WorldWideScience

Sample records for single trial analysis

  1. Artificial bee colony algorithm for single-trial electroencephalogram analysis.

    Science.gov (United States)

    Hsu, Wei-Yen; Hu, Ya-Ping

    2015-04-01

    In this study, we propose an analysis system combined with feature selection to further improve the classification accuracy of single-trial electroencephalogram (EEG) data. Acquiring event-related brain potential data from the sensorimotor cortices, the system comprises artifact and background noise removal, feature extraction, feature selection, and feature classification. First, the artifacts and background noise are removed automatically by means of independent component analysis and surface Laplacian filter, respectively. Several potential features, such as band power, autoregressive model, and coherence and phase-locking value, are then extracted for subsequent classification. Next, artificial bee colony (ABC) algorithm is used to select features from the aforementioned feature combination. Finally, selected subfeatures are classified by support vector machine. Comparing with and without artifact removal and feature selection, using a genetic algorithm on single-trial EEG data for 6 subjects, the results indicate that the proposed system is promising and suitable for brain-computer interface applications. © EEG and Clinical Neuroscience Society (ECNS) 2014.

  2. Enhanced brainstem and cortical evoked response amplitudes: single-trial covariance analysis.

    Science.gov (United States)

    Galbraith, G C

    2001-06-01

    The purpose of the present study was to develop analytic procedures that improve the definition of sensory evoked response components. Such procedures could benefit all recordings but would especially benefit difficult recordings where many trials are contaminated by muscle and movement artifacts. First, cross-correlation and latency adjustment analyses were applied to the human brainstem frequency-following response and cortical auditory evoked response recorded on the same trials. Lagged cross-correlation functions were computed, for each of 17 subjects, between single-trial data and templates consisting of the sinusoid stimulus waveform for the brainstem response and the subject's own smoothed averaged evoked response P2 component for the cortical response. Trials were considered in the analysis only if the maximum correlation-squared (r2) exceeded .5 (negatively correlated trials were thus included). Identical correlation coefficients may be based on signals with quite different amplitudes, but it is possible to assess amplitude by the nonnormalized covariance function. Next, an algorithm is applied in which each trial with negative covariance is matched to a trial with similar, but positive, covariance and these matched-trial pairs are deleted. When an evoked response signal is present in the data, the majority of trials positively correlate with the template. Thus, a residual of positively correlated trials remains after matched covariance trials are deleted. When these residual trials are averaged, the resulting brainstem and cortical responses show greatly enhanced amplitudes. This result supports the utility of this analysis technique in clarifying and assessing evoked response signals.

  3. Single-visit or multiple-visit root canal treatment: systematic review, meta-analysis and trial sequential analysis.

    Science.gov (United States)

    Schwendicke, Falk; Göstemeyer, Gerd

    2017-02-01

    Single-visit root canal treatment has some advantages over conventional multivisit treatment, but might increase the risk of complications. We systematically evaluated the risk of complications after single-visit or multiple-visit root canal treatment using meta-analysis and trial-sequential analysis. Controlled trials comparing single-visit versus multiple-visit root canal treatment of permanent teeth were included. Trials needed to assess the risk of long-term complications (pain, infection, new/persisting/increasing periapical lesions ≥1 year after treatment), short-term pain or flare-up (acute exacerbation of initiation or continuation of root canal treatment). Electronic databases (PubMed, EMBASE, Cochrane Central) were screened, random-effects meta-analyses performed and trial-sequential analysis used to control for risk of random errors. Evidence was graded according to GRADE. 29 trials (4341 patients) were included, all but 6 showing high risk of bias. Based on 10 trials (1257 teeth), risk of complications was not significantly different in single-visit versus multiple-visit treatment (risk ratio (RR) 1.00 (95% CI 0.75 to 1.35); weak evidence). Based on 20 studies (3008 teeth), risk of pain did not significantly differ between treatments (RR 0.99 (95% CI 0.76 to 1.30); moderate evidence). Risk of flare-up was recorded by 8 studies (1110 teeth) and was significantly higher after single-visit versus multiple-visit treatment (RR 2.13 (95% CI 1.16 to 3.89); very weak evidence). Trial-sequential analysis revealed that firm evidence for benefit, harm or futility was not reached for any of the outcomes. There is insufficient evidence to rule out whether important differences between both strategies exist. Dentists can provide root canal treatment in 1 or multiple visits. Given the possibly increased risk of flare-ups, multiple-visit treatment might be preferred for certain teeth (eg, those with periapical lesions). Published by the BMJ Publishing Group Limited

  4. Spatiotemporal analysis of single-trial EEG of emotional pictures based on independent component analysis and source location

    Science.gov (United States)

    Liu, Jiangang; Tian, Jie

    2007-03-01

    The present study combined the Independent Component Analysis (ICA) and low-resolution brain electromagnetic tomography (LORETA) algorithms to identify the spatial distribution and time course of single-trial EEG record differences between neural responses to emotional stimuli vs. the neutral. Single-trial multichannel (129-sensor) EEG records were collected from 21 healthy, right-handed subjects viewing the emotion emotional (pleasant/unpleasant) and neutral pictures selected from International Affective Picture System (IAPS). For each subject, the single-trial EEG records of each emotional pictures were concatenated with the neutral, and a three-step analysis was applied to each of them in the same way. First, the ICA was performed to decompose each concatenated single-trial EEG records into temporally independent and spatially fixed components, namely independent components (ICs). The IC associated with artifacts were isolated. Second, the clustering analysis classified, across subjects, the temporally and spatially similar ICs into the same clusters, in which nonparametric permutation test for Global Field Power (GFP) of IC projection scalp maps identified significantly different temporal segments of each emotional condition vs. neutral. Third, the brain regions accounted for those significant segments were localized spatially with LORETA analysis. In each cluster, a voxel-by-voxel randomization test identified significantly different brain regions between each emotional condition vs. the neutral. Compared to the neutral, both emotional pictures elicited activation in the visual, temporal, ventromedial and dorsomedial prefrontal cortex and anterior cingulated gyrus. In addition, the pleasant pictures activated the left middle prefrontal cortex and the posterior precuneus, while the unpleasant pictures activated the right orbitofrontal cortex, posterior cingulated gyrus and somatosensory region. Our results were well consistent with other functional imaging

  5. Selectivity of N170 for visual words in the right hemisphere: Evidence from single-trial analysis.

    Science.gov (United States)

    Yang, Hang; Zhao, Jing; Gaspar, Carl M; Chen, Wei; Tan, Yufei; Weng, Xuchu

    2017-08-01

    Neuroimaging and neuropsychological studies have identified the involvement of the right posterior region in the processing of visual words. Interestingly, in contrast, ERP studies of the N170 typically demonstrate selectivity for words more strikingly over the left hemisphere. Why is right hemisphere selectivity for words during the N170 epoch typically not observed, despite the clear involvement of this region in word processing? One possibility is that amplitude differences measured on averaged ERPs in previous studies may have been obscured by variation in peak latency across trials. This study examined this possibility by using single-trial analysis. Results show that words evoked greater single-trial N170s than control stimuli in the right hemisphere. Additionally, we observed larger trial-to-trial variability on N170 peak latency for words as compared to control stimuli over the right hemisphere. Results demonstrate that, in contrast to much of the prior literature, the N170 can be selective to words over the right hemisphere. This discrepancy is explained in terms of variability in trial-to-trial peak latency for responses to words over the right hemisphere. © 2017 Society for Psychophysiological Research.

  6. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.

    Science.gov (United States)

    Delorme, Arnaud; Makeig, Scott

    2004-03-15

    We have developed a toolbox and graphic user interface, EEGLAB, running under the crossplatform MATLAB environment (The Mathworks, Inc.) for processing collections of single-trial and/or averaged EEG data of any number of channels. Available functions include EEG data, channel and event information importing, data visualization (scrolling, scalp map and dipole model plotting, plus multi-trial ERP-image plots), preprocessing (including artifact rejection, filtering, epoch selection, and averaging), independent component analysis (ICA) and time/frequency decompositions including channel and component cross-coherence supported by bootstrap statistical methods based on data resampling. EEGLAB functions are organized into three layers. Top-layer functions allow users to interact with the data through the graphic interface without needing to use MATLAB syntax. Menu options allow users to tune the behavior of EEGLAB to available memory. Middle-layer functions allow users to customize data processing using command history and interactive 'pop' functions. Experienced MATLAB users can use EEGLAB data structures and stand-alone signal processing functions to write custom and/or batch analysis scripts. Extensive function help and tutorial information are included. A 'plug-in' facility allows easy incorporation of new EEG modules into the main menu. EEGLAB is freely available (http://www.sccn.ucsd.edu/eeglab/) under the GNU public license for noncommercial use and open source development, together with sample data, user tutorial and extensive documentation.

  7. Single-Trial Inference on Visual Attention

    DEFF Research Database (Denmark)

    Dyrholm, Mads; Kyllingsbæk, Søren; Vangkilde, Signe Allerup

    2011-01-01

    In this paper we take a step towards single-trial behavioral modeling within a Theory of Visual Attention (TVA). In selective attention tasks, such as the Partial Report paradigm, the subject is asked to ignore distractors and only report stimuli that belong to the target class. Nothing about...... Report trial. This result retrodicts a latent attentional state of the subject using the observed response from that particular trial and thus differs from other predictions made with TVA which are based on expected values of observed variables. We show an example of the result in single-trial analysis...

  8. Using Matrix and Tensor Factorizations for the Single-Trial Analysis of Population Spike Trains.

    Directory of Open Access Journals (Sweden)

    Arno Onken

    2016-11-01

    Full Text Available Advances in neuronal recording techniques are leading to ever larger numbers of simultaneously monitored neurons. This poses the important analytical challenge of how to capture compactly all sensory information that neural population codes carry in their spatial dimension (differences in stimulus tuning across neurons at different locations, in their temporal dimension (temporal neural response variations, or in their combination (temporally coordinated neural population firing. Here we investigate the utility of tensor factorizations of population spike trains along space and time. These factorizations decompose a dataset of single-trial population spike trains into spatial firing patterns (combinations of neurons firing together, temporal firing patterns (temporal activation of these groups of neurons and trial-dependent activation coefficients (strength of recruitment of such neural patterns on each trial. We validated various factorization methods on simulated data and on populations of ganglion cells simultaneously recorded in the salamander retina. We found that single-trial tensor space-by-time decompositions provided low-dimensional data-robust representations of spike trains that capture efficiently both their spatial and temporal information about sensory stimuli. Tensor decompositions with orthogonality constraints were the most efficient in extracting sensory information, whereas non-negative tensor decompositions worked well even on non-independent and overlapping spike patterns, and retrieved informative firing patterns expressed by the same population in response to novel stimuli. Our method showed that populations of retinal ganglion cells carried information in their spike timing on the ten-milliseconds-scale about spatial details of natural images. This information could not be recovered from the spike counts of these cells. First-spike latencies carried the majority of information provided by the whole spike train about fine

  9. Neural Signatures of Rational and Heuristic Choice Strategies: A Single Trial ERP Analysis

    Directory of Open Access Journals (Sweden)

    Szymon Wichary

    2017-08-01

    Full Text Available In multi-attribute choice, people use heuristics to simplify decision problems. We studied the use of heuristic and rational strategies and their electrophysiological correlates. Since previous work linked the P3 ERP component to attention and decision making, we were interested whether the amplitude of this component is associated with decision strategy use. To this end, we recorded EEG when participants performed a two-alternative choice task, where they could acquire decision cues in a sequential manner and use them to make choices. We classified participants’ choices as consistent with a rational Weighted Additive rule (WADD or a simple heuristic Take The Best (TTB. Participants differed in their preference for WADD and TTB. Using a permutation-based single trial approach, we analyzed EEG responses to consecutive decision cues and their relation to the individual strategy preference. The preference for WADD over TTB was associated with overall higher signal amplitudes to decision cues in the P3 time window. Moreover, the preference for WADD was associated with similar P3 amplitudes to consecutive cues, whereas the preference for TTB was associated with substantial decreases in P3 amplitudes to consecutive cues. We also found that the preference for TTB was associated with enhanced N1 component to cues that discriminated decision alternatives, suggesting very early attention allocation to such cues by TTB users. Our results suggest that preference for either WADD or TTB has an early neural signature reflecting differences in attentional weighting of decision cues. In light of recent findings and hypotheses regarding P3, we interpret these results as indicating the involvement of catecholamine arousal systems in shaping predecisional information processing and strategy selection.

  10. Neural Signatures of Rational and Heuristic Choice Strategies: A Single Trial ERP Analysis.

    Science.gov (United States)

    Wichary, Szymon; Magnuski, Mikołaj; Oleksy, Tomasz; Brzezicka, Aneta

    2017-01-01

    In multi-attribute choice, people use heuristics to simplify decision problems. We studied the use of heuristic and rational strategies and their electrophysiological correlates. Since previous work linked the P3 ERP component to attention and decision making, we were interested whether the amplitude of this component is associated with decision strategy use. To this end, we recorded EEG when participants performed a two-alternative choice task, where they could acquire decision cues in a sequential manner and use them to make choices. We classified participants' choices as consistent with a rational Weighted Additive rule (WADD) or a simple heuristic Take The Best (TTB). Participants differed in their preference for WADD and TTB. Using a permutation-based single trial approach, we analyzed EEG responses to consecutive decision cues and their relation to the individual strategy preference. The preference for WADD over TTB was associated with overall higher signal amplitudes to decision cues in the P3 time window. Moreover, the preference for WADD was associated with similar P3 amplitudes to consecutive cues, whereas the preference for TTB was associated with substantial decreases in P3 amplitudes to consecutive cues. We also found that the preference for TTB was associated with enhanced N1 component to cues that discriminated decision alternatives, suggesting very early attention allocation to such cues by TTB users. Our results suggest that preference for either WADD or TTB has an early neural signature reflecting differences in attentional weighting of decision cues. In light of recent findings and hypotheses regarding P3, we interpret these results as indicating the involvement of catecholamine arousal systems in shaping predecisional information processing and strategy selection.

  11. Single-trial log transformation is optimal in frequency analysis of resting EEG alpha.

    Science.gov (United States)

    Smulders, Fren T Y; Ten Oever, Sanne; Donkers, Franc C L; Quaedflieg, Conny W E M; van de Ven, Vincent

    2018-02-01

    The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2 min of eyes-closed and 2 min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12 Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude. © 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. A single center analysis of factors influencing study start-up timeline in clinical trials.

    Science.gov (United States)

    Krafcik, Brianna M; Doros, Gheorghe; Malikova, Marina A

    2017-11-01

    Efficient start-up phase in clinical trials is crucial to execution. The goal was to determine factors contributing to delays. The start-up milestones were assessed for 38 studies and analyzed. Total start-up time was shorter for following studies: device trials, no outsourcing, fewer ancillary services used and in interventional versus observational designs. The use of a centralized Institutional Review Board (IRB) versus a local IRB reduced time to approval. Studies that never enrolled took longer on average to finalize their budget/contract, and obtain IRB than ones that did enroll. Different features of clinical trials can affect timeline of start-up process. An understanding of the impact of each feature allows for optimization.

  13. Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial.

    Science.gov (United States)

    Fiddelers, Audrey A A; van Montfoort, Aafke P A; Dirksen, Carmen D; Dumoulin, John C M; Land, Jolande A; Dunselman, Gerard A J; Janssen, J Marij; Severens, Johan L; Evers, Johannes L H

    2006-08-01

    Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.

  14. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis.

    Science.gov (United States)

    Marty, Francisco M; Ostrosky-Zeichner, Luis; Cornely, Oliver A; Mullane, Kathleen M; Perfect, John R; Thompson, George R; Alangaden, George J; Brown, Janice M; Fredricks, David N; Heinz, Werner J; Herbrecht, Raoul; Klimko, Nikolai; Klyasova, Galina; Maertens, Johan A; Melinkeri, Sameer R; Oren, Ilana; Pappas, Peter G; Ráčil, Zdeněk; Rahav, Galia; Santos, Rodrigo; Schwartz, Stefan; Vehreschild, J Janne; Young, Jo-Anne H; Chetchotisakd, Ploenchan; Jaruratanasirikul, Sutep; Kanj, Souha S; Engelhardt, Marc; Kaufhold, Achim; Ito, Masanori; Lee, Misun; Sasse, Carolyn; Maher, Rochelle M; Zeiher, Bernhardt; Vehreschild, Maria J G T

    2016-07-01

    Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response-ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)-according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19-179, range 2-882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33

  15. Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

    2017-03-01

    The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

  16. Trial Sequential Methods for Meta-Analysis

    Science.gov (United States)

    Kulinskaya, Elena; Wood, John

    2014-01-01

    Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

  17. No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

    Science.gov (United States)

    Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

    2017-09-01

    A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

  18. Combined versus single application of tranexamic acid in total knee and hip arthroplasty: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Peng Zhang, M M; Jifeng Li, M M; Xiao Wang, M M

    2017-07-01

    To compare the efficacy and safety of the combined application of both intravenous and topical tranexamic acid versus the single use of either application in patients with total knee and hip arthroplasty. Potentially relevant studies were identified from electronic databases including Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Patients undergoing primary total knee and hip arthroplasty were included in our studies, with an experimental group that received combined intravenous and topical application of tranexamic acid and a control group that received a single application of tranexamic acid or normal saline. The primary outcomes were total blood loss, hemoglobin decline and transfusion requirements. The secondary outcomes were length of stay, operation time and tranexamic acid-related adverse effects, such as superficial infection, deep vein thrombosis or pulmonary embolism. Modified Jadad scores were used to assess the quality of the included randomized controlled trials (RCTs). The data was pooled using RevMan 5.3. After testing for heterogeneity across studies, the data were aggregated using random-effects modeling when appropriate. We have registered the trial at http://www.researchregistry.com. Six RCTs that included 704 patients met the inclusion criteria. The present meta-analysis indicated significant differences existed in the total blood loss (MD = -134.65, 95% CI: -191.66 to -77.64, P tranexamic acid in total knee and hip arthroplasty was associated with significantly reduced total blood loss, postoperative hemoglobin decline, drainage volume, and transfusion requirements. Based on the limitations of current meta-analysis, well-designed, high-quality RCTs with long-term follow-up are still required. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  19. Clinical effectiveness of elective single versus double embryo transfer: meta-analysis of individual patient data from randomised trials

    NARCIS (Netherlands)

    McLernon, D. J.; Harrild, K.; Bergh, C.; Davies, M. J.; de Neubourg, D.; Dumoulin, J. C. M.; Gerris, J.; Kremer, J. A. M.; Martikainen, H.; Mol, B. W.; Norman, R. J.; Thurin-Kjellberg, A.; Tiitinen, A.; van Montfoort, A. P. A.; van Peperstraten, A. M.; van Royen, E.; Bhattacharya, S.

