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Global Response (global + response)
Selected AbstractsRelationship between various clinical outcome assessments in patients with blepharospasm,MOVEMENT DISORDERS, Issue 3 2009Joseph Jankovic MD Abstract The objective was to analyze the metric properties of the Jankovic Rating Scale (JRS) and a self-rating patient response outcome scale, the Blepharospasm Disability Index (BSDI©), in blepharospasm patients. Data from a randomized, double-blind, active-control clinical trial in 300 patients with blepharospasm treated with either botulinum toxin type A (Botox®) or NT201 (Xeomin®) were used to evaluate the metric properties of the JRS and the BSDI compared with the Patient Evaluation of Global Response (PEGR) and Global Assessment Scale (GAS). The internal consistency of the BSDI was high, Cronbach's Alpha = 0.88, and the retest reliability of the BSDI single items was adequate, Spearman's rank coefficient = 0.453 < r < 0.595. The correlation between JRS sum score and BSDI weighted mean score was r = 0.487 (baseline) and r = 0.737 (control visit), respectively. Using the GAS and PEGR, the results suggest that a change of 2 points in the JRS and of 0.7 points in the BSDI are clinically meaningful. JRS and BSDI are objective indicators of clinical efficacy as suggested by their good validity when compared with physicians' and patients' rating scales. Both, JRS and BSDI, can be used to reliably assess blepharospasm in treatment trials. © 2008 Movement Disorder Society [source] An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczemaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007S.C. Weatherhead Summary Background, Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. Objectives, We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. Methods, All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2·5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. Results, On average, disease activity improved by 52% from baseline (95% confidence interval 45,60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as ,marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. Conclusions, We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted. [source] Localization analysis in softening RC frame structuresEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 2 2003Ali R. Khaloo Abstract This paper discusses the sensitivity of softening reinforced concrete frame structures to the changes in input ground motion and investigates the possibility of localizations for this type of structure in static and dynamic analysis. A finite element model is used in which the sections resisting force are calculated using a proposed differential hysteretic model. This model is especially developed for modelling softening behaviour under cyclic loading. To obtain parameters of the differential model the moment,curvature of each section is evaluated using a microplane constitutive law for concrete and bi-linear elasto-plastic law for reinforcements. The capability of the procedure is verified by comparing results with available experimental data at element level, which shows good accuracy of the procedure. The effect of possible changes in ground motion is assessed using a non-stationary Kanai,Tajimi process. This process is used to generate ground motions with approximately the same amplitude and frequency content evolution as those of base ground motion. The possibility of localization in static and dynamic loading is investigated using two structures. A measure for the possibility of localization in code-designed structures is obtained. This study indicates that localization may occur in ordinary moment-resisting structures located in high seismic zones. Localization may result in substantial drift in global response and instability due to P,, effect. Also, it is shown that the structure becomes very sensitive to the input ground motion. It is concluded that allowance by some design codes of the use of ordinary moment-resisting frames in regions with high seismicity should be revised or improvements should be made in the detailing requirements at critical sections of these structures. Copyright © 2002 John Wiley & Sons, Ltd. [source] Influences of species, latitudes and methodologies on estimates of phenological response to global warmingGLOBAL CHANGE BIOLOGY, Issue 9 2007CAMILLE PARMESANArticle first published online: 14 AUG 200 Abstract New analyses are presented addressing the global impacts of recent climate change on phenology of plant and animal species. A meta-analysis spanning 203 species was conducted on published datasets from the northern hemisphere. Phenological response was examined with respect to two factors: distribution of species across latitudes and taxonomic affiliation or functional grouping of target species. Amphibians had a significantly stronger shift toward earlier breeding than all other taxonomic/functional groups, advancing more than twice as fast as trees, birds and butterflies. In turn, butterfly emergence or migratory arrival showed three times stronger advancement than the first flowering of herbs, perhaps portending increasing asynchrony in insect,plant interactions. Response was significantly stronger at higher latitudes where warming has been stronger, but latitude explained < 4% of the variation. Despite expectation, latitude was not yet an important predictor of climate change impacts on phenology. The only two previously published estimates of the magnitude of global response are quite different: 2.3 and 5.1 days decade,1 advancement. The scientific community has assumed this difference to be real and has attempted to explain it in terms of biologically relevant phenomena: specifically, differences in distribution of data across latitudes, taxa or time periods. Here, these and other possibilities are explored. All analyses indicate that the difference in estimated response is primarily due to differences between the studies in criteria for incorporating data. It is a clear and automatic consequence of the exclusion by one study of data on ,stable' (nonresponsive) species. Once this is accounted for, the two studies support each other, generating similar conclusions despite analyzing substantially nonoverlapping datasets. Analyses here on a new expanded dataset estimate an overall spring advancement across the northern hemisphere of 2.8 days decade,1. This is the first quantitative analysis showing that data-sampling methodologies significantly impact global (synthetic) estimates of magnitude of global warming response. [source] On the L2 and the H1 couplings for an overlapping domain decomposition method using Lagrange multipliersINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 3 2007P.