ERIC Educational Resources Information Center

van Dijk, E.; Hilgenkamp, T. I. M.; Evenhuis, H. M.; Echteld, M. A.

2012-01-01

Background: The aim of this study was to explore the use of actigraphy to investigate sleep problems in a convenience sample of clients of Dutch intellectual disability (ID) care providers. Based on data obtained in a large multi-centre study on healthy ageing in people with ID, research questions were: "To what degree are actigraphic…

Ethical approval for research involving geographically dispersed subjects: unsuitability of the UK MREC/LREC system and relevance to uncommon genetic disorders.

PubMed

Lewis, J C; Tomkins, S; Sampson, J R

2001-10-01

To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval.

Behaviour-change intervention in a multicentre, randomised, placebo-controlled COPD study: methodological considerations and implementation.

PubMed

Bourbeau, Jean; Lavoie, Kim L; Sedeno, Maria; De Sousa, Dorothy; Erzen, Damijan; Hamilton, Alan; Maltais, François; Troosters, Thierry; Leidy, Nancy

2016-04-04

Chronic obstructive pulmonary disease is generally progressive and associated with reduced physical activity. Both pharmacological therapy and exercise training can improve exercise capacity; however, these are often not sufficient to change the amount of daily physical activity a patient undertakes. Behaviour-change self-management programmes are designed to address this, including setting motivational goals and providing social support. We present and discuss the necessary methodological considerations when integrating behaviour-change interventions into a multicentre study. PHYSACTO is a 12-week phase IIIb study assessing the effects on exercise capacity and physical activity of once-daily tiotropium+olodaterol 5/5 µg with exercise training, tiotropium+olodaterol 5/5 µg without exercise training, tiotropium 5 µg or placebo, with all pharmacological interventions administered via the Respimat inhaler. Patients in all intervention arms receive a behaviour-change self-management programme to provide an optimal environment for translating improvements in exercise capacity into increases in daily physical activity. To maximise the likelihood of success, special attention is given in the programme to: (1) the Site Case Manager, with careful monitoring of programme delivery; (2) the patient, incorporating patient-evaluation/programme-evaluation measures to guide the Site Case Manager in the self-management intervention; and (3) quality assurance, to help identify and correct any problems or shortcomings in programme delivery and ensure the effectiveness of any corrective steps. This paper documents the comprehensive methods used to optimise and standardise the behaviour-change self-management programme used in the study to facilitate dialogue on the inclusion of this type of programme in multicentre studies. The study has been approved by the relevant Institutional Review Boards, Independent Ethics Committee and Competent Authority according to national and international regulations. The results of this study will be disseminated through relevant, peer-reviewed journals and international conference presentations. NCT02085161. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Acute uncomplicated appendicitis study: rationale and protocol for a multicentre, prospective randomised controlled non-inferiority study to evaluate the safety and effectiveness of non-operative management in children with acute uncomplicated appendicitis.

PubMed

Xu, Jane; Liu, Yingrui Cyril; Adams, Susan; Karpelowsky, Jonathan

2016-12-21

This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. Children who meet the inclusion criteria of an age between 5 and 15 years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30 days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson χ 2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an α level of 0.05. The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. NCT02795793; ACTRN12616000788471. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Correction to: Incidence of severe sepsis and septic shock in German intensive care units: the prospective, multicentre INSEP study.

PubMed

Marx, Gernot

2018-01-01

The members of the SepNet Critical Care Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

[Two HHV8-related illnesses in a HIV-negative patient: Kaposi's sarcoma and multicentric Castleman's disease. Response to treatment with Rituximab and CHOP].

PubMed

Pastor, M A; Vasco, B; Mosquera, J M; Debén, G; Bautista, P; Requena, L

2006-01-01

Human herpes virus 8 (HHV8) was discovered in 1994 in the biopsy of a Kaposi's sarcoma in a patient with AIDS. Since then it has been identified in all variants of Kaposi's sarcoma and in another two rare disorders: multicentric Castleman's disease and primary body-cavity based lymphomas. The case discusses a 68 year old, HIV-negative male patient, presenting Kaposi's sarcoma for one year and being monitored by dermatology, who presented for weakness, anorexia and fever. On examination, he was found to have adenitis of the lymph nodes in his neck, underarm and groin. A biopsy on one of the swellings led to findings characteristic of multicentric plasma cell variant Castleman's disease. Blood tests for HHV8 and HIV were carried out, resulting positive and negative respectively (IgG anti-HHV8 positive, title 1/640, indirect immunofluorescence). PCR amplification showed HHV8 in peripheral blood. Patient received 8 cycles of CHOP and rituximab, leading to complete disappearance of the adenitis and general symptoms, with no worsening of his Kaposi's sarcoma. Patient remained in complete remission for 10 months after treatment. This paper discusses the case of a HIV-, HHV8+ patient, diagnosed with classic Kaposi's sarcoma, who developed multicentric plasma cell variant Castleman's disease. The coincidence of two or more HHV8-related illnesses in a HIV-negative patient has rarely been described in medical literature. Treatment with rituximab combined with CHOP chemotherapy was effective in this case, and no worsening of the patient's KS was observed.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

PubMed

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-12-21

Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). In-depth semi-structured telephone interviews were conducted in 2003-04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

PubMed

Brouwer, O R; Vermeeren, L; van der Ploeg, I M C; Valdés Olmos, R A; Loo, C E; Pereira-Bouda, L M; Smit, F; Neijenhuis, P; Vrouenraets, B C; Sivro-Prndelj, F; Jap-a-Joe, S M; Borgstein, P J; Rutgers, E J Th; Oldenburg, H S A

2012-07-01

To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

PIMS (Positioning In Macular hole Surgery) trial - a multicentre interventional comparative randomised controlled clinical trial comparing face-down positioning, with an inactive face-forward position on the outcome of surgery for large macular holes: study protocol for a randomised controlled trial.

PubMed

Pasu, Saruban; Bunce, Catey; Hooper, Richard; Thomson, Ann; Bainbridge, James

2015-11-17

Idiopathic macular holes are an important cause of blindness. They have an annual incidence of 8 per 100,000 individuals, and prevalence of 0.2 to 3.3 per 1000 individuals with visual impairment. The condition occurs more frequently in adults aged 75 years or older. Macular holes can be repaired by surgery in which the causative tractional forces in the eye are released and a temporary bubble of gas is injected. To promote successful hole closure individuals may be advised to maintain a face-down position for up to 10 days following surgery. The aim of this study is to determine whether advice to position face-down improves the surgical success rate of closure of large (>400 μm) macular holes, and thereby reduces the need for further surgery. This will be a multicentre interventional, comparative randomised controlled clinical trial comparing face-down positioning with face-forward positioning. At the conclusion of standardised surgery across all sites, participants still eligible for inclusion will be allocated randomly 1:1 to 1 of the 2 treatment arms stratified by site, using random permuted blocks of size 4 or 6 in equal proportions. We will recruit 192 participants having surgery for large macular holes (>400 μm); 96 in each of the 2 arms of the study. The primary objective is to determine the impact of face-down positioning on the likelihood of closure of large (≥400 μm) full-thickness macular holes following surgery. This will be the first multicentre randomised control trial to investigate the value of face-down positioning following macular hole standardised surgery. UK CRN: 17966 (date of registration 26 November 2014).

Trauma airway management in emergency departments: a multicentre, prospective, observational study in Japan.

PubMed

Nakao, Shunichiro; Kimura, Akio; Hagiwara, Yusuke; Hasegawa, Kohei

2015-02-04

Although successful airway management is essential for emergency trauma care, comprehensive studies are limited. We sought to characterise current trauma care practice of airway management in the emergency departments (EDs) in Japan. Analysis of data from a prospective, observational, multicentre registry-the Japanese Emergency Airway Network (JEAN) registry. 13 academic and community EDs from different geographic regions across Japan. 723 trauma patients who underwent emergency intubation from March 2010 through August 2012. ED characteristics, patient and operator demographics, methods of airway management, intubation success or failure at each attempt and adverse events. A total of 723 trauma patients who underwent emergency intubation were eligible for the analysis. Traumatic cardiac arrest comprised 32.6% (95% CI 29.3% to 36.1%) of patients. Rapid sequence intubation (RSI) was the initial method chosen in 23.9% (95% CI 21.0% to 27.2%) of all trauma patients and in 35.5% (95% CI 31.4% to 39.9%) of patients without cardiac arrest. Overall, intubation was successful in ≤3 attempts in 96% of patients (95% CI 94.3% to 97.2%). There was a wide variation in the initial methods of intubation; RSI as the initial method was performed in 0-50.9% of all trauma patients among 12 EDs. Similarly, there was a wide variation in success rates and adverse event rates across the EDs. Success rates varied between 35.5% and 90.5% at the first attempt, and 85.1% and 100% within three attempts across the 12 EDs. In this multicentre prospective study in Japan, we observed a high overall success rate in airway management during trauma care. However, the methods of intubation and success rates were highly variable among hospitals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Experience from a multicentre stroke register: a preliminary report

PubMed Central

Hatano, S.

1976-01-01

In collaboration with 15 centres in 10 countries of Africa, Asia, and Europe, WHO started a pilot study of a community-based stroke register, with standardized methods. Preliminary data were obtained on 6395 new cases of stroke in defined study communities, from May 1971 to September 1974. Information on incidence rates, clinical profiles, diagnosis, management, and course and prognosis for these patients is given. PMID:1088404

Magnetic resonance mammography in comparison with mammography in the discovery of multifocal, multicentric and bilateral lesions of breast cancer.

PubMed

Bakhtavar, Khadijeh; Saran, Maryam; Behzadifar, Masoud; Farsi, Maryam

2017-08-01

Breast cancer is one of the health system problems and important diseases that is rising in developing and advanced countries. This study aimed to determine the difference of Magnetic Resonance Mammography (MRM) findings versus mammography in detecting multifocal, multi-centric and malignant bilateral lesions in patients with known breast cancer in Tehran. This cross-sectional study was conducted in Iran and Tehran among breast cancer patients between January 2015 and February 2016. Patients were included in the study prior to surgery, at the request of a surgeon with the aim of detecting multifocal, multi-centric and bilateral lesions. Demographic information was also collected from patients. The results for quantitative variables were expressed as mean and standard deviations, and for qualitative variables, were expressed as relative and absolute frequency. Chi-square test was used to compare the two methods. SPSS Ver.24 (IBM) software was used to analyze the data. Thirty-nine patients were enrolled in the study. The mean age of patients in this study was 48.46±6.836. In mammography, 13 (33.3%) had Composition C and 26 (66.7%) had Composition D according to the type of Composition. In total, 25 patients (89.3%) had one lesion and 3 patients (10.7%) had more than two lesions. In MRM, all lesions observed were mass (54 masses). The number of lesions found in MRM was 27 patients with one lesion (58.9%), 6 patients with two lesions (20.5%) and 5 patients with three lesions (20.6%). MRM detected more lesions compared to mammography (p<0.0001). The value of Chi-square test with a degree of freedom and error level of 0.05 was 3.71 and p<0.0001 that showed a significant relationship between the number of MRM findings in comparison with mammography. The results of our study showed that two or more lesions and bilateral lesions in MRM were more than mammography in women with B Breast Composition C, D; the findings showed that MRM has a better ability to detect breast masses, and can affect the patient's surgical procedure.

Randomized controlled multicentre study comparing biological mesh closure of the pelvic floor with primary perineal wound closure after extralevator abdominoperineal resection for rectal cancer (BIOPEX-study)

PubMed Central

2014-01-01

Background Primary perineal wound closure after conventional abdominoperineal resection (cAPR) for rectal cancer has been the standard of care for many years. Since the introduction of neo-adjuvant radiotherapy and the extralevator APR (eAPR), oncological outcome has been improved, but at the cost of increased rates of perineal wound healing problems and perineal hernia. This has progressively increased the use of biological meshes, although not supported by sufficient evidence. The aim of this study is to determine the effectiveness of pelvic floor reconstruction using a biological mesh after standardized eAPR with neo-adjuvant (chemo)radiotherapy compared to primary perineal wound closure. Methods/Design In this multicentre randomized controlled trial, patients with a clinical diagnosis of primary rectal cancer who are scheduled for eAPR after neo-adjuvant (chemo)radiotherapy will be considered eligible. Exclusion criteria are prior radiotherapy, sacral resection above S4/S5, allergy to pig products or polysorbate, collagen disorders, and severe systemic diseases affecting wound healing, except for diabetes. After informed consent, 104 patients will be randomized between standard care using primary wound closure of the perineum and the experimental arm consisting of suturing a biological mesh derived from porcine dermis in the pelvic floor defect, followed by perineal closure similar to the control arm. Patients will be followed for one year after the intervention and outcome assessors and patients will be blinded for the study treatment. The primary endpoint is the percentage of uncomplicated perineal wound healing, defined as a Southampton wound score of less than II on day 30. Secondary endpoints are hospital stay, incidence of perineal hernia, quality of life, and costs. Discussion The BIOPEX-study is the first randomized controlled multicentre study to determine the additive value of using a biological mesh for perineal wound closure after eAPR with neo-adjuvant radiotherapy compared to primary perineal wound closure with regard to perineal wound healing and the occurrence of perineal hernia. Trail registration number NCT01927497 (Clinicaltrial.gov). PMID:25163547

Asparaginase and MOPP treatment of dogs with lymphoma.

PubMed

Brodsky, E M; Maudlin, G N; Lachowicz, J L; Post, G S

2009-01-01

Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success. To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP). Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement. The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications. L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP.

Management of renal transplant urolithiasis: a multicentre study by the French Urology Association Transplantation Committee.

PubMed

Branchereau, J; Timsit, M O; Neuzillet, Y; Bessède, T; Thuret, R; Gigante, M; Tillou, X; Codas, R; Boutin, J; Doerfler, A; Sallusto, F; Culty, T; Delaporte, V; Brichart, N; Barrou, B; Salomon, L; Karam, G; Rigaud, J; Badet, L; Kleinklauss, F

2018-01-01

Urolithiasis is rare among renal transplant recipients and its management has not been clearly defined. This multicentre retrospective study was organised by the Comité de Transplantation de l'Association Française d'Urologie (French Urology Association transplantation committee). Statistical analysis was performed with SPSS 19 software. Ninety-five patients were included in this study. Renal transplant urolithiasis was an incidental finding in 55% of cases, mostly on a routine follow-up ultrasound examination. One half of symptomatic stones were due to urinary tract infection and the other half were due to an episode of acute renal failure. The initial management following diagnosis of urolithiasis was double J stenting (27%), nephrostomy tube placement (21%), or watchful waiting (52%). Definitive management consisted of: watchful waiting (48%), extracorporeal lithotripsy (13%), rigid or flexible ureteroscopy (26%), percutaneous nephrolithotomy (11%) and surgical pyelotomy (2%). All transplants remained functional following treatment of the stone. The main limitation is the retrospective design. The incidence of lithiasis could be higher in kidney transplanted patients due to a possible anatomical or metabolical abnormalities. The therapeutic management of renal transplant urolithiasis appears to be comparable to that of native kidney urolithiasis.

Multicentre study of allergic contact cheilitis from toothpastes.

PubMed

Francalanci, S; Sertoli, A; Giorgini, S; Pigatto, P; Santucci, B; Valsecchi, R

2000-10-01

The present work reports the results of a multicentre study of toothpaste allergic contact cheilitis (TACC) conducted by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). The study examined 54 patients with eczematous lesions on the lips, the possible cause of which was suspected to be the use of toothpastes. Patch tests were conducted with a standard series, a specially-targeted series (toothpaste cheilitis series, TCS), and with suspected toothpaste(s). A stop-restart test (SRT) was carried out with these, together with a use test to identify possible alternative products. The TCS produced 17 positive reactions in 13 patients, the most frequent being to spearmint oil. Of the 54 patients, 5 displayed positive reactions only to the TCS. The patch tests with toothpaste produced positive reactions in 11/32 patients, the SRT a positive response in 10/12 cases. The diagnosis of TACC was confirmed in 15/54 patients. Alternative products were identified for 5 patients. In conclusion, the allergens most frequently responsible for TACC were the flavourings, and the additional series proved to be useful in many cases (together with patch tests with toothpastes and the SRT) for correct diagnosis and to initiate effective prevention.

The frequency of occurrence and nature of recombinant feline leukemia viruses in the induction of multicentric lymphoma by infection of the domestic cat with FeLV-945.

PubMed

Ahmad, Shamim; Levy, Laura S

2010-08-01

During feline leukemia virus (FeLV) infection in the domestic cat, viruses with a novel envelope gene arise by recombination between endogenous FeLV-related elements and the exogenous infecting species. These recombinant viruses (FeLV-B) are of uncertain disease association, but have been linked to the induction of thymic lymphoma. To assess the role of FeLV-B in the induction of multicentric lymphoma and other non-T-cell disease, the frequency of occurrence and nature of FeLV-B were examined in diseased tissues from a large collection of FeLV-infected animals. Diseased tissues were examined by Southern blot and PCR amplification to detect the presence of FeLV-B. Further analysis was performed to establish the recombination junctions and infectivity of FeLV-B in diseased tissues. The results confirmed the frequent association of FeLV-B with thymic lymphoma but showed infrequent generation, low levels and lack of infectivity of FeLV-B in non-T-cell diseases including multicentric lymphoma.

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

Calculating the risk of a pancreatic fistula after a pancreaticoduodenectomy: a systematic review

PubMed Central

Vallance, Abigail E; Young, Alastair L; Macutkiewicz, Christian; Roberts, Keith J; Smith, Andrew M

2015-01-01

Background A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality. Method An electronic search was performed of Medline (1946–2014) and EMBASE (1996–2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool. Results Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16–50). Conclusion These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed. PMID:26456948

Videoconferencing for site initiations in clinical studies: Mixed methods evaluation of usability, acceptability, and impact on recruitment.

PubMed

Randell, Rebecca; Backhouse, Michael R; Nelson, E Andrea

2016-12-01

A critical issue for multicentre clinical studies is conducting site initiations, ensuring sites are trained in study procedures and comply with relevant governance requirements before they begin recruiting patients. How technology can support site initiations has not previously been explored. This study sought to evaluate use of off-the-shelf web-based videoconferencing to deliver site initiations for a large national multicentre study. Participants in the initiations, including podiatrists, diabetologists, trial coordinators, and research nurses, completed an online questionnaire based on the System Usability Scale (SUS) (N = 15). This was followed by semi-structured interviews, with a consultant diabetologist, a trial coordinator, and three research nurses, exploring perceived benefits and limitations of videoconferencing. The mean SUS score for the videoconferencing platform was 87.2 (SD = 13.7), suggesting a good level of usability. Interview participants perceived initiations delivered by videoconferencing as being more interactive and easier to follow than those delivered by teleconference. In comparison to face-to-face initiations, videoconferencing takes less time, easily fitting in with the work of staff at the local sites. Perceptions of impact on communication varied according to the hardware used. Off-the-shelf videoconferencing is a viable alternative to face-to-face site initiations and confers advantages over teleconferencing.

Acceptability of the female condom in different groups of women in South Africa--a multicentred study to inform the national female condom introductory strategy.