    2010-01-01

    Objective To compare the effectiveness of elective single embryo transfer versus double embryo transfer on the outcomes of live birth, multiple live birth, miscarriage, preterm birth, term singleton birth, and low birth weight after fresh embryo transfer, and on the outcomes of cumulative live birth

  20. Single-trial EEG-informed fMRI analysis of emotional decision problems in hot executive function.

    Science.gov (United States)

    Guo, Qian; Zhou, Tiantong; Li, Wenjie; Dong, Li; Wang, Suhong; Zou, Ling

    2017-07-01

    Executive function refers to conscious control in psychological process which relates to thinking and action. Emotional decision is a part of hot executive function and contains emotion and logic elements. As a kind of important social adaptation ability, more and more attention has been paid in recent years. Gambling task can be well performed in the study of emotional decision. As fMRI researches focused on gambling task show not completely consistent brain activation regions, this study adopted EEG-fMRI fusion technology to reveal brain neural activity related with feedback stimuli. In this study, an EEG-informed fMRI analysis was applied to process simultaneous EEG-fMRI data. First, relative power-spectrum analysis and K-means clustering method were performed separately to extract EEG-fMRI features. Then, Generalized linear models were structured using fMRI data and using different EEG features as regressors. The results showed that in the win versus loss stimuli, the activated regions almost covered the caudate, the ventral striatum (VS), the orbital frontal cortex (OFC), and the cingulate. Wide activation areas associated with reward and punishment were revealed by the EEG-fMRI integration analysis than the conventional fMRI results, such as the posterior cingulate and the OFC. The VS and the medial prefrontal cortex (mPFC) were found when EEG power features were performed as regressors of GLM compared with results entering the amplitudes of feedback-related negativity (FRN) as regressors. Furthermore, the brain region activation intensity was the strongest when theta-band power was used as a regressor compared with the other two fusion results. The EEG-based fMRI analysis can more accurately depict the whole-brain activation map and analyze emotional decision problems.

  1. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    Directory of Open Access Journals (Sweden)

    Xu L

    2016-07-01

    Full Text Available Liang Xu,1,2,* Xiaobo Wu,3,* Chun Hu,1,2 Zhiying Zhang,4 Le Zhang,1,2 Shujing Liang,1,2 Yingchun Xu,5 Fengchun Zhang1,2 1Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 2Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 3Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, 4Graduate School, Xuzhou Medical College, Xuzhou, 5Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015 comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS, and the secondary end points were the progression-free survival (PFS, overall response rate (ORR, and grade 3 or 4 toxicities. The pooled hazard ratio (HR and pooled risk ratio (RR were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002, PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001, and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001. Notably, subgroup analysis

  2. Clinical trials in dentistry in India: Analysis from trial registry.

    Science.gov (United States)

    Gowri, S; Kannan, Sridharan

    2017-01-01

    Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

  3. Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

    Science.gov (United States)

    Dutton, P; Love, S B; Billingham, L; Hassan, A B

    2018-05-01

    Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

  4. Single-center trials in neonatology: Issues to consider.

    Science.gov (United States)

    Sinha, Ian P; Sinha, Sunil K

    2015-12-01

    Single-center randomized controlled trials confer certain advantages over multi-center trials, in that they are cheaper and easier to design and conduct. However, recent research suggests that single-center trials are likely to overestimate treatment effects. There are notable examples in neonatology where results from multi-center trials have contradicted results of single-center studies. In this paper we discuss issues around external generalizability of single-center studies, and methodological issues that may cause bias. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

    2016-10-01

    The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of

  6. The Optimal Timing of Stage 2 Palliation for Hypoplastic Left Heart Syndrome: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set.

    Science.gov (United States)

    Meza, James M; Hickey, Edward J; Blackstone, Eugene H; Jaquiss, Robert D B; Anderson, Brett R; Williams, William G; Cai, Sally; Van Arsdell, Glen S; Karamlou, Tara; McCrindle, Brian W

    2017-10-31

    In infants requiring 3-stage single-ventricle palliation for hypoplastic left heart syndrome, attrition after the Norwood procedure remains significant. The effect of the timing of stage 2 palliation (S2P), a physician-modifiable factor, on long-term survival is not well understood. We hypothesized that an optimal interval between the Norwood and S2P that both minimizes pre-S2P attrition and maximizes post-S2P survival exists and is associated with individual patient characteristics. The National Institutes of Health/National Heart, Lung, and Blood Institute Pediatric Heart Network Single Ventricle Reconstruction Trial public data set was used. Transplant-free survival (TFS) was modeled from (1) Norwood to S2P and (2) S2P to 3 years by using parametric hazard analysis. Factors associated with death or heart transplantation were determined for each interval. To account for staged procedures, risk-adjusted, 3-year, post-Norwood TFS (the probability of TFS at 3 years given survival to S2P) was calculated using parametric conditional survival analysis. TFS from the Norwood to S2P was first predicted. TFS after S2P to 3 years was then predicted and adjusted for attrition before S2P by multiplying by the estimate of TFS to S2P. The optimal timing of S2P was determined by generating nomograms of risk-adjusted, 3-year, post-Norwood, TFS versus the interval from the Norwood to S2P. Of 547 included patients, 399 survived to S2P (73%). Of the survivors to S2P, 349 (87%) survived to 3-year follow-up. The median interval from the Norwood to S2P was 5.1 (interquartile range, 4.1-6.0) months. The risk-adjusted, 3-year, TFS was 68±7%. A Norwood-S2P interval of 3 to 6 months was associated with greatest 3-year TFS overall and in patients with few risk factors. In patients with multiple risk factors, TFS was severely compromised, regardless of the timing of S2P and most severely when S2P was performed early. No difference in the optimal timing of S2P existed when stratified by

  7. Single-trial event-related potentials to significant stimuli.

    Science.gov (United States)

    Rushby, Jacqueline A; Barry, Robert J

    2009-11-01

    The stimulus-response pattern of the skin conductance response (SCR) was used as a model of the Orienting Reflex (OR) to assess the P1, N1, P2, N2 and late positive complex (LPC/P300) components of the ERP in a simple habituation paradigm, in which a single series of 12 innocuous tones were presented at a very long interstimulus interval (2 min). To maintain their waking state during this boring task, participants were instructed to alternately close or open their eyes to each stimulus. None of the baseline-to-peak ERP measures showed trials effects comparable with the marked habituation over trials shown by the SCRs. Principal Components Analysis was used to decompose the ERP, yielding factors identified as the N1, N2, P3a, P3b and Novelty P3 components. An additional factor represented later eye-movement activity. No trial effects were apparent for the N1, N2, P3a or P3b components. The Novelty P3 showed marked response decrement over trials. These results are discussed in relation to current conceptualisations of the OR.

  8. Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

    Science.gov (United States)

    Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

    2017-05-01

    AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Single-stage laparoscopic common bile duct exploration and cholecystectomy versus two-stage endoscopic stone extraction followed by laparoscopic cholecystectomy for patients with gallbladder stones with common bile duct stones: systematic review and meta-analysis of randomized trials with trial sequential analysis.

    Science.gov (United States)

    Singh, Anand Narayan; Kilambi, Ragini

    2018-03-30

    The ideal management of common bile duct (CBD) stones associated with gall stones is a matter of debate. We planned a meta-analysis of randomized trials comparing single-stage laparoscopic CBD exploration and cholecystectomy (LCBDE) with two-stage preoperative endoscopic stone extraction followed by cholecystectomy (ERCP + LC). We searched the Pubmed/Medline, Web of science, Science citation index, Google scholar and Cochrane Central Register of Controlled trials electronic databases till June 2017 for all English language randomized trials comparing the two approaches. Statistical analysis was performed using Review Manager (RevMan) [Computer program], Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014 and results were expressed as odds ratio for dichotomous variables and mean difference for continuous. p value ≤ 0.05 was considered significant. Trial sequential analysis (TSA) was performed using TSA version 0.9.5.5 (Copenhagen: The Copenhagen Trial Unit, Centre for Clinical Intervention Research, 2016). PROSPERO trial registration number is CRD42017074673. A total of 11 trials were included in the analysis, with a total of 1513 patients (751-LCBDE; 762-ERCP + LC). LCBDE was found to have significantly lower rates of technical failure [OR 0.59, 95% CI (0.38, 0.93), p = 0.02] and shorter hospital stay [MD - 1.63, 95% CI (- 3.23, - 0.03), p = 0.05]. There was no significant difference in mortality [OR 0.37, 95% CI (0.09, 1.51), p = 0.17], morbidity [OR 0.97, 95% CI (0.70, 1.33), p = 0.84], cost [MD - 379.13, 95% CI (- 784.80, 111.2), p = 0.13] or recurrent/retained stones [OR 1.01, 95% CI (0.38, 2.73), p = 0.98]. TSA showed that although the Z-curve crossed the boundaries of conventional significance, the estimated information size is yet to be achieved. Single-stage LCBDE is superior to ERCP + LC in terms of technical success and shorter hospital stay in good-risk patients with

  10. Microfluidics for single cell analysis

    DEFF Research Database (Denmark)

    Jensen, Marie Pødenphant

    Isolation and manipulation of single cells have gained an increasing interest from researchers because of the heterogeneity of cells from the same cell culture. Single cell analysis can ensure a better understanding of differences between individual cells and potentially solve a variety of clinical...... problems. In this thesis lab on a chip systems for rare single cell analysis are investigated. The focus was to develop a commercial, disposable device for circulating tumour cell (CTC) analysis. Such a device must be able to separate rare cells from blood samples and subsequently capture the specific...... cells, and simultaneously be fabricated and operated at low costs and be user-friendly. These challenges were addressed through development of two microfluidic devices, one for rare cell isolation based on pinched flow fractionation (PFF) and one for single cell capture based on hydrodynamic trapping...

  11. Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

    Science.gov (United States)

    Hu, L; Zhang, Z G; Mouraux, A; Iannetti, G D

    2015-05-01

    Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical

  12. Post endodontic pain following single-visit root canal preparation with rotary vs reciprocating instruments: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Hou, Xiao-Mei; Su, Zheng; Hou, Ben-Xiang

    2017-05-25

    In endodontic therapy, continuous rotary instrumentation reduced debris compared to reciprocal instrumentation, which might affect the incidence of post-endodontic pain (PP). The aim of our study was to assess whether PP incidence and levels were influenced by the choice of rotary or reciprocal instruments. In this meta-analysis the Pubmed and EM databases were searched for prospective clinical randomized trials published before April 20, 2016, using combinations of the keywords: root canal preparation/instrumentation/treatment/therapy; post-operative/endodontic pain; reciprocal and rotary instruments. Three studies were included, involving a total of 1,317 patients, 659 treated with reciprocating instruments and 658 treated with rotary instruments. PP was reported in 139 patients in the reciprocating group and 172 in the rotary group. The PP incidence odds ratio was 1.27 with 95% confidence interval (CI) (0.25, 6.52) favoring rotary instruments. The mild, moderate and severe PP levels odds ratios were 0.31 (0.11, 0.84), 2.24 (0.66, 7.59) and 11.71 (0.63, 218.15), respectively. No evidence of publication bias was found. Rotary instrument choice in endodontic therapy is associated with a lower incidence of PP than reciprocating instruments, while reciprocating instruments are associated with less mild PP incidence.

  13. Single Cell Isolation and Analysis

    Directory of Open Access Journals (Sweden)

    Ping Hu

    2016-10-01

    Full Text Available Increasing evidence shows that the heterogeneity of individual cells within a genetically identical population can be critical to their peculiar function and fate. Conventional cell based assays mainly analysis the average responses from a population cells, while the difference within individual cells may often be masked. The cell size, RNA transcripts and protein expression level are quite different within individual cells and these variations are key point to answer the problems in cancer, neurobiology, stem cell biology, immunology and developmental biology. To better understand the cell-to-cell variations, the single cell analysis can provide much more detailed information which may be helpful for therapeutic decisions in an increasingly personalized medicine. In this review, we will focus on the recent development in single cell analysis, including methods used in single cell isolation, analysis and some application examples. The review provides the historical background to single cell analysis, discusses limitations, and current and future possibilities in this exciting field of research.

  14. Testing competing hypotheses about single trial fMRI

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Purushotham, Archana; Kim, Seong-Ge

    2002-01-01

    We use a Bayesian framework to compute probabilities of competing hypotheses about functional activation based on single trial fMRI measurements. Within the framework we obtain a complete probabilistic picture of competing hypotheses, hence control of both type I and type II errors....

  15. The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials.

    Science.gov (United States)

    Li, Guifang; Gao, Shunji; Sheng, Zhixin; Li, Bin

    2016-01-01

    To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients. © 2016 S. Karger AG, Basel.

  16. Two-year survival analysis of twisted wire fixed retainer versus spiral wire and fiber-reinforced composite retainers: a preliminary explorative single-blind randomized clinical trial.

    Science.gov (United States)

    Sobouti, Farhad; Rakhshan, Vahid; Saravi, Mahdi Gholamrezaei; Zamanian, Ali; Shariati, Mahsa

    2016-03-01

    Traditional retainers (both metal and fiber-reinforced composite [FRC]) have limitations, and a retainer made from more flexible ligature wires might be advantageous. We aimed to compare an experimental design with two traditional retainers. In this prospective preliminary clinical trial, 150 post-treatment patients were enrolled and randomly divided into three groups of 50 patients each to receive mandibular canine-to-canine retainers made of FRC, flexible spiral wire (FSW), and twisted wire (TW). The patients were monitored monthly. The time at which the first signs of breakage/debonding were detected was recorded. The success rates of the retainers were compared using chi-squared, Kaplan-Meier, and Cox proportional-hazard regression analyses (α = 0.05). In total, 42 patients in the FRC group, 41 in the FSW group, and 45 in the TW group completed the study. The 2-year failure rates were 35.7% in the FRC group, 26.8% in the FSW group, and 17.8% in the TW group. These rates differed insignificantly (chi-squared p = 0.167). According to the Kaplan-Meier analysis, failure occurred at 19.95 months in the FRC group, 21.37 months in the FSW group, and 22.36 months in the TW group. The differences between the survival rates in the three groups were not significant (Cox regression p = 0.146). Although the failure rate of the experimental retainer was two times lower than that of the FRC retainer, the difference was not statistically significant. The experimental TW retainer was successful, and larger studies are warranted to verify these results.

  17. Multi-port versus single-port cholecystectomy: results of a multi-centre, randomised controlled trial (MUSIC trial).

    Science.gov (United States)

    Arezzo, Alberto; Passera, Roberto; Bullano, Alberto; Mintz, Yoav; Kedar, Asaf; Boni, Luigi; Cassinotti, Elisa; Rosati, Riccardo; Fumagalli Romario, Uberto; Sorrentino, Mario; Brizzolari, Marco; Di Lorenzo, Nicola; Gaspari, Achille Lucio; Andreone, Dario; De Stefani, Elena; Navarra, Giuseppe; Lazzara, Salvatore; Degiuli, Maurizio; Shishin, Kirill; Khatkov, Igor; Kazakov, Ivan; Schrittwieser, Rudolf; Carus, Thomas; Corradi, Alessio; Sitzman, Guenther; Lacy, Antonio; Uranues, Selman; Szold, Amir; Morino, Mario

    2017-07-01

    Single-port laparoscopic surgery as an alternative to conventional laparoscopic cholecystectomy for benign disease has not yet been accepted as a standard procedure. The aim of the multi-port versus single-port cholecystectomy trial was to compare morbidity rates after single-access (SPC) and standard laparoscopy (MPC). This non-inferiority phase 3 trial was conducted at 20 hospital surgical departments in six countries. At each centre, patients were randomly assigned to undergo either SPC or MPC. The primary outcome was overall morbidity within 60 days after surgery. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov (NCT01104727). The study was conducted between April 2011 and May 2015. A total of 600 patients were randomly assigned to receive either SPC (n = 297) or MPC (n = 303) and were eligible for data analysis. Postsurgical complications within 60 days were recorded in 13 patients (4.7 %) in the SPC group and in 16 (6.1 %) in the MPC group (P = 0.468); however, single-access procedures took longer [70 min (range 25-265) vs. 55 min (range 22-185); P risk of incisional hernia following SPC do not appear to be justified. Patient satisfaction with aesthetic results was greater after SPC than after MPC.

  18. A comparative analysis of costs of single and dual rapid HIV and syphilis diagnostics: results from a randomised controlled trial in Colombia.

    Science.gov (United States)

    Obure, Carol Dayo; Gaitan-Duarte, Hernando; Losada Saenz, Ricardo; Gonzalez, Lina; Angel-Muller, Edith; Laverty, Maura; Perez, Freddy

    2017-11-01

    HIV and congenital syphilis are major public health burdens contributing to substantial perinatal morbidity and mortality globally. Although studies have reported on the costs and cost-effectiveness of rapid diagnostic tests (RDTs) for syphilis screening within antenatal care in a number of resource-constrained settings, empirical evidence on country-specific cost and estimates of single RDTs compared with dual RDTs for HIV and syphilis are limited. A cluster randomised controlled study design was used to compare the incremental costs of two testing algorithms: (1) single RDTs for HIV and syphilis and (2) dual RDTs for HIV and syphilis, in 12 health facilities in Bogota and Cali, Colombia. The costs of single HIV and syphilis RDTs and dual HIV and syphilis RDTs were collected from each of the health facilities. The economic costs per woman tested for HIV and syphilis and costs per woman treated for syphilis defined as the total costs required to test and treat one woman for syphilis were estimated. A total of 2214 women were tested in the study facilities. Cost per pregnant woman tested and cost per woman treated for syphilis were US$10.26 and US$607.99, respectively in the single RDT arm. For the dual RDTs, the cost per pregnant woman tested for HIV and syphilis and cost per woman treated for syphilis were US$15.89 and US$1859.26, respectively. Overall costs per woman tested for HIV and syphilis and cost per woman treated for syphilis were lower in Cali compared with Bogota across both intervention arms. Staff costs accounted for the largest proportion of costs while treatment costs comprised <1% of the preventive programme. Findings show lower average costs for single RDTs compared with dual RDTs with costs sensitive to personnel costs and the scale of output at the health facilities. NCT02454816; 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/.

  19. European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

    Science.gov (United States)

    Morant, Anne Vinther; Vestergaard, Henrik Tang

    2018-07-01

    A minimum of two positive, adequate, and well-controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case-by-case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  20. Power analysis of trials with multilevel data

    CERN Document Server

    Moerbeek, Mirjam

    2015-01-01

    Power Analysis of Trials with Multilevel Data covers using power and sample size calculations to design trials that involve nested data structures. The book gives a thorough overview of power analysis that details terminology and notation, outlines key concepts of statistical power and power analysis, and explains why they are necessary in trial design. It guides you in performing power calculations with hierarchical data, which enables more effective trial design.The authors are leading experts in the field who recognize that power analysis has attracted attention from applied statisticians i

  1. Analysis of Postural Control During Quiet Standing in a Population with Diabetic Peripheral Neuropathy Undergoing Moderate Intensity Aerobic Exercise Training: A Single Blind, Randomized Controlled Trial.