-A. Guidault Abstract In this paper, a comparison of the L2 and the H1 couplings is made for an overlapping domain decomposition method using Lagrange multipliers. The analysis of the local equations arising from the formulation of the coupling of two mechanical models shows that continuous weight functions are required for the L2 coupling term whereas both discontinuous and continuous weight functions can be used for the H1 coupling. The choice of the Lagrange multiplier space is discussed and numerically studied. The paper ends with some numerical examples of an end-loaded cantilever beam and a cracked plate under tension and shear. It is shown that the continuity enforced with the H1 coupling leads to a link with a flexibility that can be beneficial for coupling a very coarse mesh with a very fine one. To limit the effect of the volume coupling on the global response, a narrow coupling zone is recommended. In this case, volume coupling tends to a surface coupling, especially with a L2 coupling. Copyright © 2006 John Wiley & Sons, Ltd. [source] Impact of global warming on ENSO variability using the coupled giss GCM/ZC modelINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 10 2006Dr. Timothy Eichler Research Scientist Abstract This study uses a hybrid coupled model (referred to as the general-circulation model (GCM)/Zebiak/Cane (ZC) model), which consists of the Goddard Institute for Space Studies' (GISS) Atmospheric general-circulation model (AGCM) coupled to the oceanic component of the ZC intermediate model to assess the impact of global warming on El Niño behavior, with and without the influence of heat introduced from the subtropical Pacific (via subtropical cell (STC) pathway). The baseline GCM/ZC model produces El Niño variability with a two year periodicity and an amplitude of approximately half the magnitude of observed El Niño. The GCM/ZC model also produces an appropriate atmospheric global response to El Niño/southern oscillation (ENSO) as shown by composites of 500 hPa heights, sea-level pressure (SLP), 200 hPa wind, and precipitation during El Niño and La Niña periods. To evaluate the importance of global warming on ENSO variability, 2× CO2 and 4× CO2 transient simulations were done increasing the atmospheric CO2 one percent per year, then extending the runs for an additional 70 years to obtain equilibrium climates for each run. An additional set of global-warming simulations was run after including a STC parameterization generated by computing 5-year running means of the sea-surface temperature (SST) difference between a transient run and the 1× CO2 GCM/ZC run at the anticipated subduction zones (160,130°W, 20,40°N and 20,44°S, 160,130°W) and adding it to the base of the equatorial mixed-layer of the ZC model with a time lag of 15 years. This effectively alters the vertical temperature gradient of the ZC model, which affects SST via upwelling. Two features of the GCM/ZC response to global warming are emphasized. Firstly, the inclusion of the STC results in a major redistribution of heat across the equatorial Pacific, leading to an El Niño-like response in the final equilibrium solution with less variability about the mean. The global warming aspect due to the El Niño-like response results in a positive feedback on global warming, which causes a higher global surface-air temperature (SAT) than identical transient simulations without inclusion of the STC. Secondly, including the STC effect produces a far greater magnitude of global ENSO-like impact because of the reduction of, or even the reversal of, the equatorial Pacific longitudinal SST gradient. The implications of such an extreme climate scenario are discussed. Copyright © 2006 Royal Meteorological Society [source] Meta-analysis: the effects of placebo treatment on gastro-oesophageal reflux diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010F. Cremonini Aliment Pharmacol Ther 2010; 32: 29,42 Summary Background, There appears to be a significant placebo response rate in clinical trials for gastro-oesophageal reflux disease. Little is known about the determinants and the circumstances associated with placebo response in the treatment of gastro-oesophageal reflux disease (GERD). Aims, To estimate the magnitude of the placebo response rate in randomized controlled trials for GERD and to identify factors that influence this response. Methods, A meta-analysis of randomized, double-blind, placebo-controlled trials, published in English language, which included >20 patients with GERD, treated with either a proton pump inhibitor or H2 -receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched, considering only studies that reported a global response for ,heartburn'. Results, A total of 24 studies included 9989 patients with GERD. The pooled odds ratio (OR) for response to active treatment vs. placebo was 3.71 (95% CI: 2.78,4.96). The pooled estimate of the overall placebo response was 18.85% (range 2.94%,47.06%). Patients with erosive oesophagitis had a non-significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; P = 0.246). Placebo response was significantly lower in studies of PPI therapy vs. studies of H2 RAs (14.51% vs. 24.69%, respectively; P = 0.05). Conclusions, The placebo response rate in randomized controlled trials for GERD is substantial. A lower placebo response was associated with the testing of PPIs, but not the presence of erosive oesophagitis. [source] Defining the disulphide stress response in Streptomyces coelicolor A3(2): identification of the ,R regulonMOLECULAR MICROBIOLOGY, Issue 4 2001Mark S. B. Paget In the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2), the thiol-disulphide status of the hyphae is controlled by a novel regulatory system consisting of a sigma factor, ,R, and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphide bond formation in RsrA, which causes it to lose affinity for ,R, thereby releasing ,R to activate transcription of the thioredoxin operon, trxBA. Here, we exploit a preliminary consensus sequence for ,R target promoters to identify 27 new ,R target genes and operons, thereby defining the global response to disulphide stress in this organism. Target genes related to thiol metabolism encode a second thioredoxin (TrxC), a glutaredoxin-like protein and enzymes involved in the biosynthesis of the low-molecular-weight thiol-containing compounds cysteine and molybdopterin. In addition, the level of the major actinomycete thiol buffer, mycothiol, was fourfold lower in a sigR null mutant, although no candidate mycothiol biosynthetic genes were identified among the ,R targets. Three ,R target genes encode ribosome-associated products (ribosomal subunit L31, ppGpp synthetase and tmRNA), suggesting that the translational machinery is modified by disulphide stress. The product of another ,R target gene was found to be a novel RNA polymerase-associated protein, RbpA, suggesting that the transcriptional machinery may also be modified in response to disulphide stress. We present DNA sequence evidence that many of the targets identified in S. coelicolor are also under the control of the ,R homologue in the actinomycete pathogen Mycobacterium tuberculosis. [source] Insights into yeast adaptive response to the agricultural fungicide mancozeb: A toxicoproteomics approachPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2009Pedro M. Santos Abstract Toxicogenomics has the potential to elucidate gene,environment interactions to identify genes that are affected by a particular chemical at the early stages of the toxicological response and to establish parallelisms between different organisms. The fungicide mancozeb, widely used in agriculture, is an ethylene-bis-dithiocarbamate complex with manganese and zinc. Exposure to this pesticide has been linked to the development of idiopathic Parkinson's disease and cancer. Given that many signalling pathways and their molecular components are substantially conserved among eukaryotic organisms, we used Saccharomyces cerevisiae to get insights into the molecular mechanisms of mancozeb toxicity and adaptation based on expression proteomics. The early global response to mancozeb was analysed by quantitative proteomics using 2-DE. The target genes (e.g. TSA1, TSA2, SOD1, SOD2, AHP1, GRE2, GRX1, CYS3, PRE3, PRE6, PRE8, PRE9, EFT1, RPS5, TIF11, HSP31, HSP26, HSP104, HSP60, HSP70 -family) and the putative main transcription activators (e.g. Yap1, Msn2/Msn4, Met4, Hsf1, Aft1, Pdr1, Skn7, Rpn4p, Gcn4) of the complex mancozeb-induced expression changes are related with yeast response to stress, in particular to oxidative stress, protein translation initiation and protein folding, disassembling of protein aggregates and degradation of damaged proteins. Our results also suggest that this study provided powerful indications that may be useful to expand the knowledge obtained in yeast not only to the global response to mancozeb toxicity in phytopathogenic fungi but also to humans. [source] The global response to tropical heating in the Madden,Julian oscillation during the northern winterTHE QUARTERLY JOURNAL OF THE ROYAL METEOROLOGICAL SOCIETY, Issue 601 2004Adrian J. Matthews Abstract A life cycle of the Madden,Julian oscillation (MJO) was constructed, based on 21 years of outgoing long-wave radiation data. Regression maps of NCEP,NCAR reanalysis data for the northern winter show statistically significant upper-tropospheric equatorial wave patterns linked to the tropical convection anomalies, and extratropical wave patterns over the North Pacific, North America, the Atlantic, the Southern Ocean and South America. To assess the cause of the circulation anomalies, a global primitive-equation model was initialized with the observed three-dimensional (3D) winter climatological mean flow and forced with a time-dependent heat source derived from the observed MJO anomalies. A model MJO cycle was constructed from the global response to the heating, and both the tropical and extratropical circulation anomalies generally matched the observations well. The equatorial wave patterns are established in a few days, while it takes approximately two weeks for the extratropical patterns to appear. The model response is robust and insensitive to realistic changes in damping and basic state. The model tropical anomalies are consistent with a forced equatorial Rossby,Kelvin wave response to the tropical MJO heating, although it is shifted westward by approximately 20° longitude relative to observations. This may be due to a lack of damping processes (cumulus friction) in the regions of convective heating. Once this shift is accounted for, the extratropical response is consistent with theories of Rossby wave forcing and dispersion on the climatological flow, and the pattern correlation between the observed and modelled extratropical flow is up to 0.85. The observed tropical and extratropical wave patterns account for a significant fraction of the intraseasonal circulation variance, and this reproducibility as a response to tropical MJO convection has implications for global medium-range weather prediction. Copyright © 2004 Royal Meteorological Society [source] | |||||||||||||||||||