PubMed

Beksinska, M E; Rees, V H; McIntyre, J A; Wilkinson, D

2001-08-01

To assess the acceptability of the female condom to different groups of women and their partners in South Africa. Descriptive, cross-sectional study. Multicentre study conducted in five sites. The study recruited 678 women from five centres to an acceptability trial of the female condom. Acceptability and successful use varied between the centres. Factors affecting successful use and willingness and intention to use the method again. In total, 209 women used the condom at least once. Discontinuation rates were high, with partner reluctance to try the method as the main reason given for discontinuation at all sites. Women who had previous experience with the male condom or who received a more intensive training session generally found the device easier to use. The main issues concerning women were over-lubrication (27%) and concern that the device was too large (28%). The majority of women said that they would be interested in using the method again (86%) and would recommend it to friends (95%). Overcoming partner opposition is an important issue to address when introducing the method. The study was used to address the national introductory strategy of the female condom, which began in 1998.

Geriatric assessment of older patients with cancer in Australia--a multicentre audit.

PubMed

Lakhanpal, Roopa; Yoong, Jaclyn; Joshi, Sachin; Yip, Desmond; Mileshkin, Linda; Marx, Gavin M; Dunlop, Tracey; Hovey, Elizabeth J; Della Fiorentina, Stephen A; Venkateswaran, Lakshmi; Tattersall, Martin H N; Liew, Sem; Field, Kathryn; Singhal, Nimit; Steer, Christopher B

2015-05-01

The aim of this study is to determine the frequency of geriatric assessment in patients aged over 70 years in Australian medical oncology clinics. This was a multicentre audit in two parts: a retrospective file review of initial consultations with an oncologist and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Data was collected at six oncology centres in Victoria, NSW and Canberra from October 2009 to March 2010. Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age was 76 years (range 70-95). The geriatric assessment (GA) domains most frequently assessed during an initial consultation were the presence of comorbidities (92%), social situation-living alone or with someone (80%), social supports (63%), any mention of at least one Activity of Daily Living (ADL) (50%) and performance status (49%). Less frequently assessed were any Instrumental Activity of Daily Living (IADL) (26%), presence of a geriatric syndrome (24%), polypharmacy (29%) and creatinine clearance (11%). Only one patient had all components of ADLs and IADLs assessed. During MDMs all the geriatric domains were comparatively less frequently assessed. No patients had all ADL and IADL components discussed formally in an MDM. This is the first multicentre audit that reveals the low rates of GA in Australian medical oncology practice and describes the GA domains considered important by oncology clinicians. Copyright © 2015 Elsevier Inc. All rights reserved.

Statistical analysis plan for the Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre randomised controlled trial.

PubMed

Vickerstaff, Victoria; Ambler, Gareth; Bunce, Catey; Xing, Wen; Gazzard, Gus

2015-11-11

The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment ('Laser-1st') leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment ('Medicine-1st') and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223 .

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

PubMed

Jörres, A; Gahl, G M; Dobis, C; Polenakovic, M H; Cakalaroski, K; Rutkowski, B; Kisielnicka, E; Krieter, D H; Rumpf, K W; Guenther, C; Gaus, W; Hoegel, J

1999-10-16

There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration.

PubMed

Chalmers, James D; Crichton, Megan; Goeminne, Pieter C; Loebinger, Michael R; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-09-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years.

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

PubMed Central

Crichton, Megan; Goeminne, Pieter C.; Loebinger, Michael R.; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja ; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-01-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. Educational aims To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areas To understand some of the key features of successful disease registries To review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 years To understand the key research priorities identified by EMBARC for the next 5 years PMID:28894479

The effects of added sulphur amino acids, threonine and an ideal amino acid ratio on nitrogen metabolism in mature, overweight dogs.

PubMed

Bohaty, Robin E; de Godoy, Maria R C; McLeod, Kyle R; Harmon, David L

2012-02-01

The objectives of this study were to investigate the effects of added essential amino acids in conjunction with a dietary lysine/MJ of 0.72 on nitrogen (N) metabolism in dogs. Treatments were; a control diet, a diet that provided an ideal amino acid profile (IAA), a diet with added total sulphur amino acids (TSAA), and a diet with added TSAA and threonine (TT). Diets were fed to eight overweight, mature, female hounds using a replicated 4 x 4 Latin Square design. Food intake was similar across treatments, however, food N intake was higher (p < 0.001) for TSAA than control, IAA or TT. Nitrogen absorbed was higher (p < 0.01) for TSAA than IAA and control. Urea N excretion was greater for control than TT (p < 0.05). Urine N excretion did not differ between diets. There were no differences in digestibility or N retention of diets. There were no differences in protein turnover, synthesis, or degradation. Blood metabolites were within normal ranges and did not differ due to dietary treatment. Based on the measurements made in this study, there is no benefit for added TSAA, TT or additional EAA in diets for mature dogs formulated to provide a 0.72 g lysine/MJ ME ratio.

Reappraisal of known malaria resistance loci in a large multi-centre study

PubMed Central

Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

2015-01-01

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. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, 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 anaemia. 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. PMID:25261933

Meeting the privacy requirements for the development of a multi-centre patient registry in Canada: the Rick Hansen Spinal Cord Injury Registry.

PubMed

Noonan, Vanessa K; Thorogood, Nancy P; Joshi, Phalgun B; Fehlings, Michael G; Craven, B Catharine; Linassi, Gary; Fourney, Daryl R; Kwon, Brian K; Bailey, Christopher S; Tsai, Eve C; Drew, Brian M; Ahn, Henry; Tsui, Deborah; Dvorak, Marcel F

2013-05-01

Privacy legislation addresses concerns regarding the privacy of personal information; however, its interpretation by research ethics boards has resulted in significant challenges to the collection, management, use and disclosure of personal health information for multi-centre research studies. This paper describes the strategy used to develop the national Rick Hansen Spinal Cord Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked against best practices. An analysis of the regional and national privacy legislation was conducted to determine the requirements for each of the 31 local RHSCIR sites and the national RHSCIR office. A national privacy and security framework was created for RHSCIR that includes a governance structure, standard operating procedures, training processes, physical and technical security and privacy impact assessments. The framework meets a high-water mark in ensuring privacy and security of personal health information nationally and may assist in the development of other national or international research initiatives. Copyright © 2013 Longwoods Publishing.

Meeting the Privacy Requirements for the Development of a Multi-Centre Patient Registry in Canada: The Rick Hansen Spinal Cord Injury Registry

PubMed Central

Noonan, Vanessa K.; Thorogood, Nancy P.; Joshi, Phalgun B.; Fehlings, Michael G.; Craven, B. Catharine; Linassi, Gary; Fourney, Daryl R.; Kwon, Brian K.; Bailey, Christopher S.; Tsai, Eve C.; Drew, Brian M.; Ahn, Henry; Tsui, Deborah; Dvorak, Marcel F.

2013-01-01

Privacy legislation addresses concerns regarding the privacy of personal information; however, its interpretation by research ethics boards has resulted in significant challenges to the collection, management, use and disclosure of personal health information for multi-centre research studies. This paper describes the strategy used to develop the national Rick Hansen Spinal Cord Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked against best practices. An analysis of the regional and national privacy legislation was conducted to determine the requirements for each of the 31 local RHSCIR sites and the national RHSCIR office. A national privacy and security framework was created for RHSCIR that includes a governance structure, standard operating procedures, training processes, physical and technical security and privacy impact assessments. The framework meets a high-water mark in ensuring privacy and security of personal health information nationally and may assist in the development of other national or international research initiatives. PMID:23968640

Organic matter and soil structure in the Everglades Agricultural Area

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wright, Alan L.; Hanlon, Edward A.

This publication pertains to management of organic soils (Histosols) in the Everglades Agricultural Area (EAA). These former wetland soils are a major resource for efficient agricultural production and are important globally for their high organic matter content. Recognition of global warming has led to considerable interest in soils as a repository for carbon. Soils rich in organic matter essentially sequester or retain carbon in the profile and can contribute directly to keeping that sequestered carbon from entering the atmosphere. Identification and utilization of management practices that minimize the loss of carbon from organic soils to the atmosphere can minimize effectsmore » on global warming and increase the longevity of subsiding Histosols for agricultural use. Understanding and predicting how these muck soils will respond to current and changing land uses will help to manage soil carbon. The objectives of this document are to: a. Discuss organic soil oxidation relative to storing or releasing carbon and nitrogen b. Evaluate effects of cultivation (compare structure for sugarcane vs. uncultivated soil) Based upon the findings from the land-use comparison (sugarcane or uncultivated), organic carbon was higher with cultivation in the lower depths. There is considerable potential for minimum tillage and residue management to further enhance carbon sequestration in the sugarcane system. Carbon sequestration is improved and soil subsidence is slowed with sugarcane production, and both of these are positive outcomes. Taking action to increase or maintain carbon sequestration appears to be appropriate but may introduce some risk to farming operations. Additional management methods are needed to reduce this risk. For both the longevity of these organic soils and from a global perspective, slowing subsidence through BMP implementation makes sense. Since these BMPs also have considerable societal benefit, it remains to be seen if society will help to offset a part or all of the additional risk through some form of cost-sharing program or carbon credits trading. In general, the subsidence throughout the EAA has been slowed because of higher water table management and implementation of other selected BMPs. In addition, the comparison of soil with different land uses shows that the humification rate, conversion of organic matter from peat to humus, has changed. Another likely factor is a relative increase in the mineral content of soil as the organic constituents are lost through subsidence.« less

Effect of selected fungi on the reduction of gossypol levels and nutritional value during solid substrate fermentation of cottonseed meal*

PubMed Central

Zhang, Wen-ju; Xu, Zi-rong; Sun, Jian-yi; Yang, Xia

2006-01-01

The objective of this work was to investigate the effect of six individual strains of fungi on the reduction of gossypol levels and nutritional value during solid substrate fermentation of cottonseed meal (CSM). Six groups of disinfected CSM substrate were incubated for 48 h after inoculation with either of the fungi C. capsuligena ZD-1, C. tropicalis ZD-3, S. cerevisae ZD-5, A. terricola ZD-6, A. oryzae ZD-7, or A. niger ZD-8. One not inoculated group (substrate) was used as a control. Levels of initial and final free gossypol (FG), crude protein (CP), amino acids (AA) and in vitro digestibility were assayed. The experiment was done in triplicate. The experimental results indicated that microbial fermentation could greatly decrease (P<0.05) FG levels in CSM. The detoxification efficiency differed between the species of microorganisms applied. From the perspective of reducing CSM potential toxicity, C. tropicalis ZD-3 was most successful followed by S. cerevisae ZD-5 and A. niger ZD-8. They could reduce FG levels of CSM to 29.8, 63.07 and 81.50 mg/kg based on DM (dry matter), respectively, and their detoxification rates were 94.57%, 88.51% and 85.16%, respectively. If crude protein, amino acids content and their in vitro digestibility were also taken into account, A. niger ZD-8 may be the best choice. The CP content of CSM substrate fermented by C. tropicalis ZD-3 and A. niger ZD-8 were improved by 10.76% and 22.24%; the TAA (total amino acids) contents were increased by 7.06% and 11.46%, and the EAA (essential amino acids) were raised by 7.77% and 12.64%, respectively. Especially, the levels of methionine, lysine and threonine were improved greatly (P<0.05). The in vitro CP digestibility of CSM fermented by C. tropicalis ZD-3 and A. niger ZD-8 was improved by 13.42% and 18.22%, the TAA were increased by 17.75% and 22.88%, and the EAA by 16.61% and 21.01%, respectively. In addition, the in vitro digestibility of methionine, lysine and threonine was also improved greatly (P<0.05). PMID:16909468

Formation of electrophilic oxidation products from mitochondrial cardiolipin in vitro and in vivo in the context of apoptosis and atherosclerosis.

PubMed

Zhong, Huiqin; Lu, Jianhong; Xia, Lin; Zhu, Mingjiang; Yin, Huiyong

2014-01-01

Emerging evidence indicates that mitochondrial cardiolipins (CL) are prone to free radical oxidation and this process appears to be intimately associated with multiple biological functions of mitochondria. Our previous work demonstrated that a significant amount of potent lipid electrophiles including 4-hydroxy-nonenal (4-HNE) was generated from CL oxidation through a novel chemical mechanism. Here we provide further evidence that a characteristic class of CL oxidation products, epoxyalcohol-aldehyde-CL (EAA-CL), is formed through this novel mechanism in isolated mice liver mitochondria when treated with the pro-apoptotic protein t-Bid to induce cyt c release. Generation of these oxidation products are dose-dependently attenuated by a peroxidase inhibitor acetaminophen (ApAP). Using a mouse model of atherosclerosis, we detected significant amount of these CL oxidation products in liver tissue of low density lipoprotein receptor knockout (LDLR -/-) mice after Western diet feeding. Our studies highlight the importance of lipid electrophiles formation from CL oxidation in the settings of apoptosis and atherosclerosis as inhibition of CL oxidation and lipid electrophiles formation may have potential therapeutic value in diseases linked to oxidant stress and mitochondrial dysfunctions.

Valine Supplementation in a Reduced Protein Diet Regulates Growth Performance Partially through Modulation of Plasma Amino Acids Profile, Metabolic Responses, Endocrine, and Neural Factors in Piglets.

PubMed

Zhang, Xiaoya; Liu, Xutong; Jia, Hongmin; He, Pingli; Mao, Xiangbing; Qiao, Shiyan; Zeng, Xiangfang

2018-03-28

The objective of this study was to investigate whether valine (Val) supplementation in a reduced protein (RP) diet regulates growth performance associated with the changes in plasma amino acids (AAs) profile, metabolism, endocrine, and neural system in piglets. Piglets or piglets with a catheter in the precaval vein were randomly assigned to two treatments, including two RP diets with standardized ileal digestible (SID) Val:Lysine (Lys) ratio of 0.45 and 0.65, respectively. The results indicated that piglets in the higher Val:Lys ratio treatment had higher average daily feed intake (ADFI) ( P < 0.001), average daily gain (ADG) ( P = 0.001), feed conversion ratio (FCR) ( P = 0.004), lower plasma urea nitrogen ( P = 0.032), expression of gastric cholecystokinin (CCK), and hypothalamic pro-opiomelanocortin (POMC). Plasma AAs profiles including postprandial plasma essential AAs (EAAs) profile and in serum, muscle, and liver involved in metabolism of AAs and fatty acids were significantly different between two treatments. In conclusion, Val influenced growth performance associated with metabolism of AAs and fatty acids and both endocrine and neural system in piglets.

Effects of the NMDA receptor antagonist, D-CPPene, on sensitization to the operant decrement produced by naloxone in morphine-treated rats.

PubMed

Bespalov, A Y; Medvedev, I O; Sukhotina, I A; Zvartau, E E

2001-04-01

Sensitization to the rate-decreasing effects of opioid antagonists induced by acute pretreatment with opioid agonists has been suggested to reflect initial changes in opioid systems that underlie physical dependence. Glutamate receptors are implicated in the development and expression of opioid dependence, and antagonists acting at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors have been shown repeatedly to attenuate the severity of opioid withdrawal. The present study evaluated the ability of a competitive NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid), to affect morphine-induced sensitization to naloxone in rats trained to lever-press on a multiple-trial, fixed-ratio 10 schedule of food reinforcement. D-CPPene (0.3-3 mg/kg) was administered either 4 h or 30 min prior to the test session. Morphine (10 mg/kg) or its vehicle was administered 4 h before naloxone challenge (0.3-3 mg/kg). D-CPPene failed to prevent morphine-induced potentiation of the naloxone-produced decrement in operant performance. Thus, these results suggest that agonist-induced sensitization to behavioral effects of opioid antagonists may be insensitive to NMDA receptor blockade.

Critically Ill Patients and End-of-Life Decision-Making: The Senior Medical Resident Experience

ERIC Educational Resources Information Center

Ahern, Stephane P.; Doyle, Tina K.; Marquis, Francois; Lesk, Corey; Skrobik, Yoanna

2012-01-01

In order to improve the understanding of educational needs among residents caring for the critically ill, narrative accounts of 19 senior physician trainees participating in level of care decision-making were analyzed. In this multicentre qualitative study involving 9 university centers in Canada, in-depth interviews were conducted in either…

Psychological Problems in Children with Cerebral Palsy: A Cross-Sectional European Study

ERIC Educational Resources Information Center

Parkes, Jackie; White-Koning, Melanie; Dickinson, Heather O.; Thyen, Ute; Arnaud, Catherine; Beckung, Eva; Fauconnier, Jerome; Marcelli, Marco; McManus, Vicki; Michelsen, Susan I.; Parkinson, Kathryn; Colver, Allan

2008-01-01

Objectives: To describe psychological symptoms in 8-12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family. Design: A cross-sectional multi-centre survey. Participants: Eight hundred and eighteen children with cerebral palsy, aged 8-12 years, identified from population-based…

Foetal Antiepileptic Drug Exposure and Verbal versus Non-Verbal Abilities at Three Years of Age

ERIC Educational Resources Information Center

Meador, Kimford J.; Baker, Gus A.; Browning, Nancy; Cohen, Morris J.; Clayton-Smith, Jill; Kalayjian, Laura A.; Kanner, Andres; Liporace, Joyce D.; Pennell, Page B.; Privitera, Michael; Loring, David W.

2011-01-01

We previously reported that foetal valproate exposure impairs intelligence quotient. In this follow-up investigation, we examined dose-related effects of foetal antiepileptic drug exposure on verbal and non-verbal cognitive measures. This investigation is an ongoing prospective observational multi-centre study in the USA and UK, which has enrolled…

Cut-off of anthropometry measurement and nutritional status among elderly outpatient in Indonesia: multi-centre study.

PubMed

Setiati, Siti; Istanti, Rahmi; Andayani, Rejeki; Kuswardhani, R A Tuty; Aryana, I G P Suka; Putu, I Dewa; Apandi, M; Ichwani, Jusri; Soewoto, Sumarmi; Dinda, Rose; Mustika, Syifa

2010-10-01

To obtain the cut-off value of anthropometric measurements and nutritional status of elderly in Indonesia. A multicentre-cross sectional study was performed at 9 hospitals in Indonesia. The data collected comprises of samples characteristics, anthropometric measurements (weight, height, trisep, bisep, subscapular, suprailiac, and circumference of the hip, waist, arm, calf, and thigh), albumin value, MNA score and ADL Index of Barthel. A total of 702 subjects were collected. The average value of serum albumin is 4.28 g/dl, with 98% subjects had normal serum albumin (> 3.5 g/dl). The mean MNA score and BMI was 23.07 and 22.54 respectively. Most of subjects (56.70%) had risk of malnutrition based on MNA score, and 45.01% had normal nutritional status based on body mass index. Average value of several anthropometric measures (weight, stature, and body mass index; sub-scapular and supra-iliac skinfolds; thigh, calf, mid-arm, and waist circumferences) in various age groups in both groups of women and men were obtained. Cut-off values of various anthropometric indicators were also analyzed in this study with MNA as a gold standard. This study showed age related anthropometric measurement differences in both men and women aged 60 years and older.