    Science.gov (United States)

    Dixit, Snehil; Maiya, Arun; Shastry, Barkur A; Guddattu, Vasudev

    2016-07-01

    The aim of this study was to investigate the effect of 8 wks of moderate-intensity aerobic exercise on postural control during quiet standing in type 2 diabetic peripheral neuropathy. Individuals were included in the study if they had type 2 diabetes with clinical neuropathy, defined by a minimum score of 7 on the Michigan Diabetic Neuropathy Score, following which the patients were randomly assigned to an 8-wk program by computer-generated random number tables to study or control group. Repeated-measures analysis of variance was used for data analysis (P < 0.05 was considered significant). After final randomization, there were 36 patients in the study group and 45 in the control group. On comparison of results for control and study groups using repeated-measures analysis of variance only in the eyes closed on foam condition was there was a significant difference between the two groups for sway velocity along the x-axis (df1, df2 = 1, 18, F = 3.86, P = 0.04) and mediolateral displacement (df1, df2 = 1, 18, F = 4.04, P = 0.03). Aerobic exercise training could exert a therapeutic effect on center of pressure movement only along the x-axis in the eyes closed condition on foam surface during quiet standing.

  2. Clinical trial data analysis using R

    National Research Council Canada - National Science Library

    Chen, Ding-Geng; Peace, Karl E

    2011-01-01

    .... Case studies demonstrate how to select the appropriate clinical trial data. The authors introduce the corresponding biostatistical analysis methods, followed by the step-by-step data analysis using R...

  3. SINGLE VERSUS MULTIPLE TRIAL VECTORS IN CLASSICAL DIFFERENTIAL EVOLUTION FOR OPTIMIZING THE QUANTIZATION TABLE IN JPEG BASELINE ALGORITHM

    Directory of Open Access Journals (Sweden)

    B Vinoth Kumar

    2017-07-01

    Full Text Available Quantization Table is responsible for compression / quality trade-off in baseline Joint Photographic Experts Group (JPEG algorithm and therefore it is viewed as an optimization problem. In the literature, it has been found that Classical Differential Evolution (CDE is a promising algorithm to generate the optimal quantization table. However, the searching capability of CDE could be limited due to generation of single trial vector in an iteration which in turn reduces the convergence speed. This paper studies the performance of CDE by employing multiple trial vectors in a single iteration. An extensive performance analysis has been made between CDE and CDE with multiple trial vectors in terms of Optimization process, accuracy, convergence speed and reliability. The analysis report reveals that CDE with multiple trial vectors improves the convergence speed of CDE and the same is confirmed using a statistical hypothesis test (t-test.

  4. Techniques for extracting single-trial activity patterns from large-scale neural recordings

    Science.gov (United States)

    Churchland, Mark M; Yu, Byron M; Sahani, Maneesh; Shenoy, Krishna V

    2008-01-01

    Summary Large, chronically-implanted arrays of microelectrodes are an increasingly common tool for recording from primate cortex, and can provide extracellular recordings from many (order of 100) neurons. While the desire for cortically-based motor prostheses has helped drive their development, such arrays also offer great potential to advance basic neuroscience research. Here we discuss the utility of array recording for the study of neural dynamics. Neural activity often has dynamics beyond that driven directly by the stimulus. While governed by those dynamics, neural responses may nevertheless unfold differently for nominally identical trials, rendering many traditional analysis methods ineffective. We review recent studies – some employing simultaneous recording, some not – indicating that such variability is indeed present both during movement generation, and during the preceding premotor computations. In such cases, large-scale simultaneous recordings have the potential to provide an unprecedented view of neural dynamics at the level of single trials. However, this enterprise will depend not only on techniques for simultaneous recording, but also on the use and further development of analysis techniques that can appropriately reduce the dimensionality of the data, and allow visualization of single-trial neural behavior. PMID:18093826

  5. Analysis of the PISC II trials results

    International Nuclear Information System (INIS)

    Haines, N.

    1988-01-01

    The paper presents the analysis scheme of the Programme for the Inspection of Steel Components PISC II trial results. The objective of the PISC II exercise is to evaluate the effectiveness of current and advanced NDT techniques for inspection of reactor pressure vessel components. The analysis scheme takes data from the Round Robin Trial (RRT) and Destructive Examination, then reduces it to a manageable form in order to present useful conclusions on the effectiveness of NDT. A description is given of the data provided by RRT, the data analysis scheme, the definition of analysis parameters, and the main methods of data presentation. (U.K.)

  6. Single-Level and Multilevel Mediation Analysis

    Science.gov (United States)

    Tofighi, Davood; Thoemmes, Felix

    2014-01-01

    Mediation analysis is a statistical approach used to examine how the effect of an independent variable on an outcome is transmitted through an intervening variable (mediator). In this article, we provide a gentle introduction to single-level and multilevel mediation analyses. Using single-level data, we demonstrate an application of structural…

  7. Single-trial detection of visual evoked potentials by common spatial patterns and wavelet filtering for brain-computer interface.

    Science.gov (United States)

    Tu, Yiheng; Huang, Gan; Hung, Yeung Sam; Hu, Li; Hu, Yong; Zhang, Zhiguo

    2013-01-01

    Event-related potentials (ERPs) are widely used in brain-computer interface (BCI) systems as input signals conveying a subject's intention. A fast and reliable single-trial ERP detection method can be used to develop a BCI system with both high speed and high accuracy. However, most of single-trial ERP detection methods are developed for offline EEG analysis and thus have a high computational complexity and need manual operations. Therefore, they are not applicable to practical BCI systems, which require a low-complexity and automatic ERP detection method. This work presents a joint spatial-time-frequency filter that combines common spatial patterns (CSP) and wavelet filtering (WF) for improving the signal-to-noise (SNR) of visual evoked potentials (VEP), which can lead to a single-trial ERP-based BCI.

  8. Decoding speech perception by native and non-native speakers using single-trial electrophysiological data.

    Directory of Open Access Journals (Sweden)

    Alex Brandmeyer

    Full Text Available Brain-computer interfaces (BCIs are systems that use real-time analysis of neuroimaging data to determine the mental state of their user for purposes such as providing neurofeedback. Here, we investigate the feasibility of a BCI based on speech perception. Multivariate pattern classification methods were applied to single-trial EEG data collected during speech perception by native and non-native speakers. Two principal questions were asked: 1 Can differences in the perceived categories of pairs of phonemes be decoded at the single-trial level? 2 Can these same categorical differences be decoded across participants, within or between native-language groups? Results indicated that classification performance progressively increased with respect to the categorical status (within, boundary or across of the stimulus contrast, and was also influenced by the native language of individual participants. Classifier performance showed strong relationships with traditional event-related potential measures and behavioral responses. The results of the cross-participant analysis indicated an overall increase in average classifier performance when trained on data from all participants (native and non-native. A second cross-participant classifier trained only on data from native speakers led to an overall improvement in performance for native speakers, but a reduction in performance for non-native speakers. We also found that the native language of a given participant could be decoded on the basis of EEG data with accuracy above 80%. These results indicate that electrophysiological responses underlying speech perception can be decoded at the single-trial level, and that decoding performance systematically reflects graded changes in the responses related to the phonological status of the stimuli. This approach could be used in extensions of the BCI paradigm to support perceptual learning during second language acquisition.

  9. Trial Sequential Analysis in systematic reviews with meta-analysis

    Directory of Open Access Journals (Sweden)

    Jørn Wetterslev

    2017-03-01

    Full Text Available Abstract Background Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors and too many false negative conclusions (type II errors. Methods We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. Results The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D2 measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in

  10. Parallel single-cell analysis microfluidic platform

    NARCIS (Netherlands)

    van den Brink, Floris Teunis Gerardus; Gool, Elmar; Frimat, Jean-Philippe; Bomer, Johan G.; van den Berg, Albert; le Gac, Severine

    2011-01-01

    We report a PDMS microfluidic platform for parallel single-cell analysis (PaSCAl) as a powerful tool to decipher the heterogeneity found in cell populations. Cells are trapped individually in dedicated pockets, and thereafter, a number of invasive or non-invasive analysis schemes are performed.

  11. A jackknife approach to quantifying single-trial correlation between covariance-based metrics undefined on a single-trial basis.

    Science.gov (United States)

    Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

    2015-07-01

    The quantification of covariance between neuronal activities (functional connectivity) requires the observation of correlated changes and therefore multiple observations. The strength of such neuronal correlations may itself undergo moment-by-moment fluctuations, which might e.g. lead to fluctuations in single-trial metrics such as reaction time (RT), or may co-fluctuate with the correlation between activity in other brain areas. Yet, quantifying the relation between moment-by-moment co-fluctuations in neuronal correlations is precluded by the fact that neuronal correlations are not defined per single observation. The proposed solution quantifies this relation by first calculating neuronal correlations for all leave-one-out subsamples (i.e. the jackknife replications of all observations) and then correlating these values. Because the correlation is calculated between jackknife replications, we address this approach as jackknife correlation (JC). First, we demonstrate the equivalence of JC to conventional correlation for simulated paired data that are defined per observation and therefore allow the calculation of conventional correlation. While the JC recovers the conventional correlation precisely, alternative approaches, like sorting-and-binning, result in detrimental effects of the analysis parameters. We then explore the case of relating two spectral correlation metrics, like coherence, that require multiple observation epochs, where the only viable alternative analysis approaches are based on some form of epoch subdivision, which results in reduced spectral resolution and poor spectral estimators. We show that JC outperforms these approaches, particularly for short epoch lengths, without sacrificing any spectral resolution. Finally, we note that the JC can be applied to relate fluctuations in any smooth metric that is not defined on single observations. Copyright © 2015. Published by Elsevier Inc.

  12. Applied Behavior Analysis: Beyond Discrete Trial Teaching

    Science.gov (United States)

    Steege, Mark W.; Mace, F. Charles; Perry, Lora; Longenecker, Harold

    2007-01-01

    We discuss the problem of autism-specific special education programs representing themselves as Applied Behavior Analysis (ABA) programs when the only ABA intervention employed is Discrete Trial Teaching (DTT), and often for limited portions of the school day. Although DTT has many advantages to recommend its use, it is not well suited to teach…

  13. Single-trial lie detection using a combined fNIRS-polygraph system

    Science.gov (United States)

    Bhutta, M. Raheel; Hong, Melissa J.; Kim, Yun-Hee; Hong, Keum-Shik

    2015-01-01

    Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes) for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS) is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into “true” and “lie” classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph. PMID:26082733

  14. Single-trial lie detection using a combined fNIRS-polygraph system

    Directory of Open Access Journals (Sweden)

    M. Raheel eBhutta

    2015-06-01

    Full Text Available Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into true and lie classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph.

  15. Single-trial regression elucidates the role of prefrontal theta oscillations in response conflict

    Directory of Open Access Journals (Sweden)

    Michael X Cohen

    2011-02-01

    Full Text Available In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does not in any given trial, whereas some evidence and intuition suggests that conflict may vary in intensity from trial to trial. Here we demonstrate that single-trial multiple regression of time-frequency electrophysiological activity reveals neural mechanisms of cognitive control that are not apparent in cross-trial averages. We also introduce a novel extension to oscillation phase coherence and synchronization analyses, based on weighted phase modulation, that has advantages over standard coherence measures in terms of linking electrophysiological dynamics to trial-varying behavior and experimental variables. After replicating previous response conflict findings using trial-averaged data, we extend these findings using single trial analytic methods to provide novel evidence for the role of medial frontal-lateral prefrontal theta-band synchronization in conflict-induced response time dynamics, including a role for lateral prefrontal theta-band activity in biasing response times according to perceptual conflict. Given that these methods shed new light on the prefrontal mechanisms of response conflict, they are also likely to be useful for investigating other neurocognitive processes.

  16. New frontiers in single-cell analysis

    OpenAIRE

    Templer, Richard H.; Ces, Oscar

    2008-01-01

    For this special issue of J. R. Soc. Interface we present an overview of the driving forces behind technological advances in the field of single-cell analysis. These range from increasing our understanding of cellular heterogeneity through to the study of rare cells, areas of research that cannot be tackled effectively using current high-throughput population-based averaging techniques.

  17. Single Trial Probability Applications: Can Subjectivity Evade Frequency Limitations?

    Directory of Open Access Journals (Sweden)

    David Howden

    2009-10-01

    Full Text Available Frequency probability theorists define an event’s probability distribution as the limit of a repeated set of trials belonging to a homogeneous collective. The subsets of this collective are events which we have deficient knowledge about on an individual level, although for the larger collective we have knowledge its aggregate behavior. Hence, probabilities can only be achieved through repeated trials of these subsets arriving at the established frequencies that define the probabilities. Crovelli (2009 argues that this is a mistaken approach, and that a subjective assessment of individual trials should be used instead. Bifurcating between the two concepts of risk and uncertainty, Crovelli first asserts that probability is the tool used to manage uncertain situations, and then attempts to rebuild a definition of probability theory with this in mind. We show that such an attempt has little to gain, and results in an indeterminate application of entrepreneurial forecasting to uncertain decisions—a process far-removed from any application of probability theory.

  18. Research design considerations for single-dose analgesic clinical trials in acute pain

    DEFF Research Database (Denmark)

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C

    2016-01-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials......, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay...... sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable...

  19. Single cell elemental analysis using nuclear microscopy

    International Nuclear Information System (INIS)

    Ren, M.Q.; Thong, P.S.P.; Kara, U.; Watt, F.

    1999-01-01

    The use of Particle Induced X-ray Emission (PIXE), Rutherford Backscattering Spectrometry (RBS) and Scanning Transmission Ion Microscopy (STIM) to provide quantitative elemental analysis of single cells is an area which has high potential, particularly when the trace elements such as Ca, Fe, Zn and Cu can be monitored. We describe the methodology of sample preparation for two cell types, the procedures of cell imaging using STIM, and the quantitative elemental analysis of single cells using RBS and PIXE. Recent work on single cells at the Nuclear Microscopy Research Centre,National University of Singapore has centred around two research areas: (a) Apoptosis (programmed cell death), which has been recently implicated in a wide range of pathological conditions such as cancer, Parkinson's disease etc, and (b) Malaria (infection of red blood cells by the malaria parasite). Firstly we present results on the elemental analysis of human Chang liver cells (ATTCC CCL 13) where vanadium ions were used to trigger apoptosis, and demonstrate that nuclear microscopy has the capability of monitoring vanadium loading within individual cells. Secondly we present the results of elemental changes taking place in individual mouse red blood cells which have been infected with the malaria parasite and treated with the anti-malaria drug Qinghaosu (QHS)

  20. Meta-analysis in clinical trials revisited.

    Science.gov (United States)

    DerSimonian, Rebecca; Laird, Nan

    2015-11-01

    In this paper, we revisit a 1986 article we published in this Journal, Meta-Analysis in Clinical Trials, where we introduced a random-effects model to summarize the evidence about treatment efficacy from a number of related clinical trials. Because of its simplicity and ease of implementation, our approach has been widely used (with more than 12,000 citations to date) and the "DerSimonian and Laird method" is now often referred to as the 'standard approach' or a 'popular' method for meta-analysis in medical and clinical research. The method is especially useful for providing an overall effect estimate and for characterizing the heterogeneity of effects across a series of studies. Here, we review the background that led to the original 1986 article, briefly describe the random-effects approach for meta-analysis, explore its use in various settings and trends over time and recommend a refinement to the method using a robust variance estimator for testing overall effect. We conclude with a discussion of repurposing the method for Big Data meta-analysis and Genome Wide Association Studies for studying the importance of genetic variants in complex diseases. Published by Elsevier Inc.

  1. Citation Sentiment Analysis in Clinical Trial Papers.

    Science.gov (United States)

    Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua

    2015-01-01

    In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain.

  2. Combining features from ERP components in single-trial EEG for discriminating four-category visual objects

    Science.gov (United States)

    Wang, Changming; Xiong, Shi; Hu, Xiaoping; Yao, Li; Zhang, Jiacai

    2012-10-01

    Categorization of images containing visual objects can be successfully recognized using single-trial electroencephalograph (EEG) measured when subjects view images. Previous studies have shown that task-related information contained in event-related potential (ERP) components could discriminate two or three categories of object images. In this study, we investigated whether four categories of objects (human faces, buildings, cats and cars) could be mutually discriminated using single-trial EEG data. Here, the EEG waveforms acquired while subjects were viewing four categories of object images were segmented into several ERP components (P1, N1, P2a and P2b), and then Fisher linear discriminant analysis (Fisher-LDA) was used to classify EEG features extracted from ERP components. Firstly, we compared the classification results using features from single ERP components, and identified that the N1 component achieved the highest classification accuracies. Secondly, we discriminated four categories of objects using combining features from multiple ERP components, and showed that combination of ERP components improved four-category classification accuracies by utilizing the complementarity of discriminative information in ERP components. These findings confirmed that four categories of object images could be discriminated with single-trial EEG and could direct us to select effective EEG features for classifying visual objects.

  3. Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

    Science.gov (United States)

    Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

    1993-01-01

    The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

  4. Preliminary ten year results from a randomised single centre mass screening trial for abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Juul, Søren; Fasting, H

    2006-01-01

    At present, several regions and countries are considering screening for abdominal aortic aneurysm (AAA). However, The Chichester Aneurysms Screening Trial has reported poor long term benefit of screening for AAA. We therefore supplement previously published data with a preliminary analysis...

  5. Single-Trial Evoked Potential Estimating Based on Sparse Coding under Impulsive Noise Environment

    Directory of Open Access Journals (Sweden)

    Nannan Yu

    2018-01-01

    Full Text Available Estimating single-trial evoked potentials (EPs corrupted by the spontaneous electroencephalogram (EEG can be regarded as signal denoising problem. Sparse coding has significant success in signal denoising and EPs have been proven to have strong sparsity over an appropriate dictionary. In sparse coding, the noise generally is considered to be a Gaussian random process. However, some studies have shown that the background noise in EPs may present an impulsive characteristic which is far from Gaussian but suitable to be modeled by the α-stable distribution 1<α≤2. Consequently, the performances of general sparse coding will degrade or even fail. In view of this, we present a new sparse coding algorithm using p-norm optimization in single-trial EPs estimating. The algorithm can track the underlying EPs corrupted by α-stable distribution noise, trial-by-trial, without the need to estimate the α value. Simulations and experiments on human visual evoked potentials and event-related potentials are carried out to examine the performance of the proposed approach. Experimental results show that the proposed method is effective in estimating single-trial EPs under impulsive noise environment.

  6. Rating the methodological quality of single-subject designs and n-of-1 trials: introducing the Single-Case Experimental Design (SCED) Scale.

    Science.gov (United States)

    Tate, Robyn L; McDonald, Skye; Perdices, Michael; Togher, Leanne; Schultz, Regina; Savage, Sharon

    2008-08-01

    Rating scales that assess methodological quality of clinical trials provide a means to critically appraise the literature. Scales are currently available to rate randomised and non-randomised controlled trials, but there are none that assess single-subject designs. The Single-Case Experimental Design (SCED) Scale was developed for this purpose and evaluated for reliability. Six clinical researchers who were trained and experienced in rating methodological quality of clinical trials developed the scale and participated in reliability studies. The SCED Scale is an 11-item rating scale for single-subject designs, of which 10 items are used to assess methodological quality and use of statistical analysis. The scale was developed and refined over a 3-year period. Content validity was addressed by identifying items to reduce the main sources of bias in single-case methodology as stipulated by authorities in the field, which were empirically tested against 85 published reports. Inter-rater reliability was assessed using a random sample of 20/312 single-subject reports archived in the Psychological Database of Brain Impairment Treatment Efficacy (PsycBITE). Inter-rater reliability for the total score was excellent, both for individual raters (overall ICC = 0.84; 95% confidence interval 0.73-0.92) and for consensus ratings between pairs of raters (overall ICC = 0.88; 95% confidence interval 0.78-0.95). Item reliability was fair to excellent for consensus ratings between pairs of raters (range k = 0.48 to 1.00). The results were replicated with two independent novice raters who were trained in the use of the scale (ICC = 0.88, 95% confidence interval 0.73-0.95). The SCED Scale thus provides a brief and valid evaluation of methodological quality of single-subject designs, with the total score demonstrating excellent inter-rater reliability using both individual and consensus ratings. Items from the scale can also be used as a checklist in the design, reporting and critical

  7. Detection of User Independent Single Trial ERPs in Brain Computer Interfaces: An Adaptive Spatial Filtering Approach

    DEFF Research Database (Denmark)

    Leza, Cristina; Puthusserypady, Sadasivan

    2017-01-01

    Brain Computer Interfaces (BCIs) use brain signals to communicate with the external world. The main challenges to address are speed, accuracy and adaptability. Here, a novel algorithm for P300 based BCI spelling system is presented, specifically suited for single-trial detection of Event...

  8. Kernel PLS Estimation of Single-trial Event-related Potentials

    Science.gov (United States)

    Rosipal, Roman; Trejo, Leonard J.

    2004-01-01

    Nonlinear kernel partial least squaes (KPLS) regressior, is a novel smoothing approach to nonparametric regression curve fitting. We have developed a KPLS approach to the estimation of single-trial event related potentials (ERPs). For improved accuracy of estimation, we also developed a local KPLS method for situations in which there exists prior knowledge about the approximate latency of individual ERP components. To assess the utility of the KPLS approach, we compared non-local KPLS and local KPLS smoothing with other nonparametric signal processing and smoothing methods. In particular, we examined wavelet denoising, smoothing splines, and localized smoothing splines. We applied these methods to the estimation of simulated mixtures of human ERPs and ongoing electroencephalogram (EEG) activity using a dipole simulator (BESA). In this scenario we considered ongoing EEG to represent spatially and temporally correlated noise added to the ERPs. This simulation provided a reasonable but simplified model of real-world ERP measurements. For estimation of the simulated single-trial ERPs, local KPLS provided a level of accuracy that was comparable with or better than the other methods. We also applied the local KPLS method to the estimation of human ERPs recorded in an experiment on co,onitive fatigue. For these data, the local KPLS method provided a clear improvement in visualization of single-trial ERPs as well as their averages. The local KPLS method may serve as a new alternative to the estimation of single-trial ERPs and improvement of ERP averages.

  9. Unilateral pallidotomy in Parkinson's disease : a randomised, single-blind, multicentre trial

    NARCIS (Netherlands)

    de Bie, RMA; de Haan, RJ; Nijssen, PCG; Rutgers, AWF; Beute, GN; Haaxma, R; Schmand, B; Staal, MJ; Speelman, J.D.

    1999-01-01

    Background The results of several cohort studies suggest that patients with advanced Parkinson's disease would benefit from unilateral pallidotomy. We have assessed the efficacy of unilateral pallidotomy in a randomised, single-blind, multicentre trial. Methods We enrolled 37 patients with advanced

  10. Trial Sequential Analysis in systematic reviews with meta-analysis

    DEFF Research Database (Denmark)

    Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

    2017-01-01

    BACKGROUND: Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size...... from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated...

  11. LCA single score analysis of man-made cellulose fibres

    NARCIS (Netherlands)

    Shen, L.; Patel, M.K.

    2010-01-01

    In this study, the LCA report “Life Cycle assessment of man-made cellulose fibres” [3] is extended to the single score analysis in order to provide an additional basis for decision making. The single score analysis covers 9 to 11 environmental impact categories. Three single score methods (Single

  12. Clinical trials in neurology: design, conduct, analysis

    National Research Council Canada - National Science Library

    Ravina, Bernard

    2012-01-01

    .... Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases...

  13. Decoding sequence learning from single-trial intracranial EEG in humans.

    Directory of Open Access Journals (Sweden)

    Marzia De Lucia

    Full Text Available We propose and validate a multivariate classification algorithm for characterizing changes in human intracranial electroencephalographic data (iEEG after learning motor sequences. The algorithm is based on a Hidden Markov Model (HMM that captures spatio-temporal properties of the iEEG at the level of single trials. Continuous intracranial iEEG was acquired during two sessions (one before and one after a night of sleep in two patients with depth electrodes implanted in several brain areas. They performed a visuomotor sequence (serial reaction time task, SRTT using the fingers of their non-dominant hand. Our results show that the decoding algorithm correctly classified single iEEG trials from the trained sequence as belonging to either the initial training phase (day 1, before sleep or a later consolidated phase (day 2, after sleep, whereas it failed to do so for trials belonging to a control condition (pseudo-random sequence. Accurate single-trial classification was achieved by taking advantage of the distributed pattern of neural activity. However, across all the contacts the hippocampus contributed most significantly to the classification accuracy for both patients, and one fronto-striatal contact for one patient. Together, these human intracranial findings demonstrate that a multivariate decoding approach can detect learning-related changes at the level of single-trial iEEG. Because it allows an unbiased identification of brain sites contributing to a behavioral effect (or experimental condition at the level of single subject, this approach could be usefully applied to assess the neural correlates of other complex cognitive functions in patients implanted with multiple electrodes.

  14. Quantitative evaluation of muscle synergy models: a single-trial task decoding approach.

    Science.gov (United States)

    Delis, Ioannis; Berret, Bastien; Pozzo, Thierry; Panzeri, Stefano

    2013-01-01

    Muscle synergies, i.e., invariant coordinated activations of groups of muscles, have been proposed as building blocks that the central nervous system (CNS) uses to construct the patterns of muscle activity utilized for executing movements. Several efficient dimensionality reduction algorithms that extract putative synergies from electromyographic (EMG) signals have been developed. Typically, the quality of synergy decompositions is assessed by computing the Variance Accounted For (VAF). Yet, little is known about the extent to which the combination of those synergies encodes task-discriminating variations of muscle activity in individual trials. To address this question, here we conceive and develop a novel computational framework to evaluate muscle synergy decompositions in task space. Unlike previous methods considering the total variance of muscle patterns (VAF based metrics), our approach focuses on variance discriminating execution of different tasks. The procedure is based on single-trial task decoding from muscle synergy activation features. The task decoding based metric evaluates quantitatively the mapping between synergy recruitment and task identification and automatically determines the minimal number of synergies that captures all the task-discriminating variability in the synergy activations. In this paper, we first validate the method on plausibly simulated EMG datasets. We then show that it can be applied to different types of muscle synergy decomposition and illustrate its applicability to real data by using it for the analysis of EMG recordings during an arm pointing task. We find that time-varying and synchronous synergies with similar number of parameters are equally efficient in task decoding, suggesting that in this experimental paradigm they are equally valid representations of muscle synergies. Overall, these findings stress the effectiveness of the decoding metric in systematically assessing muscle synergy decompositions in task space.

  15. A MISO-ARX-Based Method for Single-Trial Evoked Potential Extraction

    Directory of Open Access Journals (Sweden)

    Nannan Yu

    2017-01-01

    Full Text Available In this paper, we propose a novel method for solving the single-trial evoked potential (EP estimation problem. In this method, the single-trial EP is considered as a complex containing many components, which may originate from different functional brain sites; these components can be distinguished according to their respective latencies and amplitudes and are extracted simultaneously by multiple-input single-output autoregressive modeling with exogenous input (MISO-ARX. The extraction process is performed in three stages: first, we use a reference EP as a template and decompose it into a set of components, which serve as subtemplates for the remaining steps. Then, a dictionary is constructed with these subtemplates, and EPs are preliminarily extracted by sparse coding in order to roughly estimate the latency of each component. Finally, the single-trial measurement is parametrically modeled by MISO-ARX while characterizing spontaneous electroencephalographic activity as an autoregression model driven by white noise and with each component of the EP modeled by autoregressive-moving-average filtering of the subtemplates. Once optimized, all components of the EP can be extracted. Compared with ARX, our method has greater tracking capabilities of specific components of the EP complex as each component is modeled individually in MISO-ARX. We provide exhaustive experimental results to show the effectiveness and feasibility of our method.

  16. Need for Outcome Scenario Analysis of Clinical Trials in Diabetes.

    Science.gov (United States)

    Garcia-Verdugo, Rosa; Erbach, Michael; Schnell, Oliver

    2017-03-01

    Since the FDA requirement for cardiovascular safety of all new antihyperglycemic drugs to enter the market, the number and extent of phase 3 clinical trials has markedly increased. Unexpected trial results imply an enormous economic, personal and time cost and has deleterious effects over R&D. To prevent unforeseen developments in clinical trials, we recommend performing a comprehensive prospective outcome scenario analysis before launching the trial. In this commentary, we discuss the most important factors to take in consideration for prediction of clinical trial outcome scenarios and propose a theoretical model for decision making.

  17. Micro-PIXE for single cell analysis

    International Nuclear Information System (INIS)

    Ortega, Richard

    2012-01-01

    The knowledge of the intracellular distribution of biological relevant metals is important to understand their mechanisms of action in cells, either for physiological, toxicological or pathological processes. However, the direct detection of trace metals in single cells is a challenging task that requires sophisticated analytical developments. The combination of micro-PIXE with RBS and STIM (Scanning Transmission Ion Microscopy) allows the quantitative determination of trace metal content within sub-cellular compartments. The application of STIM analysis provides high spatial resolution imaging (< 200 nm) and excellent mass sensitivity (< 0.1 ng). Application of the STIM-PIXE-RBS methodology is absolutely needed when organic mass loss appears during PIXE-RBS irradiation. This combination of STIM-PIXE-RBS provides fully quantitative determination of trace element content, expressed in μg/g, which is a quite unique capability for micro-PIXE compared to other micro-analytical methods such as the electron and synchrotron x-ray fluorescence. Examples of micro-PIXE studies for sub-cellular imaging of trace elements in various fields of interest will be presented: in patho-physiology of trace elements involved in neurodegenerative diseases such as Parkinson's disease, and in toxicology of metals such as cobalt. (author)

  18. Automated single-trial assessment of laser-evoked potentials as an objective functional diagnostic tool for the nociceptive system.

    Science.gov (United States)

    Hatem, S M; Hu, L; Ragé, M; Gierasimowicz, A; Plaghki, L; Bouhassira, D; Attal, N; Iannetti, G D; Mouraux, A

    2012-12-01

    To assess the clinical usefulness of an automated analysis of event-related potentials (ERPs). Nociceptive laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) were recorded in 37 patients with syringomyelia and 21 controls. LEP and SEP peak amplitudes and latencies were estimated using a single-trial automated approach based on time-frequency wavelet filtering and multiple linear regression, as well as a conventional approach based on visual inspection. The amplitudes and latencies of normal and abnormal LEP and SEP peaks were identified reliably using both approaches, with similar sensitivity and specificity. Because the automated approach provided an unbiased solution to account for average waveforms where no ERP could be identified visually, it revealed significant differences between patients and controls that were not revealed using the visual approach. The automated analysis of ERPs characterized reliably and objectively LEP and SEP waveforms in patients. The automated single-trial analysis can be used to characterize normal and abnormal ERPs with a similar sensitivity and specificity as visual inspection. While this does not justify its use in a routine clinical setting, the technique could be useful to avoid observer-dependent biases in clinical research. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Feasibility, Process, and Outcomes of Cardiovascular Clinical Trial Data Sharing: A Reproduction Analysis of the SMART-AF Trial.

    Science.gov (United States)

    Gay, Hawkins C; Baldridge, Abigail S; Huffman, Mark D

    2017-12-01

    Data sharing is as an expanding initiative for enhancing trust in the clinical research enterprise. To evaluate the feasibility, process, and outcomes of a reproduction analysis of the THERMOCOOL SMARTTOUCH Catheter for the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (SMART-AF) trial using shared clinical trial data. A reproduction analysis of the SMART-AF trial was performed using the data sets, data dictionary, case report file, and statistical analysis plan from the original trial accessed through the Yale Open Data Access Project using the SAS Clinical Trials Data Transparency platform. SMART-AF was a multicenter, single-arm trial evaluating the effectiveness and safety of an irrigated, contact force-sensing catheter for ablation of drug refractory, symptomatic paroxysmal atrial fibrillation in 172 participants recruited from 21 sites between June 2011 and December 2011. Analysis of the data was conducted between December 2016 and April 2017. Effectiveness outcomes included freedom from atrial arrhythmias after ablation and proportion of participants without any arrhythmia recurrence over the 12 months of follow-up after a 3-month blanking period. Safety outcomes included major adverse device- or procedure-related events. The SMART AF trial participants' mean age was 58.7 (10.8) years, and 72% were men. The time from initial proposal submission to final analysis was 11 months. Freedom from atrial arrhythmias at 12 months postprocedure was similar compared with the primary study report (74.0%; 95% CI, 66.0-82.0 vs 76.4%; 95% CI, 68.7-84.1). The reproduction analysis success rate was higher than the primary study report (65.8%; 95% CI 56.5-74.2 vs 75.6%; 95% CI, 67.2-82.5). Adverse events were minimal and similar between the 2 analyses, but contact force range or regression models could not be reproduced. The feasibility of a reproduction analysis of the SMART-AF trial was demonstrated through an academic data-sharing platform. Data sharing can be

  20. An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

    Science.gov (United States)

    Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

    2013-11-01

    To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

  1. Robust inference from multiple test statistics via permutations: a better alternative to the single test statistic approach for randomized trials.

    Science.gov (United States)

    Ganju, Jitendra; Yu, Xinxin; Ma, Guoguang Julie

    2013-01-01

    Formal inference in randomized clinical trials is based on controlling the type I error rate associated with a single pre-specified statistic. The deficiency of using just one method of analysis is that it depends on assumptions that may not be met. For robust inference, we propose pre-specifying multiple test statistics and relying on the minimum p-value for testing the null hypothesis of no treatment effect. The null hypothesis associated with the various test statistics is that the treatment groups are indistinguishable. The critical value for hypothesis testing comes from permutation distributions. Rejection of the null hypothesis when the smallest p-value is less than the critical value controls the type I error rate at its designated value. Even if one of the candidate test statistics has low power, the adverse effect on the power of the minimum p-value statistic is not much. Its use is illustrated with examples. We conclude that it is better to rely on the minimum p-value rather than a single statistic particularly when that single statistic is the logrank test, because of the cost and complexity of many survival trials. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Applicability of supervised discriminant analysis models to analyze astigmatism clinical trial data.

    Science.gov (United States)

    Sedghipour, Mohammad Reza; Sadeghi-Bazargani, Homayoun

    2012-01-01

    In astigmatism clinical trials where more complex measurements are common, especially in nonrandomized small sized clinical trials, there is a demand for the development and application of newer statistical methods. The source data belonged to a project on astigmatism treatment. Data were used regarding a total of 296 eyes undergoing different astigmatism treatment modalities: wavefront-guided photorefractive keratectomy, cross-cylinder photorefractive keratectomy, and monotoric (single) photorefractive keratectomy. Astigmatism analysis was primarily done using the Alpins method. Prior to fitting partial least squares regression discriminant analysis, a preliminary principal component analysis was done for data overview. Through fitting the partial least squares regression discriminant analysis statistical method, various model validity and predictability measures were assessed. The model found the patients treated by the wavefront method to be different from the two other treatments both in baseline and outcome measures. Also, the model found that patients treated with the cross-cylinder method versus the single method didn't appear to be different from each other. This analysis provided an opportunity to compare the three methods while including a substantial number of baseline and outcome variables. Partial least squares regression discriminant analysis had applicability for the statistical analysis of astigmatism clinical trials and it may be used as an adjunct or alternative analysis method in small sized clinical trials.

  3. A Coorientational Analysis of Trial Lawyer and News Reporter Relationships.

    Science.gov (United States)

    Lipschultz, Jeremy Harris

    A study considered the relationships of trial lawyers and news reporters, using the coorientation measurement model and Q-methodology, and adapting an analysis of variance experimental design. Sixty statements were constructed and administered to 24 subjects (12 trial lawyers and 12 news reporters) in two large midwestern cities. It was found…

  4. Survival following ruptured abdominal aortic aneurysm before and during the IMPROVE Trial: a single-centre series.

    Science.gov (United States)

    Ambler, G K; Twine, C P; Shak, J; Rollins, K E; Varty, K; Coughlin, P A; Hayes, P D; Boyle, J R

    2014-04-01

    The first large-scale randomised trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair [IMPROVE]) for endovascular repair of ruptured abdominal aortic aneurysm (rEVAR) has recently finished recruiting patients. The aim of this study was to examine the impact on survival after rEVAR when the IMPROVE protocol was initiated in a high volume abdominal aortic aneurysm (AAA) centre previously performing rEVAR. One hundred and sixty-nine patients requiring emergency infrarenal AAA repair from January 2006 to April 2013 were included. Eighty-four patients were treated before (38 rEVAR, 46 open) and 85 (31 rEVAR, 54 open) were treated during the trial period. A retrospective analysis was performed. Before the trial, there was a significant survival benefit for rEVAR over open repair (90-day mortality 13% vs. 30%, p = .04, difference remained significant up to 2 years postoperatively). This survival benefit was lost after starting randomisation (90-day mortality 35% vs. 33%, p = .93). There was an increase in overall 30-day mortality from 15% to 31% (p = .02), while there was no change for open repair (p = .438). There was a significant decrease in general anaesthetic use (p = .002) for patients treated during the trial. Randomised patients had shorter hospital and intensive treatment unit stays (p = .006 and p = .03 respectively). The change in survival seen during the IMROVE trial highlights the need for randomised rather than cohort data to eliminate selection bias. These results from a single centre reinforce those recently reported in IMPROVE. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  5. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  6. Initial Single-Shell Tank Retrieval System mission analysis report

    International Nuclear Information System (INIS)

    Hertzel, J.S.

    1996-03-01

    This document provides the mission analysis for the Initial Single-Shell Tank Retrieval System task, which supports the Single-Shell Tank Waste Retrieval Program in its commitment to remove waste from single-shell tanks for treatment and final closure

  7. On assessing surrogacy in a single trial setting using a semi-competing risks paradigm

    Science.gov (United States)

    Ghosh, Debashis

    2009-01-01

    Summary There has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this paper, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semi-competing risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed by Buyse and Molenberghs (1998, Biometrics, 1014 – 1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study. PMID:18759839

  8. Single Molecule Analysis Research Tool (SMART: an integrated approach for analyzing single molecule data.

    Directory of Open Access Journals (Sweden)

    Max Greenfeld

    Full Text Available Single molecule studies have expanded rapidly over the past decade and have the ability to provide an unprecedented level of understanding of biological systems. A common challenge upon introduction of novel, data-rich approaches is the management, processing, and analysis of the complex data sets that are generated. We provide a standardized approach for analyzing these data in the freely available software package SMART: Single Molecule Analysis Research Tool. SMART provides a format for organizing and easily accessing single molecule data, a general hidden Markov modeling algorithm for fitting an array of possible models specified by the user, a standardized data structure and graphical user interfaces to streamline the analysis and visualization of data. This approach guides experimental design, facilitating acquisition of the maximal information from single molecule experiments. SMART also provides a standardized format to allow dissemination of single molecule data and transparency in the analysis of reported data.