Does item overlap render measured relationships between pain and challenging behaviour trivial? Results from a multicentre cross-sectional study in 13 German nursing homes.

PubMed

Kutschar, Patrick; Bauer, Zsuzsa; Gnass, Irmela; Osterbrink, Jürgen

2017-07-01

Several studies suggest that pain is a trigger for challenging behaviour in older adults with cognitive impairment. However, such measured relationships might be confounded due to item overlap as instruments share similar or identical items. The purpose of this study was to examine whether the frequently observed association between pain and challenging behaviour might be traced back to item overlap. This multicentre cross-sectional study was conducted in 13 nursing homes and examined pain (measure: Pain Assessment in Advanced Dementia Scale) and challenging behaviour (measure: Cohen-Mansfield Agitation Inventory) in 150 residents with severe cognitive impairment. The extent of item overlap was determined by juxtaposition of both measures' original items. As expected, comparison between these instruments revealed an extensive item overlap. The statistical relationship between the two phenomena can be traced back mainly to the contribution of the overlapping items, which renders the frequently stated relationship between pain and challenging behaviour trivial. The status quo of measuring such associations must be contested: constructs' discrimination and instruments' discrimination have to be discussed critically as item overlap may lead to biased conclusions and assumptions in research as well as to inadequate care measures in nursing practice. © 2017 John Wiley & Sons Ltd.

The effectiveness of influenza vaccination in preventing hospitalisations of elderly individuals in two influenza seasons: a multicentre case-control study, Spain, 2013/14 and 2014/15.

PubMed

Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Espejo, Elena; Fernandez, Maria Amelia; Mayoral, José María; Castilla, Jesús; Egurrola, Mikel; Tamames, Sonia; Astray, Jenaro; Morales-Suárez-Varela, María

2017-08-24

Influenza vaccination may limit the impact of influenza in the community. The aim of this study was to assess the effectiveness of influenza vaccination in preventing hospitalisation in individuals aged ≥ 65 years in Spain. A multicentre case-control study was conducted in 20 Spanish hospitals during 2013/14 and 2014/15. Patients aged ≥ 65 years who were hospitalised with laboratory-confirmed influenza were matched with controls according to sex, age and date of hospitalisation. Adjusted vaccine effectiveness (VE) was calculated by multivariate conditional logistic regression. A total of 728 cases and 1,826 matched controls were included in the study. Overall VE was 36% (95% confidence interval (CI): 22-47). VE was 51% (95% CI: 15-71) in patients without high-risk medical conditions and 30% (95% CI: 14-44) in patients with them. VE was 39% (95% CI: 20-53) in patients aged 65-79 years and 34% (95% CI: 11-51) in patients aged ≥ 80 years, and was greater against the influenza A(H1N1)pdm09 subtype than the A(H3N2) subtype. Influenza vaccination was effective in preventing hospitalisations of elderly individuals. This article is copyright of The Authors, 2017.

Ethical approval for research involving geographically dispersed subjects: unsuitability of the UK MREC/LREC system and relevance to uncommon genetic disorders

PubMed Central

Lewis, J C; Tomkins, S; Sampson, J R

2001-01-01

Objectives—To assess the process involved in obtaining ethical approval for a single-centre study involving geographically dispersed subjects with an uncommon genetic disorder. Design—Observational data of the application process to 53 local research ethics committees (LRECs) throughout Wales, England and Scotland. The Multicentre Research Ethics Committee (MREC) for Wales had already granted approval. Results—Application to the 53 LRECs required 24,552 sheets of paper and took two months of the researcher's time. The median time taken for approval was 39 days with only seven (13%) of committees responding within the recommended 21 days. In at least nineteen cases (36%) a subcommittee considered the application. Thirty-three committees (62%) accepted the proposal without amendments but, of the remainder, four (8%) requested changes outside of the remit of LRECs. Discussion—Difficulties still exist with the system for obtaining ethical approval for studies involving a single centre but with patients at multiple sites, as is often required for genetic observational research. As such studies differ from true multicentre studies, it may be advantageous to develop a separate and specific process of application to ensure that resources are not unnecessarily expended in the quest for ethical approval. Key Words: Research ethics • MREC • LREC PMID:11579194

[Sonographically detectable splenic disorders in dogs with malignant lymphoma].

PubMed

Eberhardt, F; Köhler, C; Krastel, D; Winter, K; Alef, M; Kiefer, I

2015-01-01

To evaluate the frequency of different sonographic splenic disorders in dogs with different anatomic forms of malignant lymphoma. Additionally, the occurrence of the moth-eaten pattern in the parenchyma of the spleen in patients with diseases other than lymphoma should be investigated. Retrospective analysis of patient data collected from dogs histologically or cytologically diagnosed with malignant lymphoma and for which ultrasonographic images were available before the initiation of therapy. Patient data from dogs with a moth-eaten pattern within the splenic parenchyma were evaluated separately. Exclusion criterion was the administration of cytostatic agents prior to diagnosis. In 84% of 164 dogs with malignant lymphoma, an altered pattern of the spleen was diagnosed ultrasonographically. Ninety-four of these 137 patients had a moth-eaten pattern of the splenic parenchyma and 43 dogs displayed abnormalities in the form of splenomegaly, coarse echotexture or other changes of the parenchyma. When a moth-eaten pattern was diagnosed, the affected dogs suffered significantly more often from a multicentric lymphoma (95%) than from any other anatomical lymphoma form. Only one dog displayed a moth-eaten pattern of the splenic parenchyma without diagnosis of a malignant lymphoma. The positive predictive value of the moth-eaten pattern for malignant lymphoma was 99% and, in particular, for the multicentric lymphoma this was 95%. In total, 84% of the 164 dogs displayed a multicentric lymphoma, 5% a mediastinal or a cutaneous lymphoma, respectively, 4% a gastrointestinal lymphoma, and one animal had an ocular or renal lymphoma, respectively. Sonographic changes of the spleen are often diagnosed in dogs with malignant lymphoma, independent of the anatomical lymphoma form. When the moth-eaten pattern is observed, it is very likely that the affected dog suffers from a malignant lymphoma, most probably a multicentric lymphoma.

Dietary protein reduction on microbial protein, amino acid digestibility, and body retention in beef cattle: 2. Amino acid intestinal absorption and their efficiency for whole-body deposition.

PubMed

Mariz, L D S; Amaral, P M; Valadares Filho, S C; Santos, S A; Detmann, E; Marcondes, M I; Pereira, J M V; Silva Júnior, J M; Prados, L F; Faciola, A P

2018-03-06

The objective of this study was to determine the apparent and true intestinal digestibility of total and individual AA, and to estimate the efficiency of whole-body AA retention from individual and total absorbed AA. Four Nellore animals (241.3 kg initial BW) and four crossbred Angus × Nellore (263.4 kg initial BW) cannulated in rumen and ileum were randomly allocated in two 4 × 4 Latin squares. The experiment lasted four 17 d periods, with 10 d for adaptation to diets and another 7 d for data collection. The diets consisted of increasing CP levels: 100, 120, or 140 g/kg of DM offered ad libitum, and restricted intake diet with 120 g CP/kg DM (experiment 1). In experiment 2, forty-four bulls (22 Nellore and 22 crossbred F1 Angus × Nellore) with 8 months and initial shrunk BW 215.0 ± 15.0 kg (Nellore = 208.0 ± 12.78 kg; Angus × Nellore = 221.9 ± 14.16 kg) were used. Eight of those animals were slaughtered at the beginning of the experiment. The remaining 36 bulls were allocated in a completely randomized design with six replicates, in a 2 (genetic groups) × 3 (CP contents) factorial scheme. The amount of essential AA (EAA) and nonessential AA (NEAA) reaching the small intestine increased linearly (P < 0.05) in response to CP content. The apparent digestibility of EAA was not affected (P > 0.05) by CP content, with exception for histidine (P = 0.07, linear effect), leucine (P = 0.01, linear effect), and methionine (P = 0.05, linear effect). Differences existed among AA when compared the apparent digestibility of NEAA. The apparent digestibility of alanine (P = 0.05), aspartic acid (P = 0.07), glutamic acid (P = 0.02), glycine (P = 0.05), proline (P = 0.02), and serine (P = 0.04) responded quadratically to CP content increase. However, the apparent digestibility of cystine and tyrosine was not affected (P > 0.05) by increasing dietary CP. The true intestinal digestibilities of total, essential, nonessential AA, lysine, and methionine were 75.0%, 77.0%, 74.0%, 77.0%, and 86%, respectively. The true intestinal digestibility of total microbial AA was 80%. The efficiency of utilization of total AA for whole-body protein deposition was 40%. The efficiency of utilization of lysine and methionine was 37% and 58%, respectively. It was concluded that the AA flow to the omasum increases in response to dietary CP content. In addition, there are differences among AA in the efficiency that they are used by beef cattle.

Nocturnal emergency department visits, duration of symptoms and risk of hospitalisation among adults with asthma exacerbations: a multicentre observational study.

PubMed

Yasuda, Hideto; Hagiwara, Yusuke; Watase, Hiroko; Hasegawa, Kohei

2016-08-12

We sought to compare the characteristics of patients with asthma presenting to the emergency department (ED) during the night-time with those of patients presenting at other times of the day, and to determine whether the time of ED presentation is associated with the risk of hospitalisation. A multicentre chart review study of 23 EDs across Japan. Patients aged 18-54 years with a history of physician-diagnosed asthma, presented to the ED between January 2009 and December 2011 OUTCOME MEASURES: The outcome of interest was hospitalisation, including admissions to an observation unit, inpatient unit and intensive care unit. Among the 1354 patients (30.1% in the night-time group vs 69.9% in the other time group) included in this study, the median age was 34 years and ∼40% were male. Overall 145 patients (10.7%) were hospitalised. Patients in the night-time group were more likely to have a shorter duration of symptoms (≤3 hours) before ED presentation than those in the other time group (25.9% in night-time vs 13.4% in other times; p<0.001). In contrast, there were no significant differences in respiratory rate, initial peak expiratory flow or ED asthma treatment between the two groups (p>0.05). Similarly, the risk of hospitalisation did not differ between the two groups (11.3% in night-time vs 10.5% in other times; p=0.65). In a multivariable model adjusting for potential confounders, the risk of hospitalisation in the night-time group was not statistically different from the other time group (OR, 1.10; 95% CI 0.74 to 1.61; p=0.63). This multicentre study in Japan demonstrated no significant difference in the risk of hospitalisations according to the time of ED presentation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

PubMed

Mohanty, D; Colah, R B; Gorakshakar, A C; Patel, R Z; Master, D C; Mahanta, J; Sharma, S K; Chaudhari, U; Ghosh, M; Das, S; Britt, R P; Singh, S; Ross, C; Jagannathan, L; Kaul, R; Shukla, D K; Muthuswamy, V

2013-01-01

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for β-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for β-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

A Multidisciplinary Evaluation of a Web-based eLearning Training Programme for SAFRON II (TROG 13.01): a Multicentre Randomised Study of Stereotactic Radiotherapy for Lung Metastases.

PubMed

Pham, D; Hardcastle, N; Foroudi, F; Kron, T; Bressel, M; Hilder, B; Chesson, B; Oates, R; Montgomery, R; Ball, D; Siva, S

2016-09-01

In technically advanced multicentre clinical trials, participating centres can benefit from a credentialing programme before participating in the trial. Education of staff in participating centres is an important aspect of a successful clinical trial. In the multicentre study of fractionated versus single fraction stereotactic ablative body radiotherapy in lung oligometastases (TROG 13.01), knowledge transfer of stereotactic ablative body radiotherapy techniques to the local multidisciplinary team is intended as part of the credentialing process. In this study, a web-based learning platform was developed to provide education and training for the multidisciplinary trial teams at geographically distinct sites. A web-based platform using eLearning software consisting of seven training modules was developed. These modules were based on extracranial stereotactic theory covering the following discrete modules: Clinical background; Planning technique and evaluation; Planning optimisation; Four-dimensional computed tomography simulation; Patient-specific quality assurance; Cone beam computed tomography and image guidance; Contouring organs at risk. Radiation oncologists, medical physicists and radiation therapists from hospitals in Australia and New Zealand were invited to participate in this study. Each discipline was enrolled into a subset of modules (core modules) and was evaluated before and after completing each module. The effectiveness of the eLearning training will be evaluated based on (i) knowledge retention after participation in the web-based training and (ii) confidence evaluation after participation in the training. Evaluation consisted of a knowledge test and confidence evaluation using a Likert scale. In total, 130 participants were enrolled into the eLearning programme: 81 radiation therapists (62.3%), 27 medical physicists (20.8%) and 22 radiation oncologists (16.9%). There was an average absolute improvement of 14% in test score (P < 0.001) after learning. This score improvement compared with initial testing was also observed in the long-term testing (>4 weeks) after completing the modules (P < 0.001). For most there was significant increase in confidence (P < 0.001) after completing all the modules. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns

PubMed Central

2011-01-01

Background The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities). A particular focus was on the effects of the study design and the diagnostic procedure on the homogeneity of the sample in terms of symptom-based behavioural data, and potential consequences for further analyses based on these data. Methods Diagnosis was based on the Parental Account of Childhood Symptoms (PACS) interview and the DSM-IV items of the Conners' teacher questionnaire. Demographics of the full sample and the homogeneity of a subsample (all probands) were analysed by using robust statistical procedures which were adjusted for unequal sample sizes and skewed distributions. These procedures included multi-way analyses based on trimmed means and winsorised variances as well as bootstrapping. Results Age and proband/sibling ratios differed between participating centres. There was no significant difference in the distribution of gender between centres. There was a significant interaction between age and centre for number of inattentive, but not number of hyperactive symptoms. Higher ADHD symptom frequencies were reported by parents than teachers. The diagnostic symptoms differed from each other in their frequencies. The face-to-face interview was more sensitive than the questionnaire. The differentiation between ADHD-CT probands and unaffected siblings was mainly due to differences in hyperactive/impulsive symptoms. Conclusions Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, centres may differ markedly in probands' ADHD symptom frequencies. Both the diagnostic procedure and the multi-centre design influence the behavioural characteristics of a sample and, thus, may bias statistical analyses, particularly in genetic or neurobehavioral studies. PMID:21473745

Role of Obesity Variables in Detecting Hypertension in an Iranian Population.

PubMed

Khashayar, Patricia; Aghaei Meybodi, Hamidreza; Rezaei Hemami, Mohsen; Larijani, Bagher

2017-09-01

As the high incidence of hypertension has been in conjunction with dramatic increase in the prevalence of obesity, many studies have suggested obesity as its underlying cause in diverse race and ethnic groups. The present study was designed to quantify the relationship between obesity variables and hypertension in Iranian population. A ROC curve analysis was also used to determine an optimal BMI cutoff for obesity with the aim of representing elevated incidence of hypertension in this population. The study population comprised of apparently healthy men and women who participated in the Iranian Multi-centric Osteoporosis Studies (IMOS), a multi-centric cross-sectional study carried out in urban areas of five great cities (Tehran, Tabriz, Mashhad, Shiraz and Bushehr). The anthropometric (weight, height, waist and hip circumferences) and blood pressure measures were reported in some 5724 subjects. The influence of these factors on systolic and diastolic blood pressure was assessed based on a list-wise method. There was a significant difference in the studied subjects anthropometric (weight classes (BMI), WC and HC, and WHR) and blood pressure variables; age, gender and weight, however, were the only factors significantly influencing SBP and DBP. Furthermore, BMI showed a significant impact on the overall risk of developing hypertension. General obesity rather than abdominal obesity is directly linked with higher blood pressure levels in Iranian population.

Czech multicenter research database of severe COPD

PubMed Central

Novotna, Barbora; Koblizek, Vladimir; Zatloukal, Jaromir; Plutinsky, Marek; Hejduk, Karel; Zbozinkova, Zuzana; Jarkovsky, Jiri; Sobotik, Ondrej; Dvorak, Tomas; Safranek, Petr

2014-01-01

Purpose Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. Patients and methods The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. Results The objective of this paper was to outline the methodology of this study. Conclusion The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic. PMID:25419124

Multicentric Fibrosarcoma in a Cat and a Review of the Literature

PubMed Central

Harasen, G. L. G.

1984-01-01

A case of multicentric fibrosarcoma in a ten month old domestic short-haired cat is presented and discussed. Tumor tissue was found to involve the right distal forepaw, right shoulder area and a popliteal lymph node. This anaplastic neoplasm was concentrated primarily in subcutaneous tissues but also extended to muscle, bone and lung. The cat was found to be positive for feline leukemia virus by the ELISA test. Based on these findings, it is likely that the lesions in this case result from an interaction between the feline leukemia virus and feline sarcoma virus. ImagesFigures 1 and 2.Figure 3.Figure 4. PMID:17422403

Corruption and research.

PubMed

Luna, Florencia

1999-07-01

Last year there was a heated debate regarding clinical trials with AZT carried out in developing countries. AIDS vaccine trials also posed various dilemmas and ethical problems. In this paper I will consider the possibility of corruption in bioethics, and international multi-centre research will be taken as an example. International clinical trials will be seen from another perspective. I will try to show that the possibility of systemic corruption should be considered when designing an international multi-centre research trial which may involve countries in very different situations regarding corruption. I will analyze three different approaches to this problem and suggest some strategies regarding their capacity to exclude the possibility of corruption.

Motives and Suicide Intent Underlying Hospital Treated Deliberate Self-Harm and Their Association with Repetition

ERIC Educational Resources Information Center

McAuliffe, Carmel; Arensman, Ella; Keeley, Helen S.; Corcoran, Paul; Fitzgerald, Anthony P.

2007-01-01

The association between motives for deliberate self-harm (DSH), level of suicide intent, and history of DSH is poorly understood. As part of the WHO/EURO Multicentre Study on Suicidal Behavior, the Suicide Intent Scale, and the Motives for Parasuicide Questionnaire were administered to 146 patients presenting with DSH in the Cork region in…

The clinical and cost-benefits of investing in neurobehavioural rehabilitation: a multi-centre study.

PubMed

Oddy, Michael; da Silva Ramos, Sara

2013-01-01

The aim of this study was to investigate the cost-benefits of a residential post-acute neurobehavioural rehabilitation programme and its effects on care needs and social participation of adults with acquired brain injury. Retrospective multi-centre design. Data on occupation, adaptability and level of support required were collected at admission, discharge and 6-months follow-up. Cost analysis was performed on cost estimates based on level of support. Significant gains were observed in all areas of functioning, with individuals progressing towards higher levels of independence and more participation in society upon discharge. Cost-benefits of up to £1.13 million were demonstrated for individuals admitted to rehabilitation within a year of sustaining a brain injury and of up to £0.86 million for those admitted more than 1 year after injury. Functional gains and reductions in levels of care required upon discharge were maintained 6 months later. These results demonstrate that post-acute neurobehavioural rehabilitation can have a positive impact on the lives of individuals with brain injury and that the associated costs are off-set by significant savings in the longer-term.

Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and non-randomized trial.