  9. The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

    OpenAIRE

    Matusz, P.J.; Thelen, A.; Amrein, S.; Geiser, E.; Anken, J.; Murray, M.M.

    2015-01-01

    Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a ...

  10. Issues in data monitoring and interim analysis of trials.

    Science.gov (United States)

    Grant, A M; Altman, D G; Babiker, A B; Campbell, M K; Clemens, F J; Darbyshire, J H; Elbourne, D R; McLeer, S K; Parmar, M K B; Pocock, S J; Spiegelhalter, D J; Sydes, M R; Walker, A E; Wallace, S A

    2005-03-01

    included, although interaction with the DMCs of similar ongoing trials is controversial. A range of formal statistical approaches can be used, although this is only one of a number of considerations. DMCs usually reach decisions by consensus, but other approaches are sometimes used. The general, but not unanimous, view is that DMCs should be advisory rather than executive on the basis that it is the trial organisers who are ultimately responsible for the conduct of the trial. Some form of data monitoring should be considered for all RCTs, with reasons given where there is no DMC or when any member is not independent. An early DMC meeting is helpful, determining roles and responsibilities; planned operations can be agreed with investigators and sponsors/funders. A template for a DMC charter is suggested. Competing interests should be declared. DMC size (commonly three to eight people) is chosen to optimise performance. Members are usually independent and drawn from appropriate backgrounds, and some, particularly the chair, are experienced. A minimum frequency of meetings is usually agreed, with flexibility for more if needed. The DMC should understand and agree the statistical approach (and guidelines) chosen, with both the DMC statistician and analysis statistician competent to apply the method. A DMC's primary purpose is to ensure that continuing a trial according to its protocol is ethical, taking account of both individual and collective ethics. A broader remit in respect of wider ethical issues is controversial; arguably, these are primarily the responsibility of research ethics committees, trial steering committees and investigators. The DMC should know the range of recommendations or decisions open to it, in advance. A record should be kept describing the key issues discussed and the rationale for decisions taken. Errors are likely to be reduced if a DMC makes a thorough review of the evidence and has a clear understanding of how it should function, there is active

  11. Single-trial multisensory memories affect later auditory and visual object discrimination.

    Science.gov (United States)

    Thelen, Antonia; Talsma, Durk; Murray, Micah M

    2015-05-01

    Multisensory memory traces established via single-trial exposures can impact subsequent visual object recognition. This impact appears to depend on the meaningfulness of the initial multisensory pairing, implying that multisensory exposures establish distinct object representations that are accessible during later unisensory processing. Multisensory contexts may be particularly effective in influencing auditory discrimination, given the purportedly inferior recognition memory in this sensory modality. The possibility of this generalization and the equivalence of effects when memory discrimination was being performed in the visual vs. auditory modality were at the focus of this study. First, we demonstrate that visual object discrimination is affected by the context of prior multisensory encounters, replicating and extending previous findings by controlling for the probability of multisensory contexts during initial as well as repeated object presentations. Second, we provide the first evidence that single-trial multisensory memories impact subsequent auditory object discrimination. Auditory object discrimination was enhanced when initial presentations entailed semantically congruent multisensory pairs and was impaired after semantically incongruent multisensory encounters, compared to sounds that had been encountered only in a unisensory manner. Third, the impact of single-trial multisensory memories upon unisensory object discrimination was greater when the task was performed in the auditory vs. visual modality. Fourth, there was no evidence for correlation between effects of past multisensory experiences on visual and auditory processing, suggestive of largely independent object processing mechanisms between modalities. We discuss these findings in terms of the conceptual short term memory (CSTM) model and predictive coding. Our results suggest differential recruitment and modulation of conceptual memory networks according to the sensory task at hand. Copyright

  12. Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

    Science.gov (United States)

    Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

    2018-05-01

    Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

  13. Laparoendoscopic Single-Site Surgery for the Treatment of Benign Adnexal Disease: A Prospective Trial

    Directory of Open Access Journals (Sweden)

    Anna Fagotti

    2010-01-01

    Full Text Available Background. To validate feasibility, efficacy, and safeness of laparoscopic treatment of benign adnexal diseases through a single transumbilical access (LESS in a prospective series of patients. Methods. A prospective clinical trial including 30 women has been conducted at the Division of Gynecology of Catholic University of Sacred Hearth of Rome. Patients underwent different laparoscopic procedures by LESS utilizing a multiport trocar and conventional straight laparoscopic instrumentation. Intra and perioperative outcome has been reported. Results. Ten mono/bilateral adnexectomies and 20 cystectomies have been performed by LESS approach. Laparoscopic procedures were completed through a single access in 28 cases (93.4%. No major intra- or postoperative complications were observed. Mean hospital stay was 1.3 days. Conclusions. LESS approach is feasible to treat benign adnexal disease with a very low conversion rate and no early or late complications. More clinical data are needed to confirm these advantages compared to standard laparoscopic technique.

  14. Best practice for analysis of shared clinical trial data

    Directory of Open Access Journals (Sweden)

    Sally Hollis

    2016-07-01

    Full Text Available Abstract Background Greater transparency, including sharing of patient-level data for further research, is an increasingly important topic for organisations who sponsor, fund and conduct clinical trials. This is a major paradigm shift with the aim of maximising the value of patient-level data from clinical trials for the benefit of future patients and society. We consider the analysis of shared clinical trial data in three broad categories: (1 reanalysis - further investigation of the efficacy and safety of the randomized intervention, (2 meta-analysis, and (3 supplemental analysis for a research question that is not directly assessing the randomized intervention. Discussion In order to support appropriate interpretation and limit the risk of misleading findings, analysis of shared clinical trial data should have a pre-specified analysis plan. However, it is not generally possible to limit bias and control multiplicity to the extent that is possible in the original trial design, conduct and analysis, and this should be acknowledged and taken into account when interpreting results. We highlight a number of areas where specific considerations arise in planning, conducting, interpreting and reporting analyses of shared clinical trial data. A key issue is that that these analyses essentially share many of the limitations of any post hoc analyses beyond the original specified analyses. The use of individual patient data in meta-analysis can provide increased precision and reduce bias. Supplemental analyses are subject to many of the same issues that arise in broader epidemiological analyses. Specific discussion topics are addressed within each of these areas. Summary Increased provision of patient-level data from industry and academic-led clinical trials for secondary research can benefit future patients and society. Responsible data sharing, including transparency of the research objectives, analysis plans and of the results will support appropriate

  15. Effects of Helicobacter pylori treatment on rosacea: A single-arm clinical trial study.

    Science.gov (United States)

    Saleh, Parviz; Naghavi-Behzad, Mohammad; Herizchi, Hamdieh; Mokhtari, Fatemeh; Mirza-Aghazadeh-Attari, Mohammad; Piri, Reza

    2017-09-01

    Rosacea is a chronic dermatological disease. Helicobacter pylori has been discussed as one of its causative factors. In this clinical trial study, we attempted to evaluate the effect of H. pylori standard eradication protocol on the rosacea clinical course. In this single-arm clinical trial, patients ascertained to have H. pylori infection based on serological studies were assessed to examine existence of rosacea. Patients with concurrent rosacea and H. pylori infection were included in the study and underwent standard H. pylori eradication therapy. Rosacea was evaluated using the Duluth rosacea grading score at the beginning, 2 months later and at the end of the trial (day 180). Of 872 patients positive for H. pylori, 167 patients (19.15%) manifested the clinical features of rosacea. The patients with concurrent rosacea were younger (P < 0.001) and with a female sex predominance (P = 0.03) when compared with rosacea-free patients. Of 167 patients, 150 received H. pylori eradication therapy, demonstrating a 92% (138/150) cure rate. The rosacea Duluth score grading on day 0, 60 and 180 among 138 patients significantly decreased in most of the criteria except for telangiectasias (P = 0.712), phymatous changes (P = 0.535) and the existence of peripheral involvement (P = 0.431). The present study concluded that H. pylori eradication leads to improvement of rosacea. © 2017 Japanese Dermatological Association.

  16. Single-trial effective brain connectivity patterns enhance discriminability of mental imagery tasks

    Science.gov (United States)

    Rathee, Dheeraj; Cecotti, Hubert; Prasad, Girijesh

    2017-10-01

    Objective. The majority of the current approaches of connectivity based brain-computer interface (BCI) systems focus on distinguishing between different motor imagery (MI) tasks. Brain regions associated with MI are anatomically close to each other, hence these BCI systems suffer from low performances. Our objective is to introduce single-trial connectivity feature based BCI system for cognition imagery (CI) based tasks wherein the associated brain regions are located relatively far away as compared to those for MI. Approach. We implemented time-domain partial Granger causality (PGC) for the estimation of the connectivity features in a BCI setting. The proposed hypothesis has been verified with two publically available datasets involving MI and CI tasks. Main results. The results support the conclusion that connectivity based features can provide a better performance than a classical signal processing framework based on bandpass features coupled with spatial filtering for CI tasks, including word generation, subtraction, and spatial navigation. These results show for the first time that connectivity features can provide a reliable performance for imagery-based BCI system. Significance. We show that single-trial connectivity features for mixed imagery tasks (i.e. combination of CI and MI) can outperform the features obtained by current state-of-the-art method and hence can be successfully applied for BCI applications.

  17. Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

    Science.gov (United States)

    Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

    2015-02-01

    Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

  18. Single-Trial Event-Related Potential Based Rapid Image Triage System

    Directory of Open Access Journals (Sweden)

    Ke Yu

    2011-06-01

    Full Text Available Searching for points of interest (POI in large-volume imagery is a challenging problem with few good solutions. In this work, a neural engineering approach called rapid image triage (RIT which could offer about a ten-fold speed up in POI searching is developed. It is essentially a cortically-coupled computer vision technique, whereby the user is presented bursts of images at a speed of 6–15 images per second and then neural signals called event-related potential (ERP is used as the ‘cue’ for user seeing images of high relevance likelihood. Compared to past efforts, the implemented system has several unique features: (1 it applies overlapping frames in image chip preparation, to ensure rapid image triage performance; (2 a novel common spatial-temporal pattern (CSTP algorithm that makes use of both spatial and temporal patterns of ERP topography is proposed for high-accuracy single-trial ERP detection; (3 a weighted version of probabilistic support-vector-machine (SVM is used to address the inherent unbalanced nature of single-trial ERP detection for RIT. High accuracy, fast learning, and real-time capability of the developed system shown on 20 subjects demonstrate the feasibility of a brainmachine integrated rapid image triage system for fast detection of POI from large-volume imagery.

  19. Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial.

    Science.gov (United States)

    Enander, Jesper; Andersson, Erik; Mataix-Cols, David; Lichtenstein, Linn; Alström, Katarina; Andersson, Gerhard; Ljótsson, Brjánn; Rück, Christian

    2016-02-02

    To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. A 12 week single blind parallel group randomised controlled trial. Academic medical centre. 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD-YBOCS) score of ≥ 20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a ≥ 30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference -7.1 points, 95% confidence interval -9.8 to -4.4), depression (MADRS-S group difference -4.5 points, -7.5 to -1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self reported satisfaction was high. CBT can be delivered safely via the internet to patients with body

  20. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Krebs, Teri S; Johansen, Pål-Ørjan

    2012-07-01

    Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

  1. Meta-analysis of five photodisinfection clinical trials for periodontitis

    Science.gov (United States)

    Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

    2009-06-01

    Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.

  2. Validity and reliability of the single-trial line drill test of anaerobic power in basketball players.

    Science.gov (United States)

    Fatouros, I G; Laparidis, K; Kambas, A; Chatzinikolaou, A; Techlikidou, E; Katrabasas, I; Douroudos, I; Leontsini, D; Berberidou, F; Draganidis, D; Christoforidis, C; Tsoukas, D; Kelis, S; Taxildaris, K

    2011-03-01

    This study evaluated the validity, reliability, and sensitivity of the single-trial line drill test (SLDT) for anaerobic power assessment. Twenty-four volunteers were assigned to either a control (C, N.=12) or an experimental (BP, N.=12 basketball players) group. SLDT's (time-to-complete) concurrent validity was evaluated against the Wingate testing (WAnT: mean [MP] and peak power [PP]) and a 30-sec vertical jump testing test (VJT: mean height and MP). Blood lactate concentration was measured at rest and immediately post-test. SLDT's reliability [test-retest intraclass correlation coefficients (ICC), coefficient of variation (CV), Bland-Altman plots] and sensitivity were determined (one-way ANOVA). Kendall's tau correlation analysis revealed correlations (Pbasketball players.

  3. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

    Energy Technology Data Exchange (ETDEWEB)

    Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-04-15

    The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  4. Efficacy of umbilical cord cleansing with a single application of 4% chlorhexidine for the prevention of newborn infections in Uganda: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Nankabirwa, Victoria; Tylleskär, Thorkild; Tumuhamye, Josephine; Tumwine, James K; Ndeezi, Grace; Martines, José C; Sommerfelt, Halvor

    2017-07-12

    Yearly, nearly all the estimated worldwide 2.7 million neonatal deaths occur in low- and middle-income countries. Infections, including those affecting the umbilical cord (omphalitis), are a significant factor in approximately a third of these deaths. In fact, the odds of all-cause mortality are 46% higher among neonates with omphalitis than in those without. Five large randomized controlled trials in Asia and Sub-Saharan Africa (SSA) have examined the effect of multiple cord stump applications with 4% chlorhexidine (CHX) for at least 7 days on the risk of omphalitis and neonatal death. These studies, all community-based, show that multiple CHX applications reduced the risk of omphalitis. Of these trials, only one study from South Asia (the Bangladeshi study) and none from Africa examined the effect of a single application of CHX as soon as possible after birth. In this Bangladeshi trial, CHX led to a reduction in the risk of mild-moderate omphalitis and neonatal death. It is important, in an African setting, to explore the effect of a single application among health-facility births. A single application is programmatically much simpler to implement than daily applications for 7 days. Therefore, our study compares umbilical cord cleansing with a single application of 4% CHX at birth with dry cord care among Ugandan babies born in health facilities, on the risk of omphalitis and severe neonatal illness. The CHX study is a facility-based, individually randomized controlled trial that will be conducted among 4760 newborns in Uganda. The primary outcomes are severe illness and omphalitis during the neonatal period. Analysis will be by intention-to-treat. This study will provide novel evidence, from a Sub-Saharan African setting, of the effect of umbilical cord cleansing with a single application of 4% CHX at birth and identify modifiable risk factors for omphalitis. ClinicalTrials.gov, identifier: NCT02606565 . Registered on 12 November 2015.

  5. Separability of motor imagery of the self from interpretation of motor intentions of others at the single trial level: an EEG study.

    Science.gov (United States)

    Andrade, João; Cecílio, José; Simões, Marco; Sales, Francisco; Castelo-Branco, Miguel

    2017-06-26

    We aimed to investigate the separability of the neural correlates of 2 types of motor imagery, self and third person (actions owned by the participant himself vs. another individual). If possible this would allow for the development of BCI interfaces to train disorders of action and intention understanding beyond simple imitation, such as autism. We used EEG recordings from 20 healthy participants, as well as electrocorticography (ECoG) in one, based on a virtual reality setup. To test feasibility of discrimination between each type of imagery at the single trial level, time-frequency and source analysis were performed and further assessed by data-driven statistical classification using Support Vector Machines. The main observed differences between self-other imagery conditions in topographic maps were found in Frontal and Parieto-Occipital regions, in agreement with the presence of 2 independent non μ related contributions in the low alpha frequency range. ECOG corroborated such separability. Source analysis also showed differences near the temporo-parietal junction and single-trial average classification accuracy between both types of motor imagery was 67 ± 1%, and raised above 70% when 3 trials were used. The single-trial classification accuracy was significantly above chance level for all the participants of this study (p Person MI use distinct electrophysiological mechanisms detectable at the scalp (and ECOG) at the single trial level, with separable levels of involvement of the mirror neuron system in different regions. These observations provide a promising step to develop new BCI training/rehabilitation paradigms for patients with neurodevelopmental disorders of action understanding beyond simple imitation, such as autism, who would benefit from training and anticipation of the perceived intention of others as opposed to own intentions in social contexts.

  6. Single tag for total carbohydrate analysis.

    Science.gov (United States)

    Anumula, Kalyan Rao

    2014-07-15

    Anthranilic acid (2-aminobenzoic acid, 2-AA) has the remarkable property of reacting rapidly with every type of reducing carbohydrate. Reactivity of 2-AA with carbohydrates in aqueous solutions surpasses all other tags reported to date. This unique capability is attributed to the strategically located -COOH which accelerates Schiff base formation. Monosaccharides, oligosaccharides (N-, O-, and lipid linked and glycans in secretory fluids), glycosaminoglycans, and polysaccharides can be easily labeled with 2-AA. With 2-AA, labeling is simple in aqueous solutions containing proteins, peptides, buffer salts, and other ingredients (e.g., PNGase F, glycosidase, and transferase reaction mixtures). In contrast, other tags require relatively pure glycans for labeling in anhydrous dimethyl sulfoxide-acetic acid medium. Acidic conditions are known to cause desialylation, thus requiring a great deal of attention to sample preparation. Simpler labeling is achieved with 2-AA within 30-60 min in mild acetate-borate buffered solution. 2-AA provides the highest sensitivity and resolution in chromatographic methods for carbohydrate analysis in a simple manner. Additionally, 2-AA is uniquely qualified for quantitative analysis by mass spectrometry in the negative mode. Analyses of 2-AA-labeled carbohydrates by electrophoresis and other techniques have been reported. Examples cited here demonstrate that 2-AA is the universal tag for total carbohydrate analysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Social support and education groups for single mothers: a randomized controlled trial of a community-based program.

    Science.gov (United States)

    Lipman, Ellen L; Boyle, Michael H

    2005-12-06

    Members of families headed by single mothers are at increased risk of psychosocial disadvantage and mental health problems. We assessed the effect of a community-based program of social support and education groups for single mothers of young children on maternal well-being and parenting. We recruited 116 single mothers of children 3 to 9 years old through community advertisements. Eligible mothers were randomly assigned either to participate in a 10-week program of group sessions (1.5 hours per week) offering social support and education, with a parallel children's activity group, or to receive a standard list of community resources and the option to participate in group sessions at the end of the follow-up period. Interviewers blinded to the randomization collected assessment data from all mothers at baseline and at 3 follow-up visits (immediately after the intervention and at 3 and 6 months after the intervention). Outcome measures were self-reported mood, self-esteem, social support and parenting. Between February 2000 and April 2003, the program was offered to 9 groups of single mothers. Most of the mothers in the trial reported high levels of financial and mental health problems. In the short term (after the intervention), mothers in the intervention group had improved scores for mood (p effect = 0.55) and self-esteem (p effect = 0.29) compared with mothers in the control group; scores for the other 2 measures did not differ between the groups. Growth curve analysis of program effects over the follow-up period showed improvement in all 4 outcomes, with no significant difference between the intervention and control groups. This community-based program of group sessions offering social support and education to low-income single mothers had positive short-term effects on mood and self-esteem but not on social support and parenting. Longer follow-up showed attenuation of these effects.

  8. How attention influences perceptual decision making: Single-trial EEG correlates of drift-diffusion model parameters

    Science.gov (United States)

    Nunez, Michael D.; Vandekerckhove, Joachim; Srinivasan, Ramesh

    2016-01-01

    Perceptual decision making can be accounted for by drift-diffusion models, a class of decision-making models that assume a stochastic accumulation of evidence on each trial. Fitting response time and accuracy to a drift-diffusion model produces evidence accumulation rate and non-decision time parameter estimates that reflect cognitive processes. Our goal is to elucidate the effect of attention on visual decision making. In this study, we show that measures of attention obtained from simultaneous EEG recordings can explain per-trial evidence accumulation rates and perceptual preprocessing times during a visual decision making task. Models assuming linear relationships between diffusion model parameters and EEG measures as external inputs were fit in a single step in a hierarchical Bayesian framework. The EEG measures were features of the evoked potential (EP) to the onset of a masking noise and the onset of a task-relevant signal stimulus. Single-trial evoked EEG responses, P200s to the onsets of visual noise and N200s to the onsets of visual signal, explain single-trial evidence accumulation and preprocessing times. Within-trial evidence accumulation variance was not found to be influenced by attention to the signal or noise. Single-trial measures of attention lead to better out-of-sample predictions of accuracy and correct reaction time distributions for individual subjects. PMID:28435173

  9. How attention influences perceptual decision making: Single-trial EEG correlates of drift-diffusion model parameters.

    Science.gov (United States)

    Nunez, Michael D; Vandekerckhove, Joachim; Srinivasan, Ramesh

    2017-02-01

    Perceptual decision making can be accounted for by drift-diffusion models, a class of decision-making models that assume a stochastic accumulation of evidence on each trial. Fitting response time and accuracy to a drift-diffusion model produces evidence accumulation rate and non-decision time parameter estimates that reflect cognitive processes. Our goal is to elucidate the effect of attention on visual decision making. In this study, we show that measures of attention obtained from simultaneous EEG recordings can explain per-trial evidence accumulation rates and perceptual preprocessing times during a visual decision making task. Models assuming linear relationships between diffusion model parameters and EEG measures as external inputs were fit in a single step in a hierarchical Bayesian framework. The EEG measures were features of the evoked potential (EP) to the onset of a masking noise and the onset of a task-relevant signal stimulus. Single-trial evoked EEG responses, P200s to the onsets of visual noise and N200s to the onsets of visual signal, explain single-trial evidence accumulation and preprocessing times. Within-trial evidence accumulation variance was not found to be influenced by attention to the signal or noise. Single-trial measures of attention lead to better out-of-sample predictions of accuracy and correct reaction time distributions for individual subjects.

  10. Applicability of supervised discriminant analysis models to analyze astigmatism clinical trial data

    Directory of Open Access Journals (Sweden)

    Sedghipour MR

    2012-09-01

    Full Text Available Mohammad Reza Sedghipour,1 Homayoun Sadeghi-Bazargani2,31Nikoukari Ophthalmology University Hospital, Tabriz, Iran; 2Department of Statistics and Epidemiology, Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; 3Department of Public Health Sciences, Karolinska Institute, Stockholm, SwedenBackground: In astigmatism clinical trials where more complex measurements are common, especially in nonrandomized small sized clinical trials, there is a demand for the development and application of newer statistical methods.Methods: The source data belonged to a project on astigmatism treatment. Data were used regarding a total of 296 eyes undergoing different astigmatism treatment modalities: wavefront-guided photorefractive keratectomy, cross-cylinder photorefractive keratectomy, and monotoric (single photorefractive keratectomy. Astigmatism analysis was primarily done using the Alpins method. Prior to fitting partial least squares regression discriminant analysis, a preliminary principal component analysis was done for data overview. Through fitting the partial least squares regression discriminant analysis statistical method, various model validity and predictability measures were assessed.Results: The model found the patients treated by the wavefront method to be different from the two other treatments both in baseline and outcome measures. Also, the model found that patients treated with the cross-cylinder method versus the single method didn't appear to be different from each other. This analysis provided an opportunity to compare the three methods while including a substantial number of baseline and outcome variables.Conclusion: Partial least squares regression discriminant analysis had applicability for the statistical analysis of astigmatism clinical trials and it may be used as an adjunct or alternative analysis method in small sized clinical trials.Keywords: astigmatism, regression, partial least squares regression

  11. Analysis of Single Coil PM-BLDC Motor

    Directory of Open Access Journals (Sweden)

    Boguslaw Grzesik

    2012-06-01

    Full Text Available The aim of the paper is FEM analysis of single coil BLDC motor operated as drive of small piston pump. The paper contains analysis of design, distribution of magnetic field, forces and torque under static and dynamic conditions. Voltages, currents, signals waveforms are also given as the results of analysis. The cogging torque and total torque are discussed in the paper.

  12. The FINISH-3 Trial : A Phase 3, International, Randomized, Single-Blind, Controlled Trial of Topical Fibrocaps in Intraoperative Surgical Hemostasis

    NARCIS (Netherlands)

    Bochicchio, Grant V.; Gupta, Navyash; Porte, Robert J.; Renkens, Kenneth L.; Pattyn, Piet; Topal, Baki; Troisi, Roberto Ivan; Muir, William; Chetter, Ian; Gillen, Daniel L.; Zuckerman, Linda A.; Frohna, Paul A.

    BACKGROUND: This Phase 3, international, randomized, single-blind, controlled trial (FINISH-3) compared the efficacy and safety of Fibrocaps, a ready-to-use, dry-powder fibrin sealant containing human plasma-derived thrombin and fibrinogen, vs gelatin sponge alone for use as a hemostat for surgical

  13. Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

    Science.gov (United States)

    Sivaramakrishnan, Gowri; Sridharan, Kannan

    2016-06-01

    Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

  14. Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis.

    Science.gov (United States)

    Calabrese, C; Tosco, A; Abete, P; Carnovale, V; Basile, C; Magliocca, A; Quattrucci, S; De Sanctis, S; Alatri, F; Mazzarella, G; De Pietro, L; Turino, C; Melillo, E; Buonpensiero, P; Di Pasqua, A; Raia, V

    2015-03-01

    In cystic fibrosis (CF) the defective CF transmembrane conductance regulator protein may be responsible for the impaired transport of glutathione (GSH), the first line defense of the lung against oxidative stress. The aim of this single-blind, randomized, placebo-controlled trial was to evaluate the effect of inhaled GSH in patients with CF. 54 adult and 51 pediatric patients were randomized to receive inhaled GSH or placebo twice daily for 12 months. Twelve month treatment with inhaled GSH did not achieve our predetermined primary outcome measure of 15% improvement in FEV1%. Only in patients with moderate lung disease, 3, 6 and 9 months therapy with GSH resulted in a statistically significant increase of FEV1 values from the baseline. Moreover GSH therapy improved 6-minute walking test in pediatric population. GSH was well tolerated by all patients. Inhaled GSH has slight positive effects in CF patients with moderate lung disease warranting further study. ClinicalTrials.gov; No.: NCT01450267; URL: www.clinicaltrialsgov. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. A single-blinded randomised clinical trial of permissive underfeeding in patients requiring parenteral nutrition.

    Science.gov (United States)

    Owais, Anwar Elias; Kabir, Syed Irfan; Mcnaught, Clare; Gatt, Marcel; MacFie, John

    2014-12-01

    The importance of adequate nutritional support is well established, but characterising what 'adequate nutrition' represents remains contentious. In recent years there has been increasing interest in the concept of 'permissive underfeeding' where patients are intentionally prescribed less nutrition than their calculated requirements. The aim of this study was to evaluate the effect of permissive underfeeding on septic and nutrition related morbidity in patients requiring short term parenteral nutrition (PN). This was a single-blinded randomised clinical trial of 50 consecutive patients requiring parenteral nutritional support. Patients were randomized to receive either normocaloric or hypocaloric feeding (respectively 100% vs. 60% of estimated requirements). The primary end point was septic complications. Secondary end points included the metabolic, physiological and clinical outcomes to the two feeding protocols. Permissive underfeeding was associated with fewer septic complications (3 vs. 12 patients; p = 0.003), and a lower incidence of the systemic inflammatory response syndrome (9 vs. 16 patients; p = 0.017). Permissively underfed patients had fewer feed related complications (2 vs. 9 patients; p = 0.016). Permissive underfeeding in patients requiring short term PN appears to be safe and may results in reduced septic and feed-related complications. NCT01154179 TRIAL REGISTRY: http://clinicaltrials.gov/ct2/show/NCT01154179. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  16. Single-shell tank interim stabilization risk analysis

    International Nuclear Information System (INIS)

    Basche, A.D.

    1998-01-01

    The purpose of the Single-Shell Tank (SST) Interim Stabilization Risk Analysis is to provide a cost and schedule risk analysis of HNF-2358, Rev. 1, Single-Shell Tank Interim Stabilization Project Plan (Project Plan) (Ross et al. 1998). The analysis compares the required cost profile by fiscal year (Section 4.2) and revised schedule completion date (Section 4.5) to the Project Plan. The analysis also evaluates the executability of the Project Plan and recommends a path forward for risk mitigation

  17. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

    Science.gov (United States)

    Dunning, Jake; Sahr, Foday; Rojek, Amanda; Gannon, Fiona; Carson, Gail; Idriss, Baimba; Massaquoi, Thomas; Gandi, Regina; Joseph, Sebatu; Osman, Hassan K; Brooks, Timothy J G; Simpson, Andrew J H; Goodfellow, Ian; Thorne, Lucy; Arias, Armando; Merson, Laura; Castle, Lyndsey; Howell-Jones, Rebecca; Pardinaz-Solis, Raul; Hope-Gill, Benjamin; Ferri, Mauricio; Grove, Jennifer; Kowalski, Mark; Stepniewska, Kasia; Lang, Trudie; Whitehead, John; Olliaro, Piero; Samai, Mohammed; Horby, Peter W

    2016-04-01

    TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. Pan African Clinical Trials Registry PACTR201501000997429.

  18. [Economic analysis of multinational clinical trials in oncology].

    Science.gov (United States)

    Lejeune, Catherine; Lueza, Béranger; Bonastre, Julia

    2018-02-01

    In oncology, as in other fields of medicine, international multicentre clinical trials came into being so as to include a sufficient number of subjects to investigate a clinical situation. The existence of tight budgetary constraints and the desire to make the best use of the resources available have resulted in the development of economic evaluations associated with these trials, which, thanks to their level of evidence and their size, provide particularly relevant material. Nonetheless, economic evaluations alongside international clinical trials raise specific questions of methodology with regard to both the design and the analysis of the results. Indeed, the costs of goods and services consumed, the types and quantities of resources, and medical practices vary from one country to another and within an individual country. Economic data from the different countries involved must be available so as to study and to take into account this variability, and appropriate techniques for cost estimations and analysis must be implemented to aggregate the results from several countries. From a review of the literature, the aim of this work was to provide an overview of the specific methodological features of economic evaluations alongside international clinical trials: analysis of efficacy data from several countries, collection of resources and real costs, methods to establish the monetary value of resources, methods to aggregate results accounting for the trial effect. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. Glucocorticosteroids for sepsis : systematic review with meta-analysis and trial sequential analysis

    NARCIS (Netherlands)

    Volbeda, M.; Wetterslev, J.; Gluud, C.; Zijlstra, J. G.; van der Horst, I. C. C.; Keus, F.

    Glucocorticosteroids (steroids) are widely used for sepsis patients. However, the potential benefits and harms of both high and low dose steroids remain unclear. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis (TSA) might shed light on this

  20. A single point acupuncture treatment at large intestine meridian: a randomized controlled trial in acute tonsillitis and pharyngitis.

    Science.gov (United States)

    Fleckenstein, Johannes; Lill, Christian; Lüdtke, Rainer; Gleditsch, Jochen; Rasp, Gerd; Irnich, Dominik

    2009-09-01

    One out of 4 patients visiting a general practitioner reports of a sore throat associated with pain on swallowing. This study was established to examine the immediate pain alleviating effect of a single point acupuncture treatment applied to the large intestine meridian of patients with sore throat. Sixty patients with acute tonsillitis and pharyngitis were enrolled in this randomized placebo-controlled trial. They either received acupuncture, or sham laser acupuncture, directed to the large intestine meridian section between acupuncture points LI 8 and LI 10. The main outcome measure was the change of pain intensity on swallowing a sip of water evaluated by a visual analog scale 15 minutes after treatment. A credibility assessment regarding the respective treatment was performed. The pain intensity for the acupuncture group before and immediately after therapy was 5.6+/-2.8 and 3.0+/-3.0, and for the sham group 5.6+/-2.5 and 3.8+/-2.5, respectively. Despite the articulation of a more pronounced improvement among the acupuncture group, there was no significant difference between groups (Delta=0.9, confidence interval: -0.2-2.0; P=0.12; analysis of covariance). Patients' satisfaction was high in both treatment groups. The study was prematurely terminated due to a subsequent lack of suitable patients. A single acupuncture treatment applied to a selected area of the large intestine meridian was no more effective in the alleviation of pain associated with clinical sore throat than sham laser acupuncture applied to the same area. Hence, clinically relevant improvement could be achieved. Pain alleviation might partly be due to the intense palpation of the large intestine meridian. The benefit of a comprehensive acupuncture treatment protocol in this condition should be subject to further trials.

  1. Classification of Single-Trial Auditory Events Using Dry-Wireless EEG During Real and Motion Simulated Flight

    Directory of Open Access Journals (Sweden)

    Daniel eCallan

    2015-02-01

    Full Text Available Application of neuro-augmentation technology based on dry-wireless EEG may be considerably beneficial for aviation and space operations because of the inherent dangers involved. In this study we evaluate classification performance of perceptual events using a dry-wireless EEG system during motion platform based flight simulation and actual flight in an open cockpit biplane to determine if the system can be used in the presence of considerable environmental and physiological artifacts. A passive task involving 200 random auditory presentations of a chirp sound was used for evaluation. The advantage of this auditory task is that it does not interfere with the perceptual motor processes involved with piloting the plane. Classification was based on identifying the presentation of a chirp sound versus silent periods. Evaluation of Independent component analysis and Kalman filtering to enhance classification performance by extracting brain activity related to the auditory event from other non-task related brain activity and artifacts was assessed. The results of permutation testing revealed that single trial classification of presence or absence of an auditory event was significantly above chance for all conditions on a novel test set. The best performance could be achieved with both ICA and Kalman filtering relative to no processing: Platform Off (83.4% vs 78.3%, Platform On (73.1% vs 71.6%, Biplane Engine Off (81.1% vs 77.4%, and Biplane Engine On (79.2% vs 66.1%. This experiment demonstrates that dry-wireless EEG can be used in environments with considerable vibration, wind, acoustic noise, and physiological artifacts and achieve good single trial classification performance that is necessary for future successful application of neuro-augmentation technology based on brain-machine interfaces.

  2. Identification of Auditory Object-Specific Attention from Single-Trial Electroencephalogram Signals via Entropy Measures and Machine Learning

    Directory of Open Access Journals (Sweden)

    Yun Lu

    2018-05-01

    Full Text Available Existing research has revealed that auditory attention can be tracked from ongoing electroencephalography (EEG signals. The aim of this novel study was to investigate the identification of peoples’ attention to a specific auditory object from single-trial EEG signals via entropy measures and machine learning. Approximate entropy (ApEn, sample entropy (SampEn, composite multiscale entropy (CmpMSE and fuzzy entropy (FuzzyEn were used to extract the informative features of EEG signals under three kinds of auditory object-specific attention (Rest, Auditory Object1 Attention (AOA1 and Auditory Object2 Attention (AOA2. The linear discriminant analysis and support vector machine (SVM, were used to construct two auditory attention classifiers. The statistical results of entropy measures indicated that there were significant differences in the values of ApEn, SampEn, CmpMSE and FuzzyEn between Rest, AOA1 and AOA2. For the SVM-based auditory attention classifier, the auditory object-specific attention of Rest, AOA1 and AOA2 could be identified from EEG signals using ApEn, SampEn, CmpMSE and FuzzyEn as features and the identification rates were significantly different from chance level. The optimal identification was achieved by the SVM-based auditory attention classifier using CmpMSE with the scale factor τ = 10. This study demonstrated a novel solution to identify the auditory object-specific attention from single-trial EEG signals without the need to access the auditory stimulus.

  3. Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis.

    Science.gov (United States)

    Drabble, Sarah J; O'Cathain, Alicia; Thomas, Kate J; Rudolph, Anne; Hewison, Jenny

    2014-02-18

    There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for doing the qualitative research and

  4. Describing qualitative research undertaken with randomised controlled trials in grant proposals: a documentary analysis

    Science.gov (United States)

    2014-01-01

    Background There is growing recognition of the value of conducting qualitative research with trials in health research. It is timely to reflect on how this qualitative research is presented in grant proposals to identify lessons for researchers and research commissioners. As part of a larger study focusing on how to maximise the value of undertaking qualitative research with trials, we undertook a documentary analysis of proposals of funded studies. Methods Using the metaRegister of Controlled Trials (mRCT) database we identified trials funded in the United Kingdom, ongoing between 2001 and 2010, and reporting the use of qualitative research. We requested copies of proposals from lead researchers. We extracted data from the proposals using closed and open questions, analysed using descriptive statistics and content analysis respectively. Results 2% (89/3812) of trials in the mRCT database described the use of qualitative research undertaken with the trial. From these 89 trials, we received copies of 36 full proposals, of which 32 met our inclusion criteria. 25% used less than a single paragraph to describe the qualitative research. The aims of the qualitative research described in these proposals focused mainly on the intervention or trial conduct. Just over half (56%) of the proposals included an explicit rationale for conducting the qualitative research with the trial, the most frequent being to optimise implementation into clinical practice or to interpret trial findings. Key information about methods, expertise and resources was missing in a large minority of proposals, in particular sample size, type of analysis, and non-personnel resources. 28% specifically stated that qualitative researchers would conduct the qualitative research. Conclusions Our review of proposals of successfully funded studies identified good practice but also identified limited space given to describing the qualitative research, with an associated lack of attention to the rationale for

  5. An automated and fast approach to detect single-trial visual evoked potentials with application to brain-computer interface.