PubMed

Albert, A; Altabre, C; Baró, F; Buendía, E; Cabero, A; Cancelo, M J; Castelo-Branco, C; Chantre, P; Duran, M; Haya, J; Imbert, P; Julía, D; Lanchares, J L; Llaneza, P; Manubens, M; Miñano, A; Quereda, F; Ribes, C; Vázquez, F

2002-03-01

A multicentric, open, prospective, observational and no-randomized clinical trial was carried out in Spain with 190 postmenopausal women receiving a soy preparation rich in isoflavones (PHYTO SOYA, capsules containing 17.5 mg isoflavones). The main object of the present study was to investigate its efficacy in alleviating the symptomatology derived from the lack of estrogen, mainly hot flushes, but also other symptoms such as sleep disorder, anxiety, depression, vaginal dryness, loss of libido and bone pain. Each patient received 35 mg isoflavones per day in two doses. During the four months' treatment, a statistically significant decrease in the number of hot flushes with PHYTO SOYA was experienced by 80.82% women; only 5,48% patients did not improve with the treatment. The average reduction was 47.8%, which is equivalent to 4 hot flushes. All the other studied parameters also showed a statistically significant decrease. No severe side-effects were reported and tolerance was excellent. Treatment with PHYTO SOYA resulted in a significant improvement of the symptomatology that accompanies the lack of estrogen during menopause.

Efficacy and safety of fluconazole in the treatment of systemic fungal infections in pediatric patients. Multicentre Study Group.

PubMed

Presterl, E; Graninger, W

1994-04-01

In a non-comparative multicentre trial 51 patients aged 24 days to 17 years received treatment with intravenous or oral fluconazole for suspected systemic fungal infections. Twenty-seven patients had confirmed infections, 26 being confirmed mycologically and 1 histologically. All isolates were Candida species. Of the 43 clinically assessed patients, 30 were considered cured, 7 improved and 6 experienced failure of therapy. Of 27 patients with confirmed fungal infections, 25 were assessed mycologically and all but one were considered cured. Of the six patients experiencing clinical failure, two had a confirmed infection and only one of these experienced mycological failure. This patient had a primary diagnosis of candidemia with persistence of Candida albicans and Candida parapsilosis. All 51 patients were evaluable for safety. No treatment-related adverse events required termination of treatment. Treatment-related side effects (diarrhea, vomiting, deafness) were reported by three of 51 patients, three patients had laboratory test abnormalities possibly related to fluconazole treatment, including elevation of liver enzyme levels and of the eosinophil count. Results of this study confirm the efficacy and safety of fluconazole in the treatment of pediatric patients with severe fungal infection.

Outcome of Heart Failure with Preserved Ejection Fraction: A Multicentre Spanish Registry

PubMed Central

Castillo, Juan C; Anguita1, Manuel P; Jiménez, Manuel

2009-01-01

Background: Studies on clinical features, treatment and prognosis of patients with congestive heart failure (CHF) and preserved left ventricular ejection fraction (LVEF) are few and their results frequently conflicting. Aims: To investigate the characteristics and long term prognosis of patients with CHF and preserved (≥ 45%) LVEF. Methods and Results: We conducted a prospective multicentre study with 4720 patients attended in 62 heart failure clinics from 1999 to 2003 in Spain (BADAPIC registry). LVEF was preserved in 30% patients. Age, female gender, prevalence of atrial fibrillation, hypertension and non-ischaemic cardiopathy were all significantly greater in patients with preserved LVEF. Mean follow-up was 40±12 months. Mortality and other cardiovascular complication rates during follow up were similar in both groups. On multivariate analysis ejection fraction was not an independent predictor for mortality. Survival at one and five years was similar in both groups (79% and 59% for patients with preserved LVEF and 78% and 57% for those with reduced LVEF, respectively). Conclusions: In the BADAPIC registry, a high percentage of heart failure patients had preserved LVEF. Although clinical differences were seen between groups, morbidity and mortality were similar in both groups. PMID:21037850

The clinical and cost-benefits of investing in neurobehavioural rehabilitation: A multi-centre study

PubMed Central

Oddy, Michael

2013-01-01

Primary objective The aim of this study was to investigate the cost-benefits of a residential post-acute neurobehavioural rehabilitation programme and its effects on care needs and social participation of adults with acquired brain injury. Research design Retrospective multi-centre design. Methods and procedures Data on occupation, adaptability and level of support required were collected at admission, discharge and 6-months follow-up. Cost analysis was performed on cost estimates based on level of support. Main outcomes and results Significant gains were observed in all areas of functioning, with individuals progressing towards higher levels of independence and more participation in society upon discharge. Conclusions Cost-benefits of up to £1.13 million were demonstrated for individuals admitted to rehabilitation within a year of sustaining a brain injury and of up to £0.86 million for those admitted more than 1 year after injury. Functional gains and reductions in levels of care required upon discharge were maintained 6 months later. These results demonstrate that post-acute neurobehavioural rehabilitation can have a positive impact on the lives of individuals with brain injury and that the associated costs are off-set by significant savings in the longer-term. PMID:24087973

Energy and nutrient intake of patients with mild-to-moderate chronic renal failure compared with healthy children: an Italian multicentre study.

PubMed

Rätsch, I M; Catassi, C; Verrina, E; Gusmano, R; Appiani, A; Bettinelli, A; Picca, S; Rizzoni, G; Fabian-Bach, C; Wingen, A M

1992-09-01

Nutritional counselling is important in the management of children with chronic renal failure (CRF). In 1988, a controlled European multicentre study was started to evaluate the effects of a low-protein diet on the progression of CRF in children. To assess the energy, macro- and micronutrient intake, 4-day weighed dietary records were obtained from 50 children with low to moderate CRF (creatinine clearance 65 to 15 ml/min per 1.73 m2) and from 93 healthy children. The mean energy intake was 90%-93% of the recommended dietary allowance for Italian children in controls and 76%-88% in CRF patients. The mean protein intake was 2.1-3.1 g/kg per day in controls and 1.6-2.7 g/kg per day in CRF patients. Overall, the energy intake was 10% and the protein intake 33% lower in CRF patients than in healthy children. Children with CRF consumed less cholesterol, calcium and phosphorus than healthy children. The lower spontaneous intake of energy, protein and other nutrients should be taken into account when planning the nutrition of children with CRF.

The organisation of physiotherapy for people with multiple sclerosis across Europe: a multicentre questionnaire survey.

PubMed

Rasova, Kamila; Freeman, Jenny; Martinkova, Patricia; Pavlikova, Marketa; Cattaneo, Davide; Jonsdottir, Johanna; Henze, Thomas; Baert, Ilse; Van Asch, Paul; Santoyo, Carme; Smedal, Tori; Beiske, Antonie Giæver; Stachowiak, Małgorzata; Kovalewski, Mariusz; Nedeljkovic, Una; Bakalidou, Daphne; Guerreiro, José Manuel Alves; Nilsagård, Ylva; Dimitrova, Erieta Nikolikj; Habek, Mario; Armutlu, Kadriye; Donzé, Cécile; Ross, Elaine; Ilie, Ana Maria; Martić, Andrej; Romberg, Anders; Feys, Peter

2016-10-06

Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

PubMed Central

2014-01-01

Background Insertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use. Methods/design Overall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted. Discussion The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN49474281. PMID:24383496

Multicentre propensity score-matched analysis of conventional versus extended abdominoperineal excision for low rectal cancer.

PubMed

Ortiz, H; Ciga, M A; Armendariz, P; Kreisler, E; Codina-Cazador, A; Gomez-Barbadillo, J; Garcia-Granero, E; Roig, J V; Biondo, S

2014-06-01

Abdominal perineal excision (APE) was originally described with levator ani removal for rectal cancer. An even wider, more aggressive extralevator resection for APE has been proposed. Although some surgeons are performing a very wide 'extralevator APE (ELAPE)', there are few data to recommend it routinely. This multicentre study aimed to compare outcomes of APE and ELAPE. A multicentre propensity case-matched analysis comparing two surgical approaches (APE and ELAPE) was performed. All patients who underwent abdominoperineal resection of a rectal tumour were considered for the analysis. Tumour height was defined by magnetic resonance imaging measurement and patients with stage II-III tumours had neoadjuvant radiochemotherapy. Involvement of the circumferential resection margin (CRM) and intraoperative tumour perforation were the main outcome measures. A logistic regression model was used to study the relationship between the surgical approaches and outcomes. From January 2008 to March 2013 a total of 1909 consecutive patients underwent APE or ELAPE, of whom 914 matched patients (457 in each group) formed the cohort for analysis. Intraoperative tumour perforation occurred in 7.9 and 7.7 per cent of patients during APE and ELAPE respectively (P = 0.902), and there was CRM involvement in 13.1 and 13.6 per cent (P = 0.846). There were no differences between APE and ELAPE in terms of postoperative complication rates (52.3 versus 48.1 per cent; P = 0.209), need for reoperation (7.7 versus 7.0 per cent; P = 0.703), perineal wound problems (26.0 versus 21.9 per cent; P = 0.141), mortality rate (2.0 versus 2.0 per cent; P = 1.000) and local recurrence rate at 2 years (2.7 versus 5.6 per cent; P = 0.664). ELAPE does not improve rates of CRM involvement, intraoperative tumour perforation, local recurrence or mortality. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

A Comparison of Functional Outcome in Patients Sustaining Major Trauma: A Multicentre, Prospective, International Study

PubMed Central

Rainer, Timothy H.; Yeung, Hiu Hung; Gabbe, Belinda J.; Yuen, Kai Y.; Ho, Hiu F.; Kam, Chak W.; Chang, Annice; Poon, Wai S.; Cameron, Peter A.; Graham, Colin A.

2014-01-01

Objectives To compare 6 month and 12 month health status and functional outcomes between regional major trauma registries in Hong Kong and Victoria, Australia. Summary Background Data Multicentres from trauma registries in Hong Kong and the Victorian State Trauma Registry (VSTR). Methods Multicentre, prospective cohort study. Major trauma patients and aged ≥18 years were included. The main outcome measures were Extended Glasgow Outcome Scale (GOSE) functional outcome and risk-adjusted Short-Form 12 (SF-12) health status at 6 and 12 months after injury. Results 261 cases from Hong Kong and 1955 cases from VSTR were included. Adjusting for age, sex, ISS, comorbid status, injury mechanism and GCS group, the odds of a better functional outcome for Hong Kong patients relative to Victorian patients at six months was 0.88 (95% CI: 0.66, 1.17), and at 12 months was 0.83 (95% CI: 0.60, 1.12). Adjusting for age, gender, ISS, GCS, injury mechanism and comorbid status, Hong Kong patients demonstrated comparable mean PCS-12 scores at 6-months (adjusted mean difference: 1.2, 95% CI: −1.2, 3.6) and 12-months (adjusted mean difference: −0.4, 95% CI: −3.2, 2.4) compared to Victorian patients. Keeping age, gender, ISS, GCS, injury mechanism and comorbid status, there was no difference in the MCS-12 scores of Hong Kong patients compared to Victorian patients at 6-months (adjusted mean difference: 0.4, 95% CI: −2.1, 2.8) or 12-months (adjusted mean difference: 1.8, 95% CI: −0.8, 4.5). Conclusion The unadjusted analyses showed better outcomes for Victorian cases compared to Hong Kong but after adjusting for key confounders, there was no difference in 6-month or 12-month functional outcomes between the jurisdictions. PMID:25157522

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial.

PubMed

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-12-11

Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Randomised multicentre clinical trial. Post hoc analyses of the DASH-Sodium trial in the USA. In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. NCT00000608. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effects of dietary sodium and the DASH diet on the occurrence of headaches: results from randomised multicentre DASH-Sodium clinical trial

PubMed Central

Amer, Muhammad; Woodward, Mark; Appel, Lawrence J

2014-01-01

Objectives Headaches are a common medical problem, yet few studies, particularly trials, have evaluated therapies that might prevent or control headaches. We, thus, investigated the effects on the occurrence of headaches of three levels of dietary sodium intake and two diet patterns (the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat) and a control diet (typical of Western consumption patterns)). Design Randomised multicentre clinical trial. Setting Post hoc analyses of the DASH-Sodium trial in the USA. Participants In a multicentre feeding study with three 30 day periods, 390 participants were randomised to the DASH or control diet. On their assigned diet, participants ate food with high sodium during one period, intermediate sodium during another period and low sodium during another period, in random order. Outcome measures Occurrence and severity of headache were ascertained from self-administered questionnaires, completed at the end of each feeding period. Results The occurrence of headaches was similar in DASH versus control, at high (OR (95% CI)=0.65 (0.37 to 1.12); p=0.12), intermediate (0.57 (0.29 to 1.12); p=0.10) and low (0.64 (0.36 to 1.13); p=0.12) sodium levels. By contrast, there was a lower risk of headache on the low, compared with high, sodium level, both on the control (0.69 (0.49 to 0.99); p=0.05) and DASH (0.69 (0.49 to 0.98); p=0.04) diets. Conclusions A reduced sodium intake was associated with a significantly lower risk of headache, while dietary patterns had no effect on the risk of headaches in adults. Reduced dietary sodium intake offers a novel approach to prevent headaches. Trial registration number NCT00000608. PMID:25500372

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

PubMed Central

Siwy, Justyna; Schanstra, Joost P.; Argiles, Angel; Bakker, Stephan J.L.; Beige, Joachim; Boucek, Petr; Brand, Korbinian; Delles, Christian; Duranton, Flore; Fernandez-Fernandez, Beatriz; Jankowski, Marie-Luise; Al Khatib, Mohammad; Kunt, Thomas; Lajer, Maria; Lichtinghagen, Ralf; Lindhardt, Morten; Maahs, David M; Mischak, Harald; Mullen, William; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Persson, Frederik; Petrie, John R.; Roob, Johannes M.; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Snell-Bergeon, Janet; Spasovski, Goce; Stojceva-Taneva, Olivera; Trillini, Matias; von der Leyen, Heiko; Winklhofer-Roob, Brigitte M.; Zürbig, Petra; Jankowski, Joachim

2014-01-01

Background Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). Methods In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. Results We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16–89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. Conclusion We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial. PMID:24589724

Pressure ulcer knowledge of registered nurses, assistant nurses and student nurses: a descriptive, comparative multicentre study in Sweden.

PubMed

Gunningberg, Lena; Mårtensson, Gunilla; Mamhidir, Anna-Greta; Florin, Jan; Muntlin Athlin, Åsa; Bååth, Carina

2015-08-01

The aim of this study was to describe and compare the knowledge of registered nurses (RNs), assistant nurses (ANs) and student nurses (SNs) about preventing pressure ulcers (PUs). PU prevention behaviours in the clinical practice of RNs and ANs were also explored. A descriptive, comparative multicentre study was performed. Hospital wards and universities from four Swedish county councils participated. In total, 415 participants (RN, AN and SN) completed the Pressure Ulcer Knowledge Assessment Tool. The mean knowledge score for the sample was 58·9%. The highest scores were found in the themes 'nutrition' (83·1%) and 'risk assessment' (75·7%). The lowest scores were found in the themes 'reduction in the amount of pressure and shear' (47·5%) and 'classification and observation' (55·5%). RNs and SNs had higher scores than ANs on 'aetiology and causes'. SNs had higher scores than RNs and ANs on 'nutrition'. It has been concluded that there is a knowledge deficit in PU prevention among nursing staff in Sweden. A major educational campaign needs to be undertaken both in hospital settings and in nursing education. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

The accuracy of colonoscopic localisation of colorectal tumours: a prospective, multi-centred observational study.

PubMed

Johnstone, M S; Moug, S J

2014-05-01

Colonoscopy is essential for accurate pre-operative colorectal tumour localisation, but its accuracy for localisation remains undetermined due to limitations of previous work. This study aimed to establish the accuracy of colonoscopic localisation and to determine how frequently inaccuracy results in altered surgical management. A prospective, multi-centred, powered observational study recruited 79 patients with colorectal tumours that underwent curative surgical resection. Patient and colonoscopic factors were recorded. Pre-operative colonoscopic and radiological lesion localisations were compared to intra-operative localisation using pre-defined anatomical bowel segments to determine accuracy, with changes in planned surgical management documented. Colonoscopy accurately located the colorectal tumour in 64/79 patients (81%). Five out of 15 inaccurately located patients required on-table alteration in planned surgical management. Pre-operative imaging was unable to visualise the primary tumour in 23.1% of cases, a finding that was more prevalent amongst bowel screener patients compared to symptomatic patients (45.8% vs. 13%; p = 0.003). Colonoscopic lesion localisation is inaccurate in 19.0% of cases and occurred throughout the colon with a change in on-table surgical management in 6.3%. With CT unable to visualise lesions in just under a quarter of cases, particularly in the screening population, preoperative localisation is heavily reliant on colonoscopy.

Clinical outcome after the use of a new craniocaudal expandable implant for vertebral compression fracture treatment: one year results from a prospective multicentric study.

PubMed

Noriega, David; Krüger, Antonio; Ardura, Francisco; Hansen-Algenstaedt, Nils; Hassel, Frank; Barreau, Xavier; Beyerlein, Jörg

2015-01-01

The purpose of this prospective multicentric observational study was to confirm the safety and clinical performance of a craniocaudal expandable implant used in combination with high viscosity PMMA bone cement for the treatment of vertebral compression fractures. Thirty-nine VCFs in 32 patients were treated using the SpineJack minimally invasive surgery protocol. Outcome was determined by using the Visual Analogue Scale for measuring pain, the Oswestry Disability Index for scoring functional capacity, and the self-reporting European Quality of Life scores for the quality of life. Safety was evaluated by reporting all adverse events. The occurrence of cement leakages was assessed by either radiographs or CT scan or both. Statistically significant improvements were found regarding pain, function, and quality of life. The global pain score reduction at 1 year was 80.9% compared to the preoperative situation and the result of the Oswestry Disability Index showed a decrease from 65.0% at baseline to 10.5% at 12 months postoperatively. The cement leakage rate was 30.8%. No device- or surgery-related complications were found. This observational study demonstrates promising and persistent results consisting of immediate and sustained pain relief and durable clinical improvement after the procedure and throughout the 1-year follow-up period.

Distribution of causes of maternal mortality during delivery and post-partum: results of an African multicentre hospital-based study.

PubMed

Thonneau, Patrick F; Matsudai, Tomohiro; Alihonou, Eusèbe; De Souza, Jose; Faye, Ousseynou; Moreau, Jean-Charles; Djanhan, Yao; Welffens-Ekra, Christiane; Goyaux, Nathalie

2004-06-15

To assess the maternal mortality ratio in maternity units of reference hospitals in large west African cities, and to describe the distribution of complications and causes of maternal deaths. Prospective descriptive study in twelve reference maternities located in three African countries (Benin, Ivory Coast, Senegal). Data (clinical findings at hospital entry, medical history, complications, type of surgery, vital status of the women at discharge) were collected from obstetrical and surgical files and from admission hospital registers. All cases of maternal deaths were systematically reviewed by African and European staff. Of a total of 10,515 women, 1495 presented a major obstetric complication with dystocia or inappropriate management of the labour phase as the leading cause. Eighty-five maternal deaths were reported, giving a global hospital-based maternal mortality ratio of 800/100,000. Hypertensive disorders were involved in 25/85 cases (29%) and post-partum haemorrhage in 13/85 cases (15%). Relatively few cases (14) of major sepsis were reported, leading to three maternal deaths. The results of this multicentre study confirm the high rates of maternal mortality in maternity units of reference hospitals in large African cities, and in addition to dystocia the contribution of hypertensive disorders and post-partum haemorrhage to maternal deaths.