    Science.gov (United States)

    Tu, Yiheng; Hung, Yeung Sam; Hu, Li; Huang, Gan; Hu, Yong; Zhang, Zhiguo

    2014-12-01

    This study aims (1) to develop an automated and fast approach for detecting visual evoked potentials (VEPs) in single trials and (2) to apply the single-trial VEP detection approach in designing a real-time and high-performance brain-computer interface (BCI) system. The single-trial VEP detection approach uses common spatial pattern (CSP) as a spatial filter and wavelet filtering (WF) a temporal-spectral filter to jointly enhance the signal-to-noise ratio (SNR) of single-trial VEPs. The performance of the joint spatial-temporal-spectral filtering approach was assessed in a four-command VEP-based BCI system. The offline classification accuracy of the BCI system was significantly improved from 67.6±12.5% (raw data) to 97.3±2.1% (data filtered by CSP and WF). The proposed approach was successfully implemented in an online BCI system, where subjects could make 20 decisions in one minute with classification accuracy of 90%. The proposed single-trial detection approach is able to obtain robust and reliable VEP waveform in an automatic and fast way and it is applicable in VEP based online BCI systems. This approach provides a real-time and automated solution for single-trial detection of evoked potentials or event-related potentials (EPs/ERPs) in various paradigms, which could benefit many applications such as BCI and intraoperative monitoring. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Competing events and costs of clinical trials: Analysis of a randomized trial in prostate cancer

    International Nuclear Information System (INIS)

    Zakeri, Kaveh; Rose, Brent S.; D’Amico, Anthony V.; Jeong, Jong-Hyeon; Mell, Loren K.

    2015-01-01

    Background: Clinical trial costs may be reduced by identifying enriched subpopulations of patients with favorable risk profiles for the events of interest. However, increased selectivity affects accrual rates, with uncertain impact on clinical trial cost. Methods: We conducted a secondary analysis of Southwest Oncology Group (SWOG) 8794 randomized trial of adjuvant radiotherapy for high-risk prostate cancer. The primary endpoint was metastasis-free survival (MFS), defined as time to metastasis or death from any cause (competing mortality). We used competing risks regression models to identify an enriched subgroup at high risk for metastasis and low risk for competing mortality. We applied a cost model to estimate the impact of enrichment on trial cost and duration. Results: The treatment effect on metastasis was similar in the enriched subgroup (HR, 0.42; 95% CI, 0.23–0.76) compared to the whole cohort (HR, 0.50; 95% CI, 0.30–0.81) while the effect on competing mortality was not significant in the subgroup or the whole cohort (HR 0.70; 95% CI 0.39–1.23, vs. HR 0.94; 95% CI, 0.68–1.31). Due to the higher incidence of metastasis relative to competing mortality in the enriched subgroup, the treatment effect on MFS was greater in the subgroup compared to the whole cohort (HR 0.55; 95% CI 0.36–0.82, vs. HR 0.77; 95% CI, 0.58–1.01). Trial cost was 75% less in the subgroup compared to the whole cohort ($1.7 million vs. $6.8 million), and the trial duration was 30% shorter (8.4 vs. 12.0 years). Conclusion: Competing event enrichment can reduce clinical trial cost and duration, without sacrificing generalizability

  7. Single-Use Energy Sources and Operating Room Time for Laparoscopic Hysterectomy: A Randomized Controlled Trial.

    Science.gov (United States)

    Holloran-Schwartz, M Brigid; Gavard, Jeffrey A; Martin, Jared C; Blaskiewicz, Robert J; Yeung, Patrick P

    2016-01-01

    To compare the intraoperative direct costs of a single-use energy device with reusable energy devices during laparoscopic hysterectomy. A randomized controlled trial (Canadian Task Force Classification I). An academic hospital. Forty-six women who underwent laparoscopic hysterectomy from March 2013 to September 2013. Each patient served as her own control. One side of the uterine attachments was desiccated and transected with the single-use device (Ligasure 5-mm Blunt Tip LF1537 with the Force Triad generator). The other side was desiccated and transected with reusable bipolar forceps (RoBi 5 mm), and transected with monopolar scissors using the same Covidien Force Triad generator. The instrument approach used was randomized to the attending physician who was always on the patient's left side. Resident physicians always operated on the patient's right side and used the converse instruments of the attending physician. Start time was recorded at the utero-ovarian pedicle and end time was recorded after transection of the uterine artery on the same side. Costs included the single-use device; amortized costs of the generator, reusable instruments, and cords; cleaning and packaging of reusable instruments; and disposal of the single-use device. Operating room time was $94.14/min. We estimated that our single use-device cost $630.14 and had a total time savings of 6.7 min per case, or 3.35 min per side, which could justify the expense of the device. The single-use energy device had significant median time savings (-4.7 min per side, p energy device that both desiccates and cuts significantly reduced operating room time to justify its own cost, and it also reduced total intraoperative direct costs during laparoscopic hysterectomy in our institution. Operating room cost per minute varies between institutions and must be considered before generalizing our results. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  8. Australasian Resuscitation In Sepsis Evaluation trial statistical analysis plan.

    Science.gov (United States)

    Delaney, Anthony; Peake, Sandra L; Bellomo, Rinaldo; Cameron, Peter; Holdgate, Anna; Howe, Belinda; Higgins, Alisa; Presneill, Jeffrey; Webb, Steve

    2013-10-01

    The Australasian Resuscitation In Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the ED with severe sepsis. In keeping with current practice, and taking into considerations aspects of trial design and reporting specific to non-pharmacologic interventions, this document outlines the principles and methods for analysing and reporting the trial results. The document is prepared prior to completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and prior to completion of the two related international studies. The statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. The data collected by the research team as specified in the study protocol, and detailed in the study case report form were reviewed. Information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation and other related therapies, and other relevant data are described with appropriate comparisons between groups. The primary, secondary and tertiary outcomes for the study are defined, with description of the planned statistical analyses. A statistical analysis plan was developed, along with a trial profile, mock-up tables and figures. A plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies, along with adverse events are described. The primary, secondary and tertiary outcomes are described along with identification of subgroups to be analysed. A statistical analysis plan for the ARISE study has been developed, and is available in the public domain, prior to the completion of recruitment into the

  9. Design, analysis and presentation of factorial randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Little Paul

    2003-11-01

    Full Text Available Abstract Background The evaluation of more than one intervention in the same randomised controlled trial can be achieved using a parallel group design. However this requires increased sample size and can be inefficient, especially if there is also interest in considering combinations of the interventions. An alternative may be a factorial trial, where for two interventions participants are allocated to receive neither intervention, one or the other, or both. Factorial trials require special considerations, however, particularly at the design and analysis stages. Discussion Using a 2 × 2 factorial trial as an example, we present a number of issues that should be considered when planning a factorial trial. The main design issue is that of sample size. Factorial trials are most often powered to detect the main effects of interventions, since adequate power to detect plausible interactions requires greatly increased sample sizes. The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models. Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions. We also give an example of how baseline and follow-up data should be presented. Lastly, we discuss the implications of the design, analytical and presentational issues covered. Summary Difficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient, simultaneous consideration of two or more interventions. Factorial trials can in principle be designed to have adequate power to detect realistic interactions, and in any case they are the only design that allows such effects to be investigated.

  10. Development of a Multi-Centre Clinical Trial Data Archiving and Analysis Platform for Functional Imaging

    Science.gov (United States)

    Driscoll, Brandon; Jaffray, David; Coolens, Catherine

    2014-03-01

    Purpose: To provide clinicians & researchers participating in multi-centre clinical trials with a central repository for large volume dynamic imaging data as well as a set of tools for providing end-to-end testing and image analysis standards of practice. Methods: There are three main pieces to the data archiving and analysis system; the PACS server, the data analysis computer(s) and the high-speed networks that connect them. Each clinical trial is anonymized using a customizable anonymizer and is stored on a PACS only accessible by AE title access control. The remote analysis station consists of a single virtual machine per trial running on a powerful PC supporting multiple simultaneous instances. Imaging data management and analysis is performed within ClearCanvas Workstation® using custom designed plug-ins for kinetic modelling (The DCE-Tool®), quality assurance (The DCE-QA Tool) and RECIST. Results: A framework has been set up currently serving seven clinical trials spanning five hospitals with three more trials to be added over the next six months. After initial rapid image transfer (+ 2 MB/s), all data analysis is done server side making it robust and rapid. This has provided the ability to perform computationally expensive operations such as voxel-wise kinetic modelling on very large data archives (+20 GB/50k images/patient) remotely with minimal end-user hardware. Conclusions: This system is currently in its proof of concept stage but has been used successfully to send and analyze data from remote hospitals. Next steps will involve scaling up the system with a more powerful PACS and multiple high powered analysis machines as well as adding real-time review capabilities.

  11. Development of a Multi-Centre Clinical Trial Data Archiving and Analysis Platform for Functional Imaging

    International Nuclear Information System (INIS)

    Driscoll, Brandon; Jaffray, David; Coolens, Catherine

    2014-01-01

    Purpose: To provide clinicians and researchers participating in multi-centre clinical trials with a central repository for large volume dynamic imaging data as well as a set of tools for providing end-to-end testing and image analysis standards of practice. Methods: There are three main pieces to the data archiving and analysis system; the PACS server, the data analysis computer(s) and the high-speed networks that connect them. Each clinical trial is anonymized using a customizable anonymizer and is stored on a PACS only accessible by AE title access control. The remote analysis station consists of a single virtual machine per trial running on a powerful PC supporting multiple simultaneous instances. Imaging data management and analysis is performed within ClearCanvas Workstation® using custom designed plug-ins for kinetic modelling (The DCE-Tool®), quality assurance (The DCE-QA Tool) and RECIST. Results: A framework has been set up currently serving seven clinical trials spanning five hospitals with three more trials to be added over the next six months. After initial rapid image transfer (+ 2 MB/s), all data analysis is done server side making it robust and rapid. This has provided the ability to perform computationally expensive operations such as voxel-wise kinetic modelling on very large data archives (+20 GB/50k images/patient) remotely with minimal end-user hardware. Conclusions: This system is currently in its proof of concept stage but has been used successfully to send and analyze data from remote hospitals. Next steps will involve scaling up the system with a more powerful PACS and multiple high powered analysis machines as well as adding real-time review capabilities.

  12. Benign painful shoulder syndrome. Initial results of a single-center prospective randomized radiotherapy dose-optimization trial

    International Nuclear Information System (INIS)

    Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

    2012-01-01

    Background and purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Patients and methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  13. Bioinformatics approaches to single-cell analysis in developmental biology.

    Science.gov (United States)

    Yalcin, Dicle; Hakguder, Zeynep M; Otu, Hasan H

    2016-03-01

    Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology. © The Author 2015. Published by Oxford University Press on behalf of the European

  14. Single cell analysis of normal and leukemic hematopoiesis.

    Science.gov (United States)

    Povinelli, Benjamin J; Rodriguez-Meira, Alba; Mead, Adam J

    2018-02-01

    The hematopoietic system is well established as a paradigm for the study of cellular hierarchies, their disruption in disease and therapeutic use in regenerative medicine. Traditional approaches to study hematopoiesis involve purification of cell populations based on a small number of surface markers. However, such population-based analysis obscures underlying heterogeneity contained within any phenotypically defined cell population. This heterogeneity can only be resolved through single cell analysis. Recent advances in single cell techniques allow analysis of the genome, transcriptome, epigenome and proteome in single cells at an unprecedented scale. The application of these new single cell methods to investigate the hematopoietic system has led to paradigm shifts in our understanding of cellular heterogeneity in hematopoiesis and how this is disrupted in disease. In this review, we summarize how single cell techniques have been applied to the analysis of hematopoietic stem/progenitor cells in normal and malignant hematopoiesis, with a particular focus on recent advances in single-cell genomics, including how these might be utilized for clinical application. Copyright © 2017. Published by Elsevier Ltd.

  15. Single-shell tank retrieval program mission analysis report

    International Nuclear Information System (INIS)

    Stokes, W.J.

    1998-01-01

    This Mission Analysis Report was prepared to provide the foundation for the Single-Shell Tank (SST) Retrieval Program, a new program responsible for waste removal for the SSTS. The SST Retrieval Program is integrated with other Tank Waste Remediation System activities that provide the management, technical, and operations elements associated with planning and execution of SST and SST Farm retrieval and closure. This Mission Analysis Report provides the basis and strategy for developing a program plan for SST retrieval. This Mission Analysis Report responds to a US Department of Energy request for an alternative single-shell tank retrieval approach (Taylor 1997)

  16. Single-shell tank retrieval program mission analysis report

    Energy Technology Data Exchange (ETDEWEB)

    Stokes, W.J.

    1998-08-11

    This Mission Analysis Report was prepared to provide the foundation for the Single-Shell Tank (SST) Retrieval Program, a new program responsible for waste removal for the SSTS. The SST Retrieval Program is integrated with other Tank Waste Remediation System activities that provide the management, technical, and operations elements associated with planning and execution of SST and SST Farm retrieval and closure. This Mission Analysis Report provides the basis and strategy for developing a program plan for SST retrieval. This Mission Analysis Report responds to a US Department of Energy request for an alternative single-shell tank retrieval approach (Taylor 1997).

  17. A single-chip computer analysis system for liquid fluorescence

    International Nuclear Information System (INIS)

    Zhang Yongming; Wu Ruisheng; Li Bin

    1998-01-01

    The single-chip computer analysis system for liquid fluorescence is an intelligent analytic instrument, which is based on the principle that the liquid containing hydrocarbons can give out several characteristic fluorescences when irradiated by strong light. Besides a single-chip computer, the system makes use of the keyboard and the calculation and printing functions of a CASIO printing calculator. It combines optics, mechanism and electronics into one, and is small, light and practical, so it can be used for surface water sample analysis in oil field and impurity analysis of other materials

  18. Quantitative high-resolution genomic analysis of single cancer cells.

    Science.gov (United States)

    Hannemann, Juliane; Meyer-Staeckling, Sönke; Kemming, Dirk; Alpers, Iris; Joosse, Simon A; Pospisil, Heike; Kurtz, Stefan; Görndt, Jennifer; Püschel, Klaus; Riethdorf, Sabine; Pantel, Klaus; Brandt, Burkhard

    2011-01-01

    During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics.

  19. Quantitative high-resolution genomic analysis of single cancer cells.

    Directory of Open Access Journals (Sweden)

    Juliane Hannemann

    Full Text Available During cancer progression, specific genomic aberrations arise that can determine the scope of the disease and can be used as predictive or prognostic markers. The detection of specific gene amplifications or deletions in single blood-borne or disseminated tumour cells that may give rise to the development of metastases is of great clinical interest but technically challenging. In this study, we present a method for quantitative high-resolution genomic analysis of single cells. Cells were isolated under permanent microscopic control followed by high-fidelity whole genome amplification and subsequent analyses by fine tiling array-CGH and qPCR. The assay was applied to single breast cancer cells to analyze the chromosomal region centred by the therapeutical relevant EGFR gene. This method allows precise quantitative analysis of copy number variations in single cell diagnostics.

  20. Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation

    Directory of Open Access Journals (Sweden)

    John A Zawadzki

    2013-11-01

    Full Text Available Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia that would complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogues.Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position. Results: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning. Conclusion: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.

  1. Decision on performing interim analysis for comparative clinical trials.

    Science.gov (United States)

    Pak, Kyongsun; Jacobus, Susanna; Uno, Hajime

    2017-09-01

    In randomized-controlled trials, interim analyses are often planned for possible early trial termination to claim superiority or futility of a new therapy. While unblinding is necessary to conduct the formal interim analysis in blinded studies, blinded data also have information about the potential treatment difference between the groups. We developed a blinded data monitoring tool that enables investigators to predict whether they observe such an unblinded interim analysis results that supports early termination of the trial. Investigators may skip some of the planned interim analyses if an early termination is unlikely. We specifically focused on blinded, randomized-controlled studies to compare binary endpoints of a new treatment with a control. Assuming one interim analysis is planned for early termination for superiority or futility, we conducted extensive simulation studies to assess the impact of the implementation of our tool on the size, power, expected number of interim analyses, and bias in the treatment effect. The numerical study showed the proposed monitoring tool does not affect size or power, but dramatically reduces the expected number of interim analyses when the effect of the treatment difference is small. The tool serves as a useful reference when interpreting the summary of the blinded data throughout the course of the trial, without losing integrity of the study. This tool could potentially save the study resources and budget by avoiding unnecessary interim analyses.

  2. Multi-Tasking and Choice of Training Data Influencing Parietal ERP Expression and Single-Trial Detection—Relevance for Neuroscience and Clinical Applications

    Science.gov (United States)

    Kirchner, Elsa A.; Kim, Su Kyoung

    2018-01-01

    Event-related potentials (ERPs) are often used in brain-computer interfaces (BCIs) for communication or system control for enhancing or regaining control for motor-disabled persons. Especially results from single-trial EEG classification approaches for BCIs support correlations between single-trial ERP detection performance and ERP expression. Hence, BCIs can be considered as a paradigm shift contributing to new methods with strong influence on both neuroscience and clinical applications. Here, we investigate the relevance of the choice of training data and classifier transfer for the interpretability of results from single-trial ERP detection. In our experiments, subjects performed a visual-motor oddball task with motor-task relevant infrequent (targets), motor-task irrelevant infrequent (deviants), and motor-task irrelevant frequent (standards) stimuli. Under dual-task condition, a secondary senso-motor task was performed, compared to the simple-task condition. For evaluation, average ERP analysis and single-trial detection analysis with different numbers of electrodes were performed. Further, classifier transfer was investigated between simple and dual task. Parietal positive ERPs evoked by target stimuli (but not by deviants) were expressed stronger under dual-task condition, which is discussed as an increase of task emphasis and brain processes involved in task coordination and change of task set. Highest classification performance was found for targets irrespective whether all 62, 6 or 2 parietal electrodes were used. Further, higher detection performance of targets compared to standards was achieved under dual-task compared to simple-task condition in case of training on data from 2 parietal electrodes corresponding to results of ERP average analysis. Classifier transfer between tasks improves classification performance in case that training took place on more varying examples (from dual task). In summary, we showed that P300 and overlaying parietal positive

  3. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial

    NARCIS (Netherlands)

    Homs, Marjolein Y. V.; Steyerberg, Ewout W.; Eijkenboom, Wilhelmina M. H.; Tilanus, Hugo W.; Stalpers, Lukas J. A.; Bartelsman, Joep F. W. M.; van Lanschot, Jan J. B.; Wijrdeman, Harm K.; Mulder, Chris J. J.; Reinders, Janny G.; Boot, Henk; Aleman, Berthe M. P.; Kuipers, Ernst J.; Siersema, Peter D.

    2004-01-01

    Background Both single-dose brachytherapy and self-expanding metal stent placement are commonly used for palliation of oesophageal obstruction due to inoperable cancer, but their relative merits are unknown. We under-took a randomised trial to compare the outcomes of brachytherapy and stent

  4. Platforms for Single-Cell Collection and Analysis

    Directory of Open Access Journals (Sweden)

    Lukas Valihrach

    2018-03-01

    Full Text Available Single-cell analysis has become an established method to study cell heterogeneity and for rare cell characterization. Despite the high cost and technical constraints, applications are increasing every year in all fields of biology. Following the trend, there is a tremendous development of tools for single-cell analysis, especially in the RNA sequencing field. Every improvement increases sensitivity and throughput. Collecting a large amount of data also stimulates the development of new approaches for bioinformatic analysis and interpretation. However, the essential requirement for any analysis is the collection of single cells of high quality. The single-cell isolation must be fast, effective, and gentle to maintain the native expression profiles. Classical methods for single-cell isolation are micromanipulation, microdissection, and fluorescence-activated cell sorting (FACS. In the last decade several new and highly efficient approaches have been developed, which not just supplement but may fully replace the traditional ones. These new techniques are based on microfluidic chips, droplets, micro-well plates, and automatic collection of cells using capillaries, magnets, an electric field, or a punching probe. In this review we summarize the current methods and developments in this field. We discuss the advantages of the different commercially available platforms and their applicability, and also provide remarks on future developments.