MRI of the wrist in juvenile idiopathic arthritis: proposal of a paediatric synovitis score by a consensus of an international working group. Results of a multicentre reliability study.

PubMed

Damasio, Maria Beatrice; Malattia, Clara; Tanturri de Horatio, Laura; Mattiuz, Chiara; Pistorio, Angela; Bracaglia, Claudia; Barbuti, Domenico; Boavida, Peter; Juhan, Karen Lambot; Ording, Lil Sophie Mueller; Rosendahl, Karen; Martini, Alberto; Magnano, GianMichele; Tomà, Paolo

2012-09-01

MRI is a sensitive tool for the evaluation of synovitis in juvenile idiopathic arthritis (JIA). The purpose of this study was to introduce a novel MRI-based score for synovitis in children and to examine its inter- and intraobserver variability in a multi-centre study. Wrist MRI was performed in 76 children with JIA. On postcontrast 3-D spoiled gradient-echo and fat-suppressed T2-weighted spin-echo images, joint recesses were scored for the degree of synovial enhancement, effusion and overall inflammation independently by two paediatric radiologists. Total-enhancement and inflammation-synovitis scores were calculated. Interobserver agreement was poor to moderate for enhancement and inflammation in all recesses, except in the radioulnar and radiocarpal joints. Intraobserver agreement was good to excellent. For enhancement and inflammation scores, mean differences (95 % CI) between observers were -1.18 (-4.79 to 2.42) and -2.11 (-6.06 to 1.83). Intraobserver variability (reader 1) was 0 (-1.65 to 1.65) and 0.02 (-1.39 to 1.44). Intraobserver agreement was good. Except for the radioulnar and radiocarpal joints, interobserver agreement was not acceptable. Therefore, the proposed scoring system requires further refinement.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Zarzio®, biosimilar of filgrastim, in prophylaxis of chemotherapy-induced neutropenia in routine practice: a French prospective multicentric study.

PubMed

Nahon, Sophie; Rastkhah, Mansour; Ben Abdelghani, Meher; Soumoudronga, Ravaka-Fatoma; Gasnereau, Isabelle; Labourey, Jean-Luc

2016-05-01

Chemotherapy-induced neutropenia is a serious and potentially life-threatening consequence of cancer treatment. Prophylactic treatment with granulocyte-colony stimulating factor (G-CSF) decreases the incidence of febrile neutropenia, the rate of hospitalization, and the use of antibiotics in patients at risk. The aim of this study was to assess efficacy, safety, and use of Zarzio(®)-biosimilar of Neupogen(®) (G-CSF; filgrastim)-in prophylaxis of chemotherapy-induced neutropenia in current practice in cancer patients. We conducted an observational, prospective, longitudinal, and multicentric study in France. The incidence of neutropenia was evaluated at each cycle of chemotherapy. One hundred eighty-four patients (women, 64.7 %; mean age, 61.7 years) with solid tumor (89.7 %; breast cancer, 50.5 %) or non-Hodgkin lymphoma (10.3 %) were included. The risk of febrile neutropenia based on chemotherapy regimen was >20 % for 32.1 % of patients. No case of febrile neutropenia was reported. Neutropenia was the cause of hospitalization and/or antibiotic therapy in 10 patients. The most frequent adverse events related to Zarzio(®) were pain, in particular bone pain. No serious adverse event related to Zarzio(®) was reported. The results obtained in real-life conditions confirm that Zarzio(®) is efficient and well tolerated in cancer patients.

Receptor for advanced glycation end-products and ARDS prediction: a multicentre observational study.

PubMed

Jabaudon, Matthieu; Berthelin, Pauline; Pranal, Thibaut; Roszyk, Laurence; Godet, Thomas; Faure, Jean-Sébastien; Chabanne, Russell; Eisenmann, Nathanael; Lautrette, Alexandre; Belville, Corinne; Blondonnet, Raiko; Cayot, Sophie; Gillart, Thierry; Pascal, Julien; Skrzypczak, Yvan; Souweine, Bertrand; Blanchon, Loic; Sapin, Vincent; Pereira, Bruno; Constantin, Jean-Michel

2018-02-08

Acute respiratory distress syndrome (ARDS) prediction remains challenging despite available clinical scores. To assess soluble receptor for advanced glycation end-products (sRAGE), a marker of lung epithelial injury, as a predictor of ARDS in a high-risk population, adult patients with at least one ARDS risk factor upon admission to participating intensive care units (ICUs) were enrolled in a multicentre, prospective study between June 2014 and January 2015. Plasma sRAGE and endogenous secretory RAGE (esRAGE) were measured at baseline (ICU admission) and 24 hours later (day one). Four AGER candidate single nucleotide polymorphisms (SNPs) were also assayed because of previous reports of functionality (rs1800625, rs1800624, rs3134940, and rs2070600). The primary outcome was ARDS development within seven days. Of 500 patients enrolled, 464 patients were analysed, and 59 developed ARDS by day seven. Higher baseline and day one plasma sRAGE, but not esRAGE, were independently associated with increased ARDS risk. AGER SNP rs2070600 (Ser/Ser) was associated with increased ARDS risk and higher plasma sRAGE in this cohort, although confirmatory studies are needed to assess the role of AGER SNPs in ARDS prediction. These findings suggest that among at-risk ICU patients, higher plasma sRAGE may identify those who are more likely to develop ARDS.

Epidemiological multicentre study on the education provided to patients with type 2 diabetes mellitus in the Spanish Health Care System. The Forma2 study.

PubMed

García-Donaire, J A; Franch-Nadal, J; Rodríguez-Fortúnez, P; Labrador-Barba, E; Orera-Peña, M L; Rodríguez de Miguel, M

The purpose of the present study was to characterize the education that patients with type 2 diabetes mellitus receive, and to identify differences as regards the presence of insulin therapy or not. This crossover, multicentre and descriptive study involved 1066 Spanish physicians who completed a questionnaire on Internet. The physicians that responded had a mean of 26.0 years of experience in healthcare, and mainly worked in a walk-in clinic in an urban area. Physicians rated the level of patient knowledge about their disease on a 5.0 point-scale. Fifty percent of them indicated that they spent between 15 and 30min in educating patients at the time of diagnosis. Previous control with HbA1c>9%, presence of microvascular complications, and a low socio-cultural level, were factors associated with spending more time in education. This is the first study designed to evaluate the education provided to patients with type 2 diabetes mellitus from Spain. The time spent and the individualization of the education are important factors associated with better long-term control of the disease, and thus with the effectiveness of the clinical management. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

PubMed

Walker, William C; Nowak, Kayla J; Kenney, Kimbra; Franke, Laura Manning; Eapen, Blessen C; Skop, Karen; Levin, Harvey; Agyemang, Amma A; Tate, David F; Wilde, Elisabeth A; Hinds, Sidney; Nolen, Tracy L

2018-06-12

Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. Chronic Effects of Neurotrauma Consortium (CENC) centres. The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. Observational study with cross-sectional analyses using structural equation modelling. Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

CADASIL: Treatment and Management Options.

PubMed

Bersano, Anna; Bedini, Gloria; Oskam, Joshua; Mariotti, Caterina; Taroni, Franco; Baratta, Silvia; Parati, Eugenio Agostino

2017-09-01

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

A UK NEQAS ICC and ISH multicentre study using the Kreatech Poseidon HER2 FISH probe: intersite variation can be rigorously controlled using FISH.

PubMed

Bartlett, John M S; Campbell, Fiona M; Ibrahim, Merdol; Thomas, Jeremy; Wencyk, Pete; Ellis, Ian; Kay, Elaine; Connolly, Yvonne; O'Grady, Anthony; Barnett, Sarah; Starczynski, Jane; Cunningham, Paul; Miller, Keith

2010-02-01

To assess a new HER2 fluorescence in situ hybridization (FISH) test and report on multicentre intrasite and intersite variation. HER2 results were scored from 45 breast cancers in eight laboratories using the Kreatech Poseidon HER2 FISH probe (Kreatech Diagnostics, Amsterdam, the Netherlands). Overall, 80.9% of cores were successfully analysed. Mean intrasite variation for HER2 ratio assessment was low (4.74%). Intersite variation in ratio was in line with previous reports (11.9+/-0.8%) for both reference and non-reference laboratories; only one laboratory displayed significantly higher intersite variation (P=0.009) than the remaining seven laboratories. The overall incidence of misclassification of cores was <1.3%, demonstrating an excellent level of concordance (>98.7%) across all eight laboratories, irrespective of whether they were 'reference' or 'routine diagnostic' laboratories. The Kreatech Poseidon HER2 FISH test is robust and reproducible. Highly quantitatively reproducible FISH results were obtained from eight 'diagnostic' and 'reference' laboratories; however, continued quality assessments are essential to good performance.

MAFB Determines Human Macrophage Anti-Inflammatory Polarization: Relevance for the Pathogenic Mechanisms Operating in Multicentric Carpotarsal Osteolysis.

PubMed

Cuevas, Víctor D; Anta, Laura; Samaniego, Rafael; Orta-Zavalza, Emmanuel; Vladimir de la Rosa, Juan; Baujat, Geneviève; Domínguez-Soto, Ángeles; Sánchez-Mateos, Paloma; Escribese, María M; Castrillo, Antonio; Cormier-Daire, Valérie; Vega, Miguel A; Corbí, Ángel L

2017-03-01

Macrophage phenotypic and functional heterogeneity derives from tissue-specific transcriptional signatures shaped by the local microenvironment. Most studies addressing the molecular basis for macrophage heterogeneity have focused on murine cells, whereas the factors controlling the functional specialization of human macrophages are less known. M-CSF drives the generation of human monocyte-derived macrophages with a potent anti-inflammatory activity upon stimulation. We now report that knockdown of MAFB impairs the acquisition of the anti-inflammatory profile of human macrophages, identify the MAFB-dependent gene signature in human macrophages and illustrate the coexpression of MAFB and MAFB-target genes in CD163 + tissue-resident and tumor-associated macrophages. The contribution of MAFB to the homeostatic/anti-inflammatory macrophage profile is further supported by the skewed polarization of monocyte-derived macrophages from multicentric carpotarsal osteolysis (Online Mendelian Inheritance in Man #166300), a pathology caused by mutations in the MAFB gene. Our results demonstrate that MAFB critically determines the acquisition of the anti-inflammatory transcriptional and functional profiles of human macrophages. Copyright © 2017 by The American Association of Immunologists, Inc.

Maintenance Cognitive Stimulation Therapy (CST) for dementia: A single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia

PubMed Central

2010-01-01

Background Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. Methods/Design This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks. The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. Discussion A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors. Trial Registration ISRCTN26286067 PMID:20426866

Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study.

PubMed

Balasubramaniam, Gowrie; Parker, Trisha; Turner, David; Parker, Mike; Scales, Jonathan; Harnett, Patrick; Harrison, Michael; Ahmed, Khalid; Bhagat, Sweta; Marianayagam, Thiraupathy; Pitzalis, Costantino; Mallen, Christian; Roddy, Edward; Almond, Mike; Dasgupta, Bhaskar

2017-09-05

Acute gout occurs in people with chronic kidney disease, who are commonly older people with comorbidities such as hypertension, heart disease and diabetes. Potentially harmful treatments are administered to these vulnerable patients due to a lack of clear evidence. Newly available treatment that targets a key inflammatory pathway in acute gout attacks provides an opportunity to undertake the first-ever trial specifically looking treating people with kidney disease. This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. The primary objective is to assess the feasibility of the trial design and procedures for a definitive RCT. The specific aims are: (1) test recruitment and retention rates and willingness to be randomised; (2) test eligibility criteria; (3) collect and analyse outcome data to inform sample and power calculations for a trial of efficacy; (4) collect economic data to inform a future economic evaluation estimating costs of treatment and (5) assess capacity of the project to scale up to a national multicentre trial. We will also gather qualitative insights from participants. It aims to recruit 32 patients with a 1:1 randomisation. Information from this feasibility study will help design a definitive trial and provide general information in designing acute gout studies. The London-Central Ethics Committee approved the protocol. The results will be disseminated in peer-reviewed journals and at scientific conferences. EudraCT No. 2015-001787-19, NCT/Clinicalstrials.gov No. NCT02578394, pre-results, WHO Universal Trials Reference No. U1111-1175-1977. NIHR Grant PB-PG-0614-34090. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study

PubMed Central

Snowdon, Claire; Elbourne, Diana R; Garcia, Jo; Campbell, Marion K; Entwistle, Vikki A; Francis, David; Grant, Adrian M; Knight, Rosemary C; McDonald, Alison M; Roberts, Ian

2006-01-01

Background Securing and managing finances for multicentre randomised controlled trials is a highly complex activity which is rarely considered in the research literature. This paper describes the process of financial negotiation and the impact of financial considerations in four UK multicentre trials. These trials had met, or were on schedule to meet, recruitment targets agreed with their public-sector funders. The trials were considered within a larger study examining factors which might be associated with trial recruitment (STEPS). Methods In-depth semi-structured telephone interviews were conducted in 2003–04 with 45 individuals with various responsibilities to one of the four trials. Interviewees were recruited through purposive and then snowball sampling. Interview transcripts were analysed with the assistance of the qualitative package Atlas-ti. Results The data suggest that the UK system of dividing funds into research, treatment and NHS support costs brought the trial teams into complicated negotiations with multiple funders. The divisions were somewhat malleable and the funding system was used differently in each trial. The fact that all funders had the potential to influence and shape the trials considered here was an important issue as the perspectives of applicants and funders could diverge. The extent and range of industry involvement in non-industry-led trials was striking. Three broad periods of financial work (foundation, maintenance, and resourcing completion) were identified. From development to completion of a trial, the trialists had to be resourceful and flexible, adapting to changing internal and external circumstances. In each period, trialists and collaborators could face changing costs and challenges. Each trial extended the recruitment period; three required funding extensions from MRC or HTA. Conclusion This study highlights complex financial aspects of planning and conducting trials, especially where multiple funders are involved. Recognition of the importance of financial stability and of the need for appropriate training in this area should be paralleled by further similar research with a broader range of trials, aimed at understanding and facilitating the conduct of clinical research. PMID:17184521

Maintenance Cognitive Stimulation Therapy (CST) for dementia: a single-blind, multi-centre, randomized controlled trial of Maintenance CST vs. CST for dementia.

PubMed

Aguirre, Elisa; Spector, Aimee; Hoe, Juanita; Russell, Ian T; Knapp, Martin; Woods, Robert T; Orrell, Martin

2010-04-28

Psychological treatments for dementia are widely used in the UK and internationally, but only rarely have they been standardised, adequately evaluated or systematically implemented. There is increasing recognition that psychosocial interventions may have similar levels of effectiveness to medication, and both can be used in combination. Cognitive Stimulation Therapy (CST) is a 7-week cognitive-based approach for dementia that has been shown to be beneficial for cognition and quality of life and is cost-effective, but there is less conclusive evidence for the effects of CST over an extended period. This multi-centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of Maintenance CST groups for dementia compares a intervention group who receive CST for 7 weeks followed by the Maintenance CST programme once a week for 24 weeks with the control group who receive CST for 7 weeks, followed by treatment as usual for 24 weeks.The primary outcome measures are quality of life of people with dementia assessed by the QoL-AD and cognition assessed by the ADAS-Cog. Secondary outcomes include the person with dementia's mood, behaviour, activities of daily living, ability to communicate and costs; as well as caregiver health-related quality of life. Using a 5% significance level, comparison of 230 participants will yield 80% power to detect a standardised difference of 0.39 on the ADAS-Cog between the groups. The trial includes a cost-effectiveness analysis from a public sector perspective. A pilot study of longer-term Maintenance CST, offering 16 weekly sessions of maintenance following the initial CST programme, previously found a significant improvement in cognitive function (MMSE) for those on the intervention group. The study identified the need for a large-scale, multi-centre RCT to define the potential longer-term benefits of continuing the therapy. This study aims to provide definitive evidence of the potential efficacy of maintenance CST and establish how far the long-term benefits can be compared with antidementia drugs such as cholinesterase inhibitors.

Ankle Injury Management (AIM): design of a pragmatic multi-centre equivalence randomised controlled trial comparing Close Contact Casting (CCC) to Open surgical Reduction and Internal Fixation (ORIF) in the treatment of unstable ankle fractures in patients over 60 years.

PubMed

Willett, Keith; Keene, David J; Morgan, Lesley; Gray, Bridget; Handley, Robert; Chesser, Tim; Pallister, Ian; Tutton, Elizabeth; Knox, Christopher; Lall, Ranjit; Briggs, Andrew; Lamb, Sarah E

2014-03-12

Ankle fractures account for 9% of all fractures with a quarter of these occurring in adults over 60 years. The short term disability and long-term consequences of this injury can be considerable. Current opinion favours open reduction and internal fixation (ORIF) over non-operative treatment (fracture manipulation and the application of a standard moulded cast) for older people. Both techniques are associated with complications but the limited published research indicates higher complication rates of fracture malunion (poor position at healing) with casting. The aim of this study is to compare ORIF with a modification of existing casting techniques, Close Contact Casting (CCC). We propose that CCC may offer an equivalent functional outcome to ORIF and avoid the risks associated with surgery. This study is a pragmatic multi-centre equivalence randomised controlled trial. 620 participants will be randomised to receive ORIF or CCC after sustaining an isolated displaced unstable ankle fracture. Participants will be recruited from a minimum of 20 National Health Service (NHS) acute hospitals throughout England and Wales. Participants will be aged over 60 years and be ambulatory prior to injury. Follow-up will be at six weeks and six months after randomisation. The primary outcome is the Olerud & Molander Ankle Score, a functional patient reported outcome measure, at 6 months. Follow-up will also include assessments of mobility, ankle range of movement, health related quality of life and complications. The six-month follow-up will be conducted face-to-face by an assessor blinded to the allocated intervention. A parallel economic evaluation will consider both a health service and a broader societal perspective including the individual and their family. In order to explore patient experience of their treatment and recovery, a purposive sample of 40 patients will also be interviewed using a semi-structured interview schedule between 6-10 weeks post treatment. This multicentre study was open to recruitment July 2010 and recruitment is due to be completed in December 2013. Current Controlled Trials ISRCTN04180738.

The role of dosimetry audit in lung SBRT multi-centre clinical trials.

PubMed

Clark, Catharine H; Hurkmans, Coen W; Kry, Stephen F

2017-12-01

Stereotactic Body Radiotherapy (SBRT) in the lung is a challenging technique which requires high quality clinical trials to answer the un-resolved clinical questions. Quality assurance of these clinical trials not only ensures the safety of the treatment of the participating patients but also minimises the variation in treatment, thus allowing the lowest number of patient treatments to answer the trial question. This review addresses the role of dosimetry audits in the quality assurance process and considers what can be done to ensure the highest accuracy of dose calculation and delivery and it's assessment in multi-centre trials. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease.

PubMed

Matsuyama, Masashi; Suzuki, Takeshi; Tsuboi, Hiroto; Ito, Satoshi; Mamura, Mizuko; Goto, Daisuke; Matsumoto, Isao; Tsutsumi, Akito; Sumida, Takayuki

2007-01-01

We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.

Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

PubMed

van der Kooi, Tjallie; Sax, Hugo; Pittet, Didier; van Dissel, Jaap; van Benthem, Birgit; Walder, Bernhard; Cartier, Vanessa; Clack, Lauren; de Greeff, Sabine; Wolkewitz, Martin; Hieke, Stefanie; Boshuizen, Hendriek; van de Kassteele, Jan; Van den Abeele, Annemie; Boo, Teck Wee; Diab-Elschahawi, Magda; Dumpis, Uga; Ghita, Camelia; FitzGerald, Susan; Lejko, Tatjana; Leleu, Kris; Martinez, Mercedes Palomar; Paniara, Olga; Patyi, Márta; Schab, Paweł; Raglio, Annibale; Szilágyi, Emese; Ziętkiewicz, Mirosław; Wu, Albert W; Grundmann, Hajo; Zingg, Walter

2018-01-01

To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

Crisaborole Ointment 2%: A Review in Mild to Moderate Atopic Dermatitis.

PubMed

Hoy, Sheridan M

2017-12-01

Crisaborole ointment 2% (Eucrisa™) is a novel, anti-inflammatory inhibitor of phosphodiesterase 4 (PDE4) that is available in the USA for the topical treatment of mild to moderate atopic dermatitis in patients aged ≥ 2 years. In two short-term (28 days), identically designed, multicentre, phase III studies in this patient population, topical therapy with crisaborole ointment 2% reduced disease severity and pruritus severity compared with vehicle, with the effect established early and sustained over the course of treatment. Improvements in the other signs of atopic dermatitis (erythema, exudation, excoriation, induration/papulation, and lichenification) were also seen. Crisaborole ointment 2% was generally well tolerated in the short-term studies, with its favorable safety profile maintained over the longer term (up to 52 weeks) in a multicentre, extension study. Most treatment-emergent adverse events (TEAEs) were of mild to moderate severity and considered unrelated to the study medication. Moreover, the incidence of application-site pain following short- and longer-term topical therapy with crisaborole ointment 2% was low. In conclusion, crisaborole ointment 2% is an effective and generally well tolerated new topical option for the management of mild to moderate atopic dermatitis in patients aged ≥ 2 years, with the potential to effectively treat this patient population over the longer term without the safety concerns associated with other current topical anti-inflammatory agents.

The Plasma-Lyte 148 v Saline (PLUS) study protocol: a multicentre, randomised controlled trial of the effect of intensive care fluid therapy on mortality.

PubMed

Hammond, Naomi E; Bellomo, Rinaldo; Gallagher, Martin; Gattas, David; Glass, Parisa; Mackle, Diane; Micallef, Sharon; Myburgh, John; Saxena, Manoj; Taylor, Colman; Young, Paul; Finfer, Simon

2017-09-01

0.9% sodium chloride (saline) is the most commonly administered resuscitation fluid on a global basis but emerging evidence suggests that its high chloride content may have important adverse effects. To describe the study protocol for the Plasma- Lyte 148 v Saline study, which will test the hypothesis that in critically ill adult patients the use of Plasma-Lyte 148 (a buffered crystalloid solution) for fluid therapy results in different 90-day all-cause mortality when compared with saline. We will conduct this multicentre, blinded, randomised controlled trial in approximately 50 intensive care units in Australia and New Zealand. We will randomly assign 8800 patients to either Plasma-Lyte 148 or saline for all resuscitation fluid, maintenance fluid and compatible drug dilution therapy while in the ICU for up to 90 days after randomisation. The primary outcome is 90-day all-cause mortality; secondary outcomes include mean and peak creatinine concentration, incidence of renal replacement therapy, incidence and duration of vasoactive drug treatment, duration of mechanical ventilation, ICU and hospital length of stay, and quality of life and health services use at 6 months. The PLUS study will provide high-quality data on the comparative safety and efficacy of Plasma-Lyte 148 compared with saline for resuscitation and compatible crystalloid fluid therapy in critically ill adult patients.

Coping strategies for postpartum depression: a multi-centric study of 1626 women.

PubMed

Gutiérrez-Zotes, Alfonso; Labad, Javier; Martín-Santos, Rocío; García-Esteve, Luisa; Gelabert, Estel; Jover, Manuel; Guillamat, Roser; Mayoral, Fermín; Gornemann, Isolde; Canellas, Francesca; Gratacós, Mónica; Guitart, Montserrat; Roca, Miguel; Costas, Javier; Ivorra, Jose Luis; Navinés, Ricard; de Diego-Otero, Yolanda; Vilella, Elisabet; Sanjuan, Julio

2016-06-01

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Multicentre study of fragrance allergy in Hungary. Immediate and late type reactions.

PubMed

Temesvári, Erzsébet; Németh, Ilona; Baló-Banga, Mátyás J; Husz, Sándor; Kohánka, Valéria; Somos, Zsuzsa; Judák, Rita; Remenyik, E V A; Szegedi, Andrea; Nebenführer, László; Mészáros, Csilla; Horváth, Attila

2002-06-01

The authors followed the frequency of fragrance contact sensitization in Hungary in a multicentre study in the years 1998 and 1999. A total of 3,604 patients were tested with fragrance mix (FM), and positive reactions were observed in 294 (8.2%). In 160 FM hypersensitive patients, the study was continued with patch testing of the mix constituents (cinnamic alcohol, cinnamic aldehyde, eugenol, amyl cinnamic aldehyde, hydroxycitronellal, geraniol, isoeugenol, oak moss absolute). Of the patients tested, 70.6% produced positive reactions to the constituents. FM contact sensitization was mainly observed in female patients (74.4%). The incidence of contact urticaria in FM hypersensitive patients was 6.1%. Simultaneous patch test trials of other environmental contact allergens, in both early and late evaluations, mainly confirmed hypersensitivity reactions to balsams. Female dominance of hypersensitivity reactions observed during testing the individual components of the mix was striking (82.4%). In positive skin reactions, cinnamic alcohol, isoeugenol and oak moss provoked skin symptoms most frequently. We also tested the 104 patients who produced negative reactions to FM with the constituent individual allergens, with 11.9% positive incidence. The clinical symptoms of the patients were above all manifest in the form of contact eczema, located on the hands, face, eyelids and axillae. With this study, the authors, members of the Hungarian Contact Dermatitis Research Group, call attention to one of the most frequent allergens in the environment.

Using straw hydrolysate to cultivate Chlorella pyrenoidosa for high-value biomass production and the nitrogen regulation for biomass composition.

PubMed

Zhang, Tian-Yuan; Wang, Xiao-Xiong; Wu, Yin-Hu; Wang, Jing-Han; Deantes-Espinosa, Victor M; Zhuang, Lin-Lan; Hu, Hong-Ying; Wu, Guang-Xue

2017-11-01

Heterotrophic cultivation of Chlorella pyrenoidosa based on straw substrate was proposed as a promising approach in this research. The straw pre-treated by ammonium sulfite method was enzymatically hydrolyzed for medium preparation. The highest intrinsic growth rate of C. pyrenoidosa reached to 0.097h -1 in hydrolysate medium, which was quicker than that in glucose medium. Rising nitrogen concentration could significantly increase protein content and decrease lipid content in biomass, meanwhile fatty acids composition kept stable. The highest protein and lipid content in microalgal biomass reached to 62% and 32% under nitrogen excessive and deficient conditions, respectively. Over 40% of amino acids and fatty acids in biomass belonged to essential amino acids (EAA) and essential fatty acids (EFA), which were qualified for high-value uses. This research revealed the rapid biomass accumulation property of C. pyrenoidosa in straw hydrolysate medium and the effectiveness of nitrogen regulation to biomass composition at heterotrophic condition. Copyright © 2017. Published by Elsevier Ltd.

Branched Chain Amino Acids: Beyond Nutrition Metabolism.

PubMed

Nie, Cunxi; He, Ting; Zhang, Wenju; Zhang, Guolong; Ma, Xi

2018-03-23

Branched chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), play critical roles in the regulation of energy homeostasis, nutrition metabolism, gut health, immunity and disease in humans and animals. As the most abundant of essential amino acids (EAAs), BCAAs are not only the substrates for synthesis of nitrogenous compounds, they also serve as signaling molecules regulating metabolism of glucose, lipid, and protein synthesis, intestinal health, and immunity via special signaling network, especially phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signal pathway. Current evidence supports BCAAs and their derivatives as the potential biomarkers of diseases such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), cancer, and cardiovascular diseases (CVDs). These diseases are closely associated with catabolism and balance of BCAAs. Hence, optimizing dietary BCAA levels should have a positive effect on the parameters associated with health and diseases. This review focuses on recent findings of BCAAs in metabolic pathways and regulation, and underlying the relationship of BCAAs to related disease processes.

Food intake and the risk of endometrial endometrioid adenocarcinoma in Japanese women.

PubMed

Takayama, Shin; Monma, Yasutake; Tsubota-Utsugi, Megumi; Nagase, Satoru; Tsubono, Yoshitaka; Numata, Takehiro; Toyoshima, Masafumi; Utsunomiya, Hiroki; Sugawara, Junichi; Yaegashi, Nobuo

2013-01-01

The present study examined the association between food intake and endometrial cancer restricted to endometrial endometrioid adenocarcinoma (EEA) using a case-control study in Japanese women. One hundred sixty-one cases and 380 controls who completed a questionnaire regarding demographic, lifestyle, and food frequency questionnaire were analyzed. Odds ratio (OR) between selected food intakes and EEA were calculated by logistic regression analysis. After adjustment putative confounding factors, the higher intakes of vegetables [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.26-0.83], peanuts (OR = 0.48, CI = 0.27-0.86), fish (OR = 0.52, CI = 0.29-0.93), boiled egg (OR = 0.24, CI = 0.33-0.92), instant noodles (OR = 1.94, CI = 1.12-3.34), instant food items (OR = 2.21, CI = 1.31-3.74), and deep-fried foods (OR = 2.87, CI = 1.58-5.21) were associated with a risk for EEA. The inverse association with a risk of EEA was also seen in higher intakes (g/1000 kcal) for vegetables (0.45, CI = 0.25-0.81) and fish (0.53, CI = 0.30-0.94) as compare to lower intake. Higher intake of vegetables, peanuts, fish, and boiled egg was associated with a reduced risk for EEA, whereas instant noodles, instant food items, and deep-fried foods was associated with an increased risk for EAA as compared to lower levels of intake.

A multicentre 'end to end' dosimetry audit for cervix HDR brachytherapy treatment.

PubMed

Palmer, Antony L; Diez, Patricia; Gandon, Laura; Wynn-Jones, Andrea; Bownes, Peter; Lee, Chris; Aird, Edwin; Bidmead, Margaret; Lowe, Gerry; Bradley, David; Nisbet, Andrew

2015-02-01

To undertake the first multicentre fully 'end to end' dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. The mean difference between planned and measured dose at Point A was -0.6% for plastic applicators and -3.0% for metal applicators, at standard uncertainty 3.0% (k=1). Isodose distributions agreed within 1mm over a dose range 2-16Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. The concept of 'end to end' dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmaceutical trials in general practice: the first 100 protocols. An audit by the clinical research ethics committee of the Royal College of General Practitioners.

PubMed Central

Wise, P.; Drury, M.

1996-01-01

OBJECTIVE: To assess the outcome of 100 general practice based, multicentre research projects submitted to the ethics committee of the Royal College of General Practitioners by pharmaceutical companies or their agents between 1984 and 1989. DESIGN: Analysis of consecutive submitted protocols for stated objectives, study design, and outcomes; detailed review of committee minutes and correspondence in relation to amendment and approval; assessment of final reports submitted at conclusion of studies. SUBJECTS: 82 finally approved protocols, embracing 34,523 proposed trial subjects and 1195 proposed general practice investigators. MAIN OUTCOME MEASURES: Success at enrolling subjects and investigators; commencement and completion data; validity of final report's assessment of efficacy, safety, tolerability, and acceptability; and method of use and dissemination of findings. RESULTS: 18 studies were not approved and 45 had to be amended. Randomised controlled trials comprised 46 of the original submissions. Remuneration considerations, inadequate information or consent sheets, pregnancy safety, the need to discontinue existing therapy, and suboptimal scientific content were major reasons for rejecting studies or asking for amendments. Of the 82 approved studies 8 were not started. Shortfalls of investigators (of 39%) and trial subjects (of 37%) and an overall 23% withdrawal rate were responsible for a significant incidence of inconclusive results. Within the six year follow up interval, only 19 of the studies had been formally published. CONCLUSIONS: This audit identified substantial ethical concerns in the process of approving multicentre general practice pharmaceutical research. PMID:8939118

Utility of Von Pechman synthesis of coumarin reaction for development of spectrofluorimetric method for quantitation of salmeterol xinafoate in pharmaceutical preparations and human plasma.

PubMed

Awad, Mohamed; Hammad, Mohamed A; Abdel-Megied, Ahmed M; Omar, Mahmoud A

2018-04-30

Simple, precise and selective spectrofluorimetric technique was evolved for quantitation of selective β 2 agonist drug namely salmeterol xinafoate (SAL). Utilizing its phenolic nature, a method was described based on the reaction of the studied drug with ethyl acetoacetate (EAA) to yield extremely fluorescent coumarin product which can be detected at 480 nm (λ ex  = 420 nm). The procedure obeys Beer's law with a correlation coefficient of r = 0.9999 in the concentration range between 500 and 5000 ng ml -1 with and 177 ng ml -1 for limit of detection (LOD) and limit of quantification (LOQ), respectively. Diverse reaction variables influencing the firmness and formation of the coumarin product were accurately examined and modified to ensure greatest sensitivity of the procedure. The proposed technique was performed and examined according to the US Food and Drug Administration (FDA) guidelines for bio-analytical methods and was efficiently applied for quantitation of SAL in both pharmaceutical preparations (% recovery = 100.06 ± 1.07) and spiked human plasma (% recovery = 96.64-97.14 ± 1.01-1.52). Copyright © 2018 John Wiley & Sons, Ltd.

Decrement in operant performance produced by NMDA receptor antagonists in the rat: tolerance and cross-tolerance.

PubMed

Dravolina, O A; Zvartau, E E; Bespalov, A Y

2000-04-01

Current perspectives on the clinical use of NMDA receptor antagonists infer repeated administration schedules for the management of different pathological states. The development of tolerance and cross-tolerance between different NMDA receptor antagonists may be an important factor contributing to the clinical efficacy of these drugs. The present study aimed to characterize the development of tolerance and cross-tolerance to the ability of various site-selective NMDA receptor antagonists to produce a decrement of operant responding (multiple extinction 9 s fixed-interval 1-s schedule of water reinforcement). Acute administration of D-CPPen (SDZ EAA 494; 1-5.6 mg/kg), dizocilpine (MK-801; 0.03-0.3 mg/kg), memantine (0.3-17 mg/kg), ACEA-1021 (10-56 mg/kg), and eliprodil (1-30 mg/kg) differentially affected operant responding. Both increases and decreases in response rates and accuracy of responding were observed. Repeated preexposure to D-CPPen (5.6 mg/kg, once a day for 7 days) attenuated a behavioral disruption produced by an acute challenge with D-CPPen or ACEA-1021, but potentiated the effects of dizocilpine, memantine, and eliprodil. Based on the present results, one can suggest that the repeated administration of a competitive NMDA receptor antagonist differentially affects the functional activity of various sites on NMDA receptor complex.

Serological markers of hepatitis B in patients with alcoholic liver disease: a multi-centre survey

PubMed Central

Hislop, WS; Follett, EAC; Bouchier, IAD; MacSween, RNM

1981-01-01

In a study of 195 patients derived from five centres in northern Britain and with histologically confirmed alcoholic liver disease we have found an increased prevalence of serological markers of hepatitis B. This increased prevalence was found in each of the five centres; the overall frequency ranged from 11% sero-positivity in fatty liver, 12% in alcoholic hepatitis and 27% in cirrhosis. PMID:7276216

En route to Background Independence: Broken split-symmetry, and how to restore it with bi-metric average actions

NASA Astrophysics Data System (ADS)

Becker, D.; Reuter, M.

2014-11-01

The most momentous requirement a quantum theory of gravity must satisfy is Background Independence, necessitating in particular an ab initio derivation of the arena all non-gravitational physics takes place in, namely spacetime. Using the background field technique, this requirement translates into the condition of an unbroken split-symmetry connecting the (quantized) metric fluctuations to the (classical) background metric. If the regularization scheme used violates split-symmetry during the quantization process it is mandatory to restore it in the end at the level of observable physics. In this paper we present a detailed investigation of split-symmetry breaking and restoration within the Effective Average Action (EAA) approach to Quantum Einstein Gravity (QEG) with a special emphasis on the Asymptotic Safety conjecture. In particular we demonstrate for the first time in a non-trivial setting that the two key requirements of Background Independence and Asymptotic Safety can be satisfied simultaneously. Carefully disentangling fluctuation and background fields, we employ a 'bi-metric' ansatz for the EAA and project the flow generated by its functional renormalization group equation on a truncated theory space spanned by two separate Einstein-Hilbert actions for the dynamical and the background metric, respectively. A new powerful method is used to derive the corresponding renormalization group (RG) equations for the Newton- and cosmological constant, both in the dynamical and the background sector. We classify and analyze their solutions in detail, determine their fixed point structure, and identify an attractor mechanism which turns out instrumental in the split-symmetry restoration. We show that there exists a subset of RG trajectories which are both asymptotically safe and split-symmetry restoring: In the ultraviolet they emanate from a non-Gaussian fixed point, and in the infrared they loose all symmetry violating contributions inflicted on them by the non-invariant functional RG equation. As an application, we compute the scale dependent spectral dimension which governs the fractal properties of the effective QEG spacetimes at the bi-metric level. Earlier tests of the Asymptotic Safety conjecture almost exclusively employed 'single-metric truncations' which are blind towards the difference between quantum and background fields. We explore in detail under which conditions they can be reliable, and we discuss how the single-metric based picture of Asymptotic Safety needs to be revised in the light of the new results. We shall conclude that the next generation of truncations for quantitatively precise predictions (of critical exponents, for instance) is bound to be of the bi-metric type.

A scoring system to predict breast cancer mortality at 5 and 10 years.

PubMed

Paredes-Aracil, Esther; Palazón-Bru, Antonio; Folgado-de la Rosa, David Manuel; Ots-Gutiérrez, José Ramón; Compañ-Rosique, Antonio Fernando; Gil-Guillén, Vicente Francisco

2017-03-24

Although predictive models exist for mortality in breast cancer (BC) (generally all cause-mortality), they are not applicable to all patients and their statistical methodology is not the most powerful to develop a predictive model. Consequently, we developed a predictive model specific for BC mortality at 5 and 10 years resolving the above issues. This cohort study included 287 patients diagnosed with BC in a Spanish region in 2003-2016. time-to-BC death. Secondary variables: age, personal history of breast surgery, personal history of any cancer/BC, premenopause, postmenopause, grade, estrogen receptor, progesterone receptor, c-erbB2, TNM stage, multicentricity/multifocality, diagnosis and treatment. A points system was constructed to predict BC mortality at 5 and 10 years. The model was internally validated by bootstrapping. The points system was integrated into a mobile application for Android. Mean follow-up was 8.6 ± 3.5 years and 55 patients died of BC. The points system included age, personal history of BC, grade, TNM stage and multicentricity. Validation was satisfactory, in both discrimination and calibration. In conclusion, we constructed and internally validated a scoring system for predicting BC mortality at 5 and 10 years. External validation studies are needed for its use in other geographical areas.

Direct identification of microorganisms from positive blood cultures using the lysis-filtration technique and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS): a multicentre study.

PubMed

Farina, Claudio; Arena, Fabio; Casprini, Patrizia; Cichero, Paola; Clementi, Massimo; Cosentino, Marina; Degl'Innocenti, Roberto; Giani, Tommaso; Luzzaro, Francesco; Mattei, Romano; Mauri, Carola; Nardone, Maria; Rossolini, Gian Maria; Serna Ortega, Paula Andrea; Vailati, Francesca

2015-04-01

Microbial identification from blood cultures is essential to institute optimal antibiotic therapy and improve survival possibilities. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify bacteria and yeasts from positive blood cultures broths. The aim of this multicentre study was to evaluate the reliability of the lysis-filtration technique associated with MALDI-TOF MS to directly identify microorganisms from 765 positive blood cultures collected in six Italian hospitals. Overall, 675/765 (78.1%) blood isolates were correctly identified at the species level, with significant differences between Gram-negative and Gram-positive bacteria (92.6%, and 69.8%, respectively). Some difficulties arise in identifying Streptococcus pneumoniae, Staphylococcus aureus, yeasts and anaerobes. The lysis-filtration protocol is a suitable procedure in terms of performance in identifying microorganisms, but it is quite expensive and technically time-consuming since the time of filtration is not regular for all the samples. The application of the MALDI-TOF MS technique to the direct microbial identification from positive blood cultures is a very promising approach, even if more experience must be gained to minimize errors and costs.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

PubMed

Kaku, K; Katou, M; Igeta, M; Ohira, T; Sano, H

2015-12-01

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings. © 2015 John Wiley & Sons Ltd.

Decompressive craniectomy and CSF disorders in children.

PubMed

Manfiotto, Marie; Mottolese, Carmine; Szathmari, Alexandru; Beuriat, Pierre-Aurelien; Klein, Olivier; Vinchon, Matthieu; Gimbert, Edouard; Roujeau, Thomas; Scavarda, Didier; Zerah, Michel; Di Rocco, Federico

2017-10-01

Decompressive craniectomy (DC) is a lifesaving procedure but is associated to several post-operative complications, namely cerebrospinal fluid (CSF) dynamics impairment. The aim of this multicentric study was to evaluate the incidence of such CSF alterations after DC and review their impact on the overall outcome. We performed a retrospective multicentric study to analyze the CSF disorders occurring in children aged from 0 to 17 years who had undergone a DC for traumatic brain injury (TBI) in the major Departments of Pediatric Neurosurgery of France between January 2006 and August 2016. Out of 150 children, ranging in age between 7 months and 17 years, mean 10.75 years, who underwent a DC for TBI in 10 French pediatric neurosurgical centers. Sixteen (6 males, 10 females) (10.67%) developed CSF disorders following the surgical procedure and required an extrathecal CSF shunting. External ventricular drainage increased the risk of further complications, especially cranioplasty infection (p = 0.008). CSF disorders affect a minority of children after DC for TBI. They may develop early after the DC but they may develop several months after the cranioplasty (8 months), consequently indicating the necessity of clinical and radiological close follow-up after discharge from the neurosurgical unit. External ventricular drainage and permanent CSF shunt placement increase significantly the risk of cranioplasty infection.

HPV and cofactors for invasive cervical cancer in Morocco: a multicentre case-control study.

PubMed

Berraho, Mohamed; Amarti-Riffi, Afaf; El-Mzibri, Mohammed; Bezad, Rachid; Benjaafar, Noureddine; Benideer, Abdelatif; Matar, Noureddine; Qmichou, Zinab; Abda, Naima; Attaleb, Mohammed; Znati, Kaoutar; El Fatemi, Hind; Bendahhou, Karima; Obtel, Majdouline; Filali Adib, Abdelhai; Mathoulin-Pelissier, Simone; Nejjari, Chakib

2017-06-20

Limited national information is available in Morocco on the prevalence and distribution of HPV-sub-types of cervical cancer and the role of other risk factors. The aim was to determine the frequency of HPV-sub-types of cervical cancer in Morocco and investigate risk factors for this disease. Between November 2009 and April 2012 a multicentre case-control study was carried out. A total of 144 cases of cervical cancer and 288 age-matched controls were included. Odds-ratios and corresponding confidence-intervals were computed by conditional logistic regression models. Current HPV infection was detected in 92.5% of cases and 13.9% of controls. HPV16 was the most common type for both cases and controls. Very strong associations between HPV-sub-types and cervical cancer were observed: total-HPV (OR = 39), HPV16 (OR = 49), HPV18 (OR = 31), and multiple infections (OR = 13). Education, high parity, sexual intercourse during menstruation, history of sexually transmitted infections, and husband's multiple sexual partners were also significantly associated with cervical cancer in the multivariate analysis. Our results could be used to establish a primary prevention program and to prioritize limited screening to women who have specific characteristics that may put them at an increased risk of cervical cancer.

Is breast conservative surgery a reasonable option in multifocal or multicentric tumors?

PubMed Central

Houvenaeghel, Gilles; Tallet, Agnès; Jalaguier-Coudray, Aurélie; Cohen, Monique; Bannier, Marie; Jauffret-Fara, Camille; Lambaudie, Eric

2016-01-01

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A meta-analysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists. PMID:27081646

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

PubMed

Dagostino, Concetta; De Gregori, Manuela; Gieger, Christian; Manz, Judith; Gudelj, Ivan; Lauc, Gordan; Divizia, Laura; Wang, Wei; Sim, Moira; Pemberton, Iain K; MacDougall, Jane; Williams, Frances; Van Zundert, Jan; Primorac, Dragan; Aulchenko, Yurii; Kapural, Leonardo; Allegri, Massimo

2017-01-01

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

Safeguarding the Future of Urological Research and Delivery of Clinical Excellence by Harnessing the Power of Youth to Spearhead Urological Research.

PubMed

Kasivisvanathan, Veeru; Kutikov, Alexander; Manning, Todd G; McGrath, John; Resnick, Matthew J; Sedelaar, J P Michiel; Silay, Mesrur S

2018-05-01

Trainee-led collaboratives offer exciting new perspectives and approaches to urological research. They provide a central network of expertise in methodology, mentoring, and knowledge of research processes that allows the conduct of large multicentre studies that can recruit quickly. This provides the consultant workforce of tomorrow with the skills required to deliver practice-changing clinical studies in urology. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

DISCRIMINATION OF EMOTIONAL STATES AMONGST THE TAMILS

PubMed Central

Somasundaram, O.

1992-01-01

Leff has concluded from his analysis of the JPSS Study that the emotions of anxiety, depression and irritability are poorly discriminated amongst the population using non-Indo-European languages. The present author after analyzing similar data from the ICMR Multicentred Collaborative Study of Factors Associated with the Course and outcome of Schizophrenia that the Tamil population using Tamil, a non-Indo-European language is able to discriminate these emotions as well as the brethren speaking Hindi of lndo-European origin. PMID:21776093

The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies.

PubMed

Löfdahl, C G; Postma, D S; Laitinen, L A; Ohlsson, S V; Pauwels, R A; Pride, N B

1998-03-01

The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.

BreathDx - molecular analysis of exhaled breath as a diagnostic test for ventilator-associated pneumonia: protocol for a European multicentre observational study.

PubMed

van Oort, Pouline M P; Nijsen, Tamara; Weda, Hans; Knobel, Hugo; Dark, Paul; Felton, Timothy; Rattray, Nicholas J W; Lawal, Oluwasola; Ahmed, Waqar; Portsmouth, Craig; Sterk, Peter J; Schultz, Marcus J; Zakharkina, Tetyana; Artigas, Antonio; Povoa, Pedro; Martin-Loeches, Ignacio; Fowler, Stephen J; Bos, Lieuwe D J

2017-01-03

The diagnosis of ventilator-associated pneumonia (VAP) remains time-consuming and costly, the clinical tools lack specificity and a bedside test to exclude infection in suspected patients is unavailable. Breath contains hundreds to thousands of volatile organic compounds (VOCs) that result from host and microbial metabolism as well as the environment. The present study aims to use breath VOC analysis to develop a model that can discriminate between patients who have positive cultures and who have negative cultures with a high sensitivity. The Molecular Analysis of Exhaled Breath as Diagnostic Test for Ventilator-Associated Pneumonia (BreathDx) study is a multicentre observational study. Breath and bronchial lavage samples will be collected from 100 and 53 intubated and ventilated patients suspected of VAP. Breath will be analysed using Thermal Desorption - Gas Chromatography - Mass Spectrometry (TD-GC-MS). The primary endpoint is the accuracy of cross-validated prediction for positive respiratory cultures in patients that are suspected of VAP, with a sensitivity of at least 99% (high negative predictive value). To our knowledge, BreathDx is the first study powered to investigate whether molecular analysis of breath can be used to classify suspected VAP patients with and without positive microbiological cultures with 99% sensitivity. UKCRN ID number 19086, registered May 2015; as well as registration at www.trialregister.nl under the acronym 'BreathDx' with trial ID number NTR 6114 (retrospectively registered on 28 October 2016).

The MOAHLFA index of irritant sodium lauryl sulfate reactions: first results of a multicentre study on routine sodium lauryl sulfate patch testing.

PubMed

Uter, Wolfgang; Geier, Johannes; Becker, Detlef; Brasch, Jochen; Löffler, Harald

2004-01-01

In a multicentre study of the German Contact Dermatitis Research Group, sodium lauryl sulfate (SLS) 0.25% and 0.5% aq. has been added to routine allergen patch tests to assess its properties as a convenient diagnostic indicator of individual susceptibility to irritation at the time of patch testing. Previous studies indicated that irritant SLS reactivity may be related to individual factors such as age and sex. As these factors are, in turn, among the important predictors of contact allergy to many allergens, e.g. summarized in the 'MOAHLFA index', the impact of the MOAHLFA factors on irritant SLS patch test reactivity, and thus a potential for confounding, was assessed in the 5971 participating patients. As a result of 2 logistic regression analyses with an irritant reaction to 0.25% and 0.5% SLS, respectively, as outcome, male sex was identified as a relatively weak but significant risk factor (OR 1.38), while age 40 years or older was an even weaker risk factor (OR 1.22 and 1.15, respectively). Upon detailed analysis, no clear age gradient could, however, be identified. 1-day exposure time almost halved the odds of an irritant SLS reaction. In conclusion, this type of SLS patch test can be regarded as robust, indicating individual irritability relatively independent from the individual factors analysed here.

Developmental dysplasia of the hip: addressing evidence gaps with a multicentre prospective international study.

PubMed

Schaeffer, Emily K; Study Group, Ihdi; Mulpuri, Kishore

2018-05-07

There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH). Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers. To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest. This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes. There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6-8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age. Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age. Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.

Efficacy and safety of acarbose in the treatment of Type 1 diabetes mellitus: a placebo-controlled, double-blind, multicentre study.

PubMed

Riccardi, G; Giacco, R; Parillo, M; Turco, S; Rivellese, A A; Ventura, M R; Contadini, S; Marra, G; Monteduro, M; Santeusanio, F; Brunetti, P; Librenti, M C; Pontiroli, A E; Vedani, P; Pozza, G; Bergamini, L; Bianchi, C

1999-03-01

The aim of the study was to evaluate the efficacy and safety of acarbose in patients with Type 1 diabetes mellitus (DM). A multicentre double-blind, randomized, placebo-controlled study was performed. After a 6-week run-in, 121 patients were randomized to acarbose or placebo and to high- or low-fibre diet for 24 weeks. Acarbose dose was 50 mg t.d.s. for the first 2 weeks and 100 mg t.d.s. for the subsequent weeks. At the end of 24 weeks of treatment the intention to treat analysis showed that acarbose compared with placebo decreased 2 h postprandial plasma glucose levels (12.23 +/- 0.83 vs. 14.93 +/- 0.87 mmol/l; F = 6.1, P < 0.02) (least square means +/- SEM). No significant effect of acarbose was recorded on HbA1c or on the number of hypoglycaemic episodes. The effect of acarbose on blood glucose control was not influenced by the amount of carbohydrate and/or fibre intake. The incidence of adverse events were 75% and 39% in acarbose and placebo groups, respectively; they were mild and confined to the gastrointestinal tract. The use of acarbose in combination with insulin reduces postprandial plasma glucose levels in Type 1 diabetic patients who are not satisfactorily controlled with insulin alone but without significant effect on HbA1c.

Clinical and diagnosis characteristics of breast cancers in women with a history of radiotherapy in the first 30years of life: A French multicentre cohort study.

PubMed

Demoor-Goldschmidt, C; Supiot, S; Oberlin, O; Helfre, S; Vigneron, C; Brillaud-Meflah, V; Bernier, V; Laprie, A; Ducassou, A; Claude, L; Mahé, M A; de Vathaire, F

2017-08-01

Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC. A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage. Copyright © 2017. Published by Elsevier B.V.

Treatment of anthracycline extravasation with Savene (dexrazoxane): results from two prospective clinical multicentre studies.

PubMed

Mouridsen, H T; Langer, S W; Buter, J; Eidtmann, H; Rosti, G; de Wit, M; Knoblauch, P; Rasmussen, A; Dahlstrøm, K; Jensen, P B; Giaccone, G

2007-03-01

The purpose of this study was to assess the efficacy and tolerability of i.v. dexrazoxane [Savene (EU), Totect (US)] as acute antidote in biopsy-verified anthracycline extravasation. Two prospective, open-label, single-arm, multicentre studies in patients with anthracycline extravasation were carried out. Patients with fluorescence-positive tissue biopsies were treated with a 3-day schedule of i.v. dexrazoxane (1000, 1000, and 500 mg/m(2)) starting no later than 6 h after the incident. Patients were assessed for efficacy (the possible need for surgical resection) and toxicity during the treatment period and regularly for the next 3 months. In 53 of 54 (98.2%) patients assessable for efficacy, the treatment prevented surgery-requiring necrosis. One patient (1.8%) required surgical debridement. Thirty-eight patients (71%) were able to continue their scheduled chemotherapy without postponement. Twenty-two patients (41%) experienced hospitalisation due to the extravasation. Mild pain (10 patients; 19%) and mild sensory disturbances (nine patients; 17%) were the most frequent sequelae. Haematologic toxicity was common as expected from the fact that the extravasation occurred during a chemotherapy course. Other toxic effects were transient elevation of alanine aminotransferases, nausea, and local pain at the dexrazoxane injection site. Dexrazoxane proved to be an effective and well-tolerated acute treatment with only one out of 54 assessable patients requiring surgical resection (1.8%).

Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study

PubMed Central

Yuan, Ziwen; Wang, Bo; Li, Feijiang; Wang, Jing; Zhi, Jin; Luo, Erping; Liu, Zhirong; Zhao, Gang

2015-01-01

Introduction The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China. Methods and analysis This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset. Ethics and dissemination The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes. Trial registration number NCT02088346 (12 March 2014). PMID:25979867

[Prevalence of X-ray signs of femoroacetabular impingement in Mexican population].

PubMed

Gutiérrez-Ramos, R; Ávalos-Calderón, S A; Bahena-Peniche, L A

2017-01-01

Femoroacetabular impingement (FAI) is a suggested diagnosis for pain in the hip in the absence of other apparent causes. It is thought to be a cause of progressive arthrosis of the hip. Our objective was to determine the prevalence of radiographic data of FAI in the adult population without hip pathology over a period of six months. Analytical, observational, multicentric, ambispective and transverse study based on digital X-rays analysis. Measurements of the lateral center-edge angle of Wiberg, acetabular inclination, Tönnis angle and the neck shaft angle of the proximal femur were made; a pistol grip deformity of the femoral head, the triangular index and the shape of the coxofemoral joint were also evaluated. From a total of 212 hips evaluated, 104 were in males and 108 in females, with an average age of 42.81 years; 21 had a pistol grip deformity and a positive triangular index for cam type. The pincer type was found in 12 hips. In this multicentric study, the FAI cam type predominated in men on the right side; the pincer type predominated in women on the left side; this is similar to what has been reported in other populations. This study is limited by the wide variation in the femoral rotation; as an advantage, it was randomly carried out and provides some data on the prevalence of deformities of the hip, not previously registered.

CoDuSe group exercise programme improves balance and reduces falls in people with multiple sclerosis: A multi-centre, randomized, controlled pilot study.

PubMed

Carling, Anna; Forsberg, Anette; Gunnarsson, Martin; Nilsagård, Ylva

2017-09-01

Imbalance leading to falls is common in people with multiple sclerosis (PwMS). To evaluate the effects of a balance group exercise programme (CoDuSe) on balance and walking in PwMS (Expanded Disability Status Scale, 4.0-7.5). A multi-centre, randomized, controlled single-blinded pilot study with random allocation to early or late start of exercise, with the latter group serving as control group for the physical function measures. In total, 14 supervised 60-minute exercise sessions were delivered over 7 weeks. Pretest-posttest analyses were conducted for self-reported near falls and falls in the group starting late. Primary outcome was Berg Balance Scale (BBS). A total of 51 participants were initially enrolled; three were lost to follow-up. Post-intervention, the exercise group showed statistically significant improvement ( p = 0.015) in BBS and borderline significant improvement in MS Walking Scale ( p = 0.051), both with large effect sizes (3.66; -2.89). No other significant differences were found between groups. In the group starting late, numbers of falls and near falls were statistically significantly reduced after exercise compared to before ( p < 0.001; p < 0.004). This pilot study suggests that the CoDuSe exercise improved balance and reduced perceived walking limitations, compared to no exercise. The intervention reduced falls and near falls frequency.

Seroprevalence and risk factors for hepatitis C virus infection among blood donors in Serbia: A multicentre study.

PubMed

Mitrovic, Nikola; Delic, Dragan; Markovic-Denic, Ljiljana; Jovicic, Milica; Popovic, Natasa; Bojovic, Ksenija; Simonovic Babic, Jasmina; Svirtlih, Neda

2015-07-01

The epidemiological characteristics of hepatitis C virus (HCV) infection have not yet been described in Serbia. To determine the prevalence of anti-HCV-positive individuals among first-time blood donors and the risk factors for hepatitis C transmission. A multicentre case-control study nested within a prospective cohort study was conducted at 10 main transfusion centres in Serbia in 2013 and 27,160 blood donors who gave blood for the first time were included. Blood donors with confirmed anti-HCV positivity and seronegative controls were enrolled to determine the risk factors. Of 27,160 blood donors 52 were anti-HCV-positive; seroprevalence was 0.19%. By univariate analysis, marital status, educational level, drug use, previous transfusion, tattooing, non-use of condoms and number of sexual partners, were risk factors for hepatitis C. In the final multivariate analysis, three factors remained independently predictive: drug use, tattooing and previous blood transfusion. In total, 87.5% of cases had at least one of the risk factors for HCV transmission; 20.9% presumed that they knew when the infection occurred. HCV seroprevalence in Serbia is higher than in developed European countries. Preventive measures need to be directed towards drug use and tattooing facilities. The admission questionnaire for blood donors should be improved. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial)

PubMed Central

2011-01-01

Background Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. Methods/design In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. Conclusion The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. Trial Registration Number Netherlands Trial Register (NTR): NTR2579 PMID:21410949

Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY): essential study design and rationale of a randomised clinical multicentre trial.

PubMed

Lindhardt, Morten; Persson, Frederik; Currie, Gemma; Pontillo, Claudia; Beige, Joachim; Delles, Christian; von der Leyen, Heiko; Mischak, Harald; Navis, Gerjan; Noutsou, Marina; Ortiz, Alberto; Ruggenenti, Piero Luigi; Rychlik, Ivan; Spasovski, Goce; Rossing, Peter

2016-03-02

Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment in normoalbumuric patients have given mixed results. This might reflect that the large fraction of normoalbuminuric patients are not at risk of progression, thereby reducing power in previous studies. A specific risk classifier based on urinary proteomics (chronic kidney disease (CKD)273) has been shown to identify normoalbuminuric diabetic patients who later progressed to overt kidney disease, and may hold the potential for selection of high-risk patients for early intervention. Combining the ability of CKD273 to identify patients at highest risk of progression with prescription of preventive aldosterone blockade only to this high-risk population will increase power. We aim to confirm performance of CKD273 in a prospective multicentre clinical trial and test the ability of spironolactone to delay progression of early diabetic nephropathy. Investigator-initiated, prospective multicentre clinical trial, with randomised double-masked placebo-controlled intervention and a prospective observational study. We aim to include 3280 type 2 diabetic participants with normoalbuminuria. The CKD273 classifier will be assessed in all participants. Participants with high-risk pattern are randomised to treatment with spironolactone 25 mg once daily, or placebo, whereas, those with low-risk pattern will be observed without intervention other than standard of care. Treatment or observational period is 3 years.The primary endpoint is development of confirmed microalbuminuria in 2 of 3 first morning voids urine samples. The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy may pave the way for personalised medicine approaches in treatment of diabetes complications. NCT02040441; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Branched-Chain Amino Acids Are the Primary Limiting Amino Acids in the Diets of Endurance-Trained Men after a Bout of Prolonged Exercise.

PubMed

Kato, Hiroyuki; Suzuki, Katsuya; Bannai, Makoto; Moore, Daniel R

2018-05-09

The indicator amino acid oxidation (IAAO) method estimates the protein intake required to maximize whole-body protein synthesis and identify the daily protein requirement in a variety of populations. However, it is unclear whether the greater requirements for endurance athletes previously determined by the IAAO reflect an increased demand for all or only some amino acids. The aim of this study was to determine the primary rate-limiting amino acids in endurance-trained athletes after prolonged exercise, by measuring the oxidation of ingested [1-13C]phenylalanine in response to variable amino acid intake. Five endurance-trained men (means ± SDs: age, 26 ± 7 y; body weight, 66.9 ± 9.5 kg; maximal oxygen consumption, 63.3 ± 4.3 mL · kg-1 · min-1) performed 5 trials that involved 2 d of controlled diet (1.4 g protein · kg-1 · d-1) and running (10 km on day 1 and 5 km on day 2) prior to performing an acute bout of endurance exercise (20-km treadmill run) on day 3. During recovery on day 3, participants consumed test diets as 8 isocaloric hourly meals providing sufficient energy and carbohydrate but a variable amino acid intake. The test diets, consumed in random order, were deficient (BASE: 0.8 g · kg-1 · d-1) and sufficient (SUF; 1.75 g · kg-1 · d-1) amino acid diets modeled after egg protein, and BASE supplemented with branched-chain amino acids (BCAA diet; 1.03 g · kg-1 · d-1), essential amino acids (EAA diet; 1.23 g · kg-1 · d-1), or nonessential amino acids (NEAA diet; 1.75 g · kg-1 · d-1). Whole-body phenylalanine flux (Q), 13CO2 excretion (F13CO2), and phenylalanine oxidation (OX) were determined according to standard IAAO methodology. There was no effect of amino acid intake on Q (P = 0.43). F13CO2 was significantly (all P < 0.01) lower than BASE for the BCAA (∼32%), EAA (∼31%), and SUF (∼36%) diet treatments. F13CO2 for the NEAA diet was ∼18% lower than for BASE (P < 0.05) but ∼28% greater than for SUF (P < 0.05). OX was similarly decreased (∼24-41%) in all conditions compared with BASE (all P < 0.05). Our results suggest that the BCAAs may be the primary rate-liming amino acids in the greater daily protein requirement of endurance trained men. This trial was registered at clinicaltrial.gov as NCT02628249.

Histidine deficiency has a negative effect on lactational performance of dairy cows.

PubMed

Giallongo, F; Harper, M T; Oh, J; Parys, C; Shinzato, I; Hristov, A N

2017-04-01

A 10-wk randomized complete block design experiment with 24 Holstein cows was conducted to investigate the long-term effects of feeding a His-deficient diet on lactational performance of dairy cows. Cows were blocked by days in milk, milk yield, and parity, and randomly assigned to 1 of the following 2 treatments: (1) His-adequate diet [HAD; providing +166 g/d over metabolizable protein (MP) requirements, according to the National Research Council (2001) and digestible His (dHis) supply of 68 g/d, or 2.5% of MP requirements] and (2) His-deficient diet (HDD; +37 g/d over MP requirements and dHis supply of 49 g/d, or 1.9% of MP requirements). Both HAD and HDD were supplemented with rumen-protected (RP) Met and Lys supplying digestible Met and digestible Lys at 2.4 and 2.4% and 7.2 and 7.1% of MP requirements, respectively. At the end of the 10-wk experiment, HDD was supplemented with RPHis (HDD+RPHis; total dHis supply of 61 g/d, or 2.4% of MP requirements) for an additional 9 d. Dry matter intake (DMI; 25.4 and 27.1 kg/d, standard error of the mean = 0.41), yields of milk (37.6 and 40.5 kg/d, standard error of the mean = 0.62), protein and lactose, energy-corrected milk, and milk and plasma urea-N were decreased by HDD compared with HAD. Feed and energy-corrected milk feed efficiencies, milk fat, protein and lactose concentrations, body weight, and body condition score of the cows were not affected by treatment. Apparent total-tract digestibility of dry and organic matter, crude protein, and neutral detergent fiber, and excretion of urinary N and urea-N were decreased by HDD compared with HAD. Concentration of plasma leptin tended to be decreased for HDD compared with HAD. Plasma concentrations of EAA (His, Leu, Lys, Val) and carnosine decreased and total EAA tended to be decreased in cows fed HDD compared with HAD. Muscle concentrations of free His, Leu, and Val decreased and Gly and β-alanine tended to be increased by HDD compared with HAD. Cows fed HDD had a lower blood hemoglobin concentration than cows fed HAD. At the end of the 10-wk study, the 9-d supplementation of HDD with RPHis (i.e., HDD+RPHis) increased DMI and plasma His, and tended to increase energy-corrected milk yield and plasma carnosine, compared with HDD. In conclusion, feeding a diet deficient in dHis supplying adequate MP, digestible Met, and digestible Lys affected negatively lactational performance of dairy cows. These results confirm our previous findings that low dietary His supply can impair DMI, yields of milk and milk protein, and blood hemoglobin in dairy cows. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

PubMed

Zhao, Ling; Zhang, Fu-wen; Li, Ying; Wu, Xi; Zheng, Hui; Cheng, Lin-hao; Liang, Fan-rong

2011-03-24

In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial.

PubMed

van de Ven, J; Fransen, A F; Schuit, E; van Runnard Heimel, P J; Mol, B W; Oei, S G

2017-09-01

Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or implemented, repetitive training sessions every three months seem therefore recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ - The LORD study.

PubMed

Elshof, Lotte E; Tryfonidis, Konstantinos; Slaets, Leen; van Leeuwen-Stok, A Elise; Skinner, Victoria P; Dif, Nicolas; Pijnappel, Ruud M; Bijker, Nina; Rutgers, Emiel J Th; Wesseling, Jelle

2015-08-01

The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The self-assessed psychological comorbidities of prurigo in European patients: A multi-centre study in 13 countries.

PubMed

Brenaut, Emilie; Halvorsen, Jon Anders; Dalgard, Florence J; Lien, Lars; Balieva, Flora; Sampogna, Francesca; Linder, Dennis; Evers, Andrea W M; Jemec, Gregor B E; Gieler, Uwe; Szepietowski, Jacek; Poot, Françoise; Altunay, Ilknur K; Finlay, Andrew Y; Salek, Sam S; Szabo, Csanad; Lvov, Andrey; Marron, Servando E; Tomas-Aragones, Lucia; Kupfer, Jörg; Misery, Laurent

2018-06-19

Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. The aim of this study was to assess the psychological burden of prurigo in patients of European countries. In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10/27 (37%) suffered from anxiety and 8/27 (29%) from depression. Suicidal ideation was reported by 5/27 (19%) of patients, and for 4 out of these 5 patients, suicidal ideation was related to their skin disease. These frequencies were higher than in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers for example). The impact on quality of life was severe, with a mean DLQI of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intrathecal baclofen therapy in paediatrics: a study protocol for an Australian multicentre, 10-year prospective audit

PubMed Central

Stewart, Kirsty; Hutana, Gavin; Kentish, Megan

2017-01-01

Introduction Increasing clinical use of Intrathecal baclofen (ITB) in Australian tertiary paediatric hospitals, along with the need for standardised assessment and reporting of adverse events, saw the formation of the Australian Paediatric ITB Research Group (APIRG). APIRG developed a National ITB Audit tool designed to capture clinical outcomes and adverse events data for all Australian children and adolescents receiving ITB therapy. Methods and analysis The Australian ITB Audit is a 10 year, longitudinal, prospective, clinical audit collecting all adverse events and assessment data across body functions and structure, participation and activity level domains of the ICF. Data will be collected at baseline, 6 and 12 months with ongoing capture of all adverse event data. This is the first Australian study that aims to capture clinical and adverse event data from a complete population of children with neurological impairment receiving a specific intervention between 2011 and 2021. This multi-centre study will inform ITB clinical practice in children and adolescents, direct patient selection, record and aid decision making regarding adverse events and investigate the impact of ITB therapy on family and patient quality of life. Ethics and dissemination This project was approved by the individual Human Research Ethics committees at the six Australian tertiary hospitals involved in the study. Results will be published in various peer reviewed journals and presented at national and international conferences. Trial registration number ACTRN 12610000323022; Pre-results. PMID:28637739

Prospective evaluation of the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) in a multicentre setting.

PubMed

Castel, V; García-Miguel, P; Cañete, A; Melero, C; Navajas, A; Ruíz-Jiménez, J I; Navarro, S; Badal, M D

1999-04-01

The aim of this study was to classify prospectively a series of neuroblastoma tumours according to the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) and to evaluate the difficulties and pitfalls involved in a multicentre setting. Each hospital provided their data for central review. The surgical procedures and their complications were reported. Kaplan-Meier estimates of survival and event-free survival were calculated according to stage and response to therapy. From June 1992 to December 1996, 194 patients were included in the study, with a mean age of 2 years. Initial studies were performed according to INSS recommendations without major problems. INSS stage was correctly applied to all patients except for 9 (95%). Post-operative complications were observed in 15 patients (8.3%). Response to therapy (INRC) was studied in 63 stage 4 patients, 11 of whom were not classified correctly (17%). Differences in survival according to stage (INSS) and group of response to therapy (INRC) were statistically significant (P < 0.001). In conclusion the INSS was easy to use and separated different prognostic groups. Surgical complications and mortality did not increase in this series because of using the INSS. The feasibility of INRC was evaluated in a small series of stage 4 patients and the designation of response was problematic in a relatively high proportion of cases. The prognostic value of the different responses was highly significant, but less informative than had been hoped for.

[Cinacalcet in the management of normocalcaemic secondary hyperparathyroidism after kidney transplantation: one-year follow-up multicentre study].

PubMed

Torregrosa, Josep V; Morales, Enrique; Díaz, Juan M; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel A; Rodríguez-Benot, Alberto; Rodríguez-García, Minerva; López-Jiménez, Verónica; Gutiérrez-Dalmau, Álex; Jimeno, Luisa; Pérez-Sáez, M José; Romero, Rafael; Gómez-Alamillo, Carlos

2014-01-01

The effect of cinacalcet in patients with persistent secondary hyperparathyroidism (SHPT) after kidney transplantation (RT) has mainly been reported in patients with secondary hypercalcaemia. Our objective was to assess the long-term effect of cinacalcet on patients with a RT and normocalcaemic SHPT. A one-year multicentre, observational, retrospective study that included kidney recipients with SHPT (intact parathyroid hormone [iPTH] >120 pg/ml) and calcium levels within the normal range (8.4-10.2 mg/dl). Patients began treatment with cinacalcet in clinical practice. 32 patients with a mean age (standard deviation [SD]) of 54 (11) years, 56% male, were included in the study. Treatment with cinacalcet began a median of 16 months after RT (median dose of 30 mg/day). Levels of iPTH decreased from a median (P25, P75) of 364 (220, 531) pg/ml at the start of the study to 187 (98, 320) after 6 months (48.6% reduction, P=.001) and to 145 (91, 195) after 12 months (60.2% reduction, P=.001), without there being changes in calcium and phosphorus levels (P=.214 and P=.216, respectively). No changes were observed in kidney function or anti-calcineuric drug levels. 3.1% of patients discontinued cinacalcet due to intolerance and 6.2% due to a lack of efficacy. In patients with normocalcaemic SHPT after RT, cinacalcet improves the control of serum PTH values without causing changes to calcaemia, phosphataemia or kidney function. Cinacalcet showed good tolerability.

The psychosocial burden of hand eczema: Data from a European dermatological multicentre study.

PubMed

Marron, Servando E; Tomas-Aragones, Lucia; Navarro-Lopez, Jorge; Gieler, Uwe; Kupfer, Jörg; Dalgard, Florence J; Lien, Lars; Finlay, Andrew Y; Poot, Françoise; Linder, Dennis; Szepietowski, Jacek C; Misery, Laurent; Jemec, Gregor B E; Romanov, Dmitry; Sampogna, Francesca; Szabo, Csanad; Altunay, Ilknur K; Spillekom-van Koulil, Saskia; Balieva, Flora; Ali, Faraz M; Halvorsen, Jon A; Marijuan, Pedro C

2018-06-01

The essential physical role, visibility and social importance of the hands place a major psychological burden on patients with hand eczema. The aim of this study was to identify the psychological, social and clinical characteristics of patients with hand eczema, in particular the prevalences of depression, anxiety, suicidal ideation, and comorbidities. Data on patients with hand eczema were analysed from a large European multicentre study conducted with dermatology outpatients from 13 countries. Groups of patients and controls were compared to analyse the psychological burden of hand eczema. Female patients with hand eczema had higher Hospital Anxiety and Depression Scale (HADS) scores for anxiety (n = 86, median = 7.0) than controls (n = 900, median = 5.0, P = .02), and for depression (median = 4.0) than controls (3.0, P < .001). Patients with high suicidal ideation, with low socioeconomic status and who were widowed or divorced were more likely to fulfil the HADS criteria for anxiety [odds ratio (OR) > 1, P = .038, P < .001, and P < .001, respectively]. The median Dermatology Life Quality Index score was 7.0 (n = 68). This study identifies a specific psychological burden experienced by hand eczema patients, highlighting the need for focused psychosocial interventions. Physicians in particular should be aware of the need to identify anxiety and depression in female patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

International Rare Histiocytic Disorders Registry (IRHDR)

ClinicalTrials.gov

2018-04-18

Rare Histiocytic Disorders (RHDs); Juvenile Xanthogranuloma (JXG); Reticulohistiocytoma (Epithelioid Histiocytoma); Xanthoma Disseminatum (XD); Multicentric Reticulohistiocytosis (MRH); Systemic Juvenile Xanthogranuloma; Erdheim-Chester Disease (ECD); Multi-system Rosai-Dorfman Disease (RDD)

Outcomes after resection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Kinoshita, Masahiko; Hamano, Genya; Ito, Tokuji; Koda, Masaki; Aota, Takanori; Yamamoto, Takatsugu; Terajima, Hiroaki; Tachiyama, Gorou; Yamada, Terumasa; Nakamori, Shoji; Arimoto, Akira; Fujikawa, Masahiro; Tomimaru, Yoshito; Sugawara, Yasuhiko; Nakagawa, Kei; Unno, Michiaki; Mizuguchi, Toru; Takenaka, Kenji; Kimura, Koichi; Shirabe, Ken; Saiura, Akio; Uesaka, Katsuhiko; Taniguchi, Hiroki; Fukuda, Akira; Chong, Ja-Mun; Kuwae, Yuko; Ohsawa, Masahiko; Sato, Yasunori; Nakanuma, Yasuni

2016-09-01

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Glutamine--from conditionally essential to totally dispensable?

PubMed

Wernerman, Jan

2014-07-02

Recently a large multicentre randomised controlled trial in critically ill patients reported harm to the patients given supplementary glutamine. In the original publication, no explanation was offered for why this result was obtained; a large number of studies have reported beneficial effects or no effect, but never before reported harm. These results have been commented upon in a number of communications. Now some of the authors of the multicentre randomised controlled trial present a review and meta-analysis of glutamine supplementation, and the discrepancy of results is suggested to relate to intravenous administration to patients of supplementary glutamine via parenteral nutrition or a combination of enteral and parenteral nutrition in contrast to enteral administration of supplementation or a combination of enteral and parenteral supplementation. To explain results by epidemiological means only, by combining results into a meta-analysis, is perhaps not the best way to explain mechanisms behind results. Meta-analyses are primarily hypothesis generating. Launching treatment without a solid mechanistic explanation is always risky. Glutamine supplementation of the critically ill comes into that category. Now we will all have to do our homework and try to understand whether supplementation or omission of glutamine for patients fed parenterally is a good idea or not.

Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction

PubMed Central

Nordlund, David; Klug, Gert; Heiberg, Einar; Koul, Sasha; Larsen, Terje H.; Hoffmann, Pavel; Metzler, Bernhard; Erlinge, David; Atar, Dan; Aletras, Anthony H.; Carlsson, Marcus; Engblom, Henrik; Arheden, Håkan

2016-01-01

Aims Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings. Methods and results A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1–8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r2 = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). Conclusion In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials. PMID:27002140

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.