  5. Platforms for Single-Cell Collection and Analysis.

    Science.gov (United States)

    Valihrach, Lukas; Androvic, Peter; Kubista, Mikael

    2018-03-11

    Single-cell analysis has become an established method to study cell heterogeneity and for rare cell characterization. Despite the high cost and technical constraints, applications are increasing every year in all fields of biology. Following the trend, there is a tremendous development of tools for single-cell analysis, especially in the RNA sequencing field. Every improvement increases sensitivity and throughput. Collecting a large amount of data also stimulates the development of new approaches for bioinformatic analysis and interpretation. However, the essential requirement for any analysis is the collection of single cells of high quality. The single-cell isolation must be fast, effective, and gentle to maintain the native expression profiles. Classical methods for single-cell isolation are micromanipulation, microdissection, and fluorescence-activated cell sorting (FACS). In the last decade several new and highly efficient approaches have been developed, which not just supplement but may fully replace the traditional ones. These new techniques are based on microfluidic chips, droplets, micro-well plates, and automatic collection of cells using capillaries, magnets, an electric field, or a punching probe. In this review we summarize the current methods and developments in this field. We discuss the advantages of the different commercially available platforms and their applicability, and also provide remarks on future developments.

  6. Analysis of repeated measurement data in the clinical trials

    Science.gov (United States)

    Singh, Vineeta; Rana, Rakesh Kumar; Singhal, Richa

    2013-01-01

    Statistics is an integral part of Clinical Trials. Elements of statistics span Clinical Trial design, data monitoring, analyses and reporting. A solid understanding of statistical concepts by clinicians improves the comprehension and the resulting quality of Clinical Trials. In biomedical research it has been seen that researcher frequently use t-test and ANOVA to compare means between the groups of interest irrespective of the nature of the data. In Clinical Trials we record the data on the patients more than two times. In such a situation using the standard ANOVA procedures is not appropriate as it does not consider dependencies between observations within subjects in the analysis. To deal with such types of study data Repeated Measure ANOVA should be used. In this article the application of One-way Repeated Measure ANOVA has been demonstrated by using the software SPSS (Statistical Package for Social Sciences) Version 15.0 on the data collected at four time points 0 day, 15th day, 30th day, and 45th day of multicentre clinical trial conducted on Pandu Roga (~Iron Deficiency Anemia) with an Ayurvedic formulation Dhatrilauha. PMID:23930038

  7. Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial-rationale and study protocol.

    Science.gov (United States)

    Gaudino, Mario; Alexander, John H; Bakaeen, Faisal G; Ballman, Karla; Barili, Fabio; Calafiore, Antonio Maria; Davierwala, Piroze; Goldman, Steven; Kappetein, Peter; Lorusso, Roberto; Mylotte, Darren; Pagano, Domenico; Ruel, Marc; Schwann, Thomas; Suma, Hisayoshi; Taggart, David P; Tranbaugh, Robert F; Fremes, Stephen

    2017-12-01

    The primary hypothesis of the ROMA trial is that in patients undergoing primary isolated non-emergent coronary artery bypass grafting, the use of 2 or more arterial grafts compared with a single arterial graft (SAG) is associated with a reduction in the composite outcome of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization. The secondary hypothesis is that in these patients, the use of 2 or more arterial grafts compared with a SAG is associated with improved survival. The ROMA trial is a prospective, unblinded, randomized event-driven multicentre trial comprising at least 4300 subjects. Patients younger than 70 years with left main and/or multivessel disease will be randomized to a SAG or multiple arterial grafts to the left coronary system in a 1:1 fashion. Permuted block randomization stratified by the centre and the type of second arterial graft will be used. The primary outcome will be a composite of death from any cause, any stroke, post-discharge myocardial infarction and/or repeat revascularization. The secondary outcome will be all-cause mortality. The primary safety outcome will be a composite of death from any cause, any stroke and any myocardial infarction. In all patients, 1 internal thoracic artery will be anastomosed to the left anterior descending coronary artery. For patients randomized to the SAG group, saphenous vein grafts will be used for all non-left anterior descending target vessels. For patients randomized to the multiple arterial graft group, the main target vessel of the lateral wall will be grafted with either a radial artery or a second internal thoracic artery. Additional grafts for the multiple arterial graft group can be saphenous veins or supplemental arterial conduits. To detect a 20% relative reduction in the primary outcome, with 90% power at 5% alpha and assuming a time-to-event analysis, the sample size must include 845 events (and 3650 patients). To detect a 20% relative

  8. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

    International Nuclear Information System (INIS)

    Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

    1998-01-01

    Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. Sieve analysis in HIV-1 vaccine efficacy trials.

    Science.gov (United States)

    Edlefsen, Paul T; Gilbert, Peter B; Rolland, Morgane

    2013-09-01

    The genetic characterization of HIV-1 breakthrough infections in vaccine and placebo recipients offers new ways to assess vaccine efficacy trials. Statistical and sequence analysis methods provide opportunities to mine the mechanisms behind the effect of an HIV vaccine. The release of results from two HIV-1 vaccine efficacy trials, Step/HVTN-502 (HIV Vaccine Trials Network-502) and RV144, led to numerous studies in the last 5 years, including efforts to sequence HIV-1 breakthrough infections and compare viral characteristics between the vaccine and placebo groups. Novel genetic and statistical analysis methods uncovered features that distinguished founder viruses isolated from vaccinees from those isolated from placebo recipients, and identified HIV-1 genetic targets of vaccine-induced immune responses. Studies of HIV-1 breakthrough infections in vaccine efficacy trials can provide an independent confirmation to correlates of risk studies, as they take advantage of vaccine/placebo comparisons, whereas correlates of risk analyses are limited to vaccine recipients. Through the identification of viral determinants impacted by vaccine-mediated host immune responses, sieve analyses can shed light on potential mechanisms of vaccine protection.

  10. Attentional Selection in a Cocktail Party Environment Can Be Decoded from Single-Trial EEG

    Science.gov (United States)

    O'Sullivan, James A.; Power, Alan J.; Mesgarani, Nima; Rajaram, Siddharth; Foxe, John J.; Shinn-Cunningham, Barbara G.; Slaney, Malcolm; Shamma, Shihab A.; Lalor, Edmund C.

    2015-01-01

    How humans solve the cocktail party problem remains unknown. However, progress has been made recently thanks to the realization that cortical activity tracks the amplitude envelope of speech. This has led to the development of regression methods for studying the neurophysiology of continuous speech. One such method, known as stimulus-reconstruction, has been successfully utilized with cortical surface recordings and magnetoencephalography (MEG). However, the former is invasive and gives a relatively restricted view of processing along the auditory hierarchy, whereas the latter is expensive and rare. Thus it would be extremely useful for research in many populations if stimulus-reconstruction was effective using electroencephalography (EEG), a widely available and inexpensive technology. Here we show that single-trial (≈60 s) unaveraged EEG data can be decoded to determine attentional selection in a naturalistic multispeaker environment. Furthermore, we show a significant correlation between our EEG-based measure of attention and performance on a high-level attention task. In addition, by attempting to decode attention at individual latencies, we identify neural processing at ∼200 ms as being critical for solving the cocktail party problem. These findings open up new avenues for studying the ongoing dynamics of cognition using EEG and for developing effective and natural brain–computer interfaces. PMID:24429136

  11. Single-Trial Decoding of Bistable Perception Based on Sparse Nonnegative Tensor Decomposition

    Science.gov (United States)

    Wang, Zhisong; Maier, Alexander; Logothetis, Nikos K.; Liang, Hualou

    2008-01-01

    The study of the neuronal correlates of the spontaneous alternation in perception elicited by bistable visual stimuli is promising for understanding the mechanism of neural information processing and the neural basis of visual perception and perceptual decision-making. In this paper, we develop a sparse nonnegative tensor factorization-(NTF)-based method to extract features from the local field potential (LFP), collected from the middle temporal (MT) visual cortex in a macaque monkey, for decoding its bistable structure-from-motion (SFM) perception. We apply the feature extraction approach to the multichannel time-frequency representation of the intracortical LFP data. The advantages of the sparse NTF-based feature extraction approach lies in its capability to yield components common across the space, time, and frequency domains yet discriminative across different conditions without prior knowledge of the discriminating frequency bands and temporal windows for a specific subject. We employ the support vector machines (SVMs) classifier based on the features of the NTF components for single-trial decoding the reported perception. Our results suggest that although other bands also have certain discriminability, the gamma band feature carries the most discriminative information for bistable perception, and that imposing the sparseness constraints on the nonnegative tensor factorization improves extraction of this feature. PMID:18528515

  12. Role of multisensory stimuli in vigilance enhancement- a single trial event related potential study.

    Science.gov (United States)

    Abbasi, Nida Itrat; Bodala, Indu Prasad; Bezerianos, Anastasios; Yu Sun; Al-Nashash, Hasan; Thakor, Nitish V

    2017-07-01

    Development of interventions to prevent vigilance decrement has important applications in sensitive areas like transportation and defence. The objective of this work is to use multisensory (visual and haptic) stimuli for cognitive enhancement during mundane tasks. Two different epoch intervals representing sensory perception and motor response were analysed using minimum variance distortionless response (MVDR) based single trial ERP estimation to understand the performance dependency on both factors. Bereitschaftspotential (BP) latency L3 (r=0.6 in phase 1 (visual) and r=0.71 in phase 2 (visual and haptic)) was significantly correlated with reaction time as compared to that of sensory ERP latency L2 (r=0.1 in both phase 1 and phase 2). This implies that low performance in monotonous tasks is predominantly dependent on the prolonged neural interaction with the muscles to initiate movement. Further, negative relationship was found between the ERP latencies related to sensory perception and Bereitschaftspotential (BP) and occurrence of epochs when multisensory cues are provided. This means that vigilance decrement is reduced with the help of multisensory stimulus presentation in prolonged monotonous tasks.

  13. The application of particle filters in single trial event-related potential estimation

    International Nuclear Information System (INIS)

    Mohseni, Hamid R; Nazarpour, Kianoush; Sanei, Saeid; Wilding, Edward L

    2009-01-01

    In this paper, an approach for the estimation of single trial event-related potentials (ST-ERPs) using particle filters (PFs) is presented. The method is based on recursive Bayesian mean square estimation of ERP wavelet coefficients using their previous estimates as prior information. To enable a performance evaluation of the approach in the Gaussian and non-Gaussian distributed noise conditions, we added Gaussian white noise (GWN) and real electroencephalogram (EEG) signals recorded during rest to the simulated ERPs. The results were compared to that of the Kalman filtering (KF) approach demonstrating the robustness of the PF over the KF to the added GWN noise. The proposed method also outperforms the KF when the assumption about the Gaussianity of the noise is violated. We also applied this technique to real EEG potentials recorded in an odd-ball paradigm and investigated the correlation between the amplitude and the latency of the estimated ERP components. Unlike the KF method, for the PF there was a statistically significant negative correlation between amplitude and latency of the estimated ERPs, matching previous neurophysiological findings

  14. A single-blind trial of reflexology for irritable bowel syndrome.

    Science.gov (United States)

    Tovey, Philip

    2002-01-01

    BACKGROUND: Irritable bowel syndrome (IBS) is a significant problem for primary care, as treatment options are limited and it can frequently develop into a chronic condition. Complementary and alternative medicine, including reflexology, is being turned to increasingly in an attempt to manage symptoms. There are currently no studies which address the effectiveness of reflexology for IBS. Despite this, it continues to be advocated and used. AIM: To provide the first evidence on the effectiveness of reflexology in the management of the core defining symptoms of IBS. DESIGN OF STUDY: A single-blind trial carried out in primary care settings. SETTING: Thirty-four participants diagnosed with IBS on the basis of the Rome Criteria. METHOD: Participants were allocated to receive either a reflexology foot massage or a non-reflexology foot massage control group. RESULTS: On none of the three symptoms monitored--abdominal pain, constipation/diarrhoea, and abdominal distention--was there a statistically or clinically significant difference between reflexology and control groups. CONCLUSION: On the basis of these results there is nothing to suggest that reflexology produces any specific benefit for patients with IBS. There is currently no evidence to support its use. However this was one (relatively) small scale study; further research that, for example, assesses the impact of therapist (professional and lay) versus therapy, is still needed. PMID:11791811

  15. Single Layered Versus Double Layered Intestinal Anastomosis: A Randomized Controlled Trial

    Science.gov (United States)

    Mohapatra, Vandana; Singh, Surendra; Rath, Pratap Kumar; Behera, Tapas Ranjan

    2017-01-01

    Introduction Gastrointestinal anastomosis is one of the most common procedures being performed in oesophagogastric, hepatobiliary, bariatric, small bowel and colorectal surgery; however, the safety and efficacy of single layer or double layer anastomotic technique is still unclear. Aim To assess and compare the efficacy, safety and cost effectiveness of single layered versus double layered intestinal anastomosis. Materials and Methods This prospective, double-blind, randomized controlled comparative study comprised of patients who underwent intestinal resection and anastomosis. They were randomly assigned to undergo either single layered extra-mucosal anastomosis (Group-A) or double layered intestinal anastomosis (Group-B). Primary outcome measures included average time taken for anastomosis, postoperative complications, mean duration of hospital stay and cost of suture material used; secondary outcome measures assessed the postoperative return of bowel function. Statistical analysis was done by Chi-square test and student t-test. Results A total of 97 participants were randomized. Fifty patients were allocated to single layered extramucosal continuous anastomosis (Group-A) and 47 patients to double layered anastomosis (Group-B). The patients in each group were well matched for age, sex and diagnosis. The mean time taken for anastomosis (15.12±2.27 minutes in Group-A versus 24.38±2.26 minutes in Group-B) and the length of hospital stay (5.90±1.43 days in Group-A versus 7.29±1.89 days in Group-B) was significantly shorter in Group-A {p-value anastomosis. However, there was no significant difference in the complication rates between the two groups. Conclusion It can be concluded that single layered extramucosal continuous intestinal anastomosis is equally safe and perhaps more cost effective than the conventional double layered method and may represent the optimal choice for routine surgical practice. PMID:28764239

  16. Perceptive rehabilitation and trunk posture alignment in patients with Parkinson disease: a single blind randomized controlled trial.

    Science.gov (United States)

    Morrone, Michelangelo; Miccinilli, Sandra; Bravi, Marco; Paolucci, Teresa; Melgari, Jean M; Salomone, Gaetano; Picelli, Alessandro; Spadini, Ennio; Ranavolo, Alberto; Saraceni, Vincenzo M; DI Lazzaro, Vincenzo; Sterzi, Silvia

    2016-12-01

    Recent studies aimed to evaluate the potential effects of perceptive rehabilitation in Parkinson Disease reporting promising preliminary results for postural balance and pain symptoms. To date, no randomized controlled trial was carried out to compare the effects of perceptive rehabilitation and conventional treatment in patients with Parkinson Disease. To evaluate whether a perceptive rehabilitation treatment could be more effective than a conventional physical therapy program in improving postural control and gait pattern in patients with Parkinson Disease. Single blind, randomized controlled trial. Department of Physical and Rehabilitation Medicine of a University Hospital. Twenty outpatients affected by idiopathic Parkinson Disease at Hoehn and Yahr stage ≤3. Recruited patients were divided into two groups: the first one underwent individual treatment with Surfaces for Perceptive Rehabilitation (Su-Per), consisting of rigid wood surfaces supporting deformable latex cones of various dimensions, and the second one received conventional group physical therapy treatment. Each patient underwent a training program consisting of ten, 45-minute sessions, three days a week for 4 consecutive weeks. Each subject was evaluated before treatment, immediately after treatment and at one month of follow-up, by an optoelectronic stereophotogrammetric system for gait and posture analysis, and by a computerized platform for stabilometric assessment. Kyphosis angle decreased after ten sessions of perceptive rehabilitation, thus showing a substantial difference with respect to the control group. No significant differences were found as for gait parameters (cadence, gait speed and stride length) within Su-Per group and between groups. Parameters of static and dynamic evaluation on stabilometric platform failed to demonstrate any statistically relevant difference both within-groups and between-groups. Perceptive training may help patients affected by Parkinson Disease into restoring

  17. Single cell analysis contemporary research and clinical applications

    CERN Document Server

    Cossarizza, Andrea

    2017-01-01

    This book highlights the current state of the art in single cell analysis, an area that involves many fields of science – from clinical hematology, functional analysis and drug screening, to platelet and microparticle analysis, marine biology and fundamental cancer research. This book brings together an eclectic group of current applications, all of which have a significant impact on our current state of knowledge. The authors of these chapters are all pioneering researchers in the field of single cell analysis. The book will not only appeal to those readers more focused on clinical applications, but also those interested in highly technical aspects of the technologies. All of the technologies identified utilize unique applications of photon detection systems.

  18. Single-Molecule Analysis for RISC Assembly and Target Cleavage.

    Science.gov (United States)

    Sasaki, Hiroshi M; Tadakuma, Hisashi; Tomari, Yukihide

    2018-01-01

    RNA-induced silencing complex (RISC) is a small RNA-protein complex that mediates silencing of complementary target RNAs. Biochemistry has been successfully used to characterize the molecular mechanism of RISC assembly and function for nearly two decades. However, further dissection of intermediate states during the reactions has been warranted to fill in the gaps in our understanding of RNA silencing mechanisms. Single-molecule analysis with total internal reflection fluorescence (TIRF) microscopy is a powerful imaging-based approach to interrogate complex formation and dynamics at the individual molecule level with high sensitivity. Combining this technique with our recently established in vitro reconstitution system of fly Ago2-RISC, we have developed a single-molecule observation system for RISC assembly. In this chapter, we summarize the detailed protocol for single-molecule analysis of chaperone-assisted assembly of fly Ago2-RISC as well as its target cleavage reaction.

  19. Apparently conclusive meta-analyses may be inconclusive--Trial sequential analysis adjustment of random error risk due to repetitive testing of accumulating data in apparently conclusive neonatal meta-analyses

    DEFF Research Database (Denmark)

    Brok, Jesper; Thorlund, Kristian; Wetterslev, Jørn

    2008-01-01

    BACKGROUND: Random error may cause misleading evidence in meta-analyses. The required number of participants in a meta-analysis (i.e. information size) should be at least as large as an adequately powered single trial. Trial sequential analysis (TSA) may reduce risk of random errors due to repeti......BACKGROUND: Random error may cause misleading evidence in meta-analyses. The required number of participants in a meta-analysis (i.e. information size) should be at least as large as an adequately powered single trial. Trial sequential analysis (TSA) may reduce risk of random errors due...

  20. Analysis of single nucleotide polymorphisms in case-control studies.

    Science.gov (United States)

    Li, Yonghong; Shiffman, Dov; Oberbauer, Rainer

    2011-01-01

    Single nucleotide polymorphisms (SNPs) are the most common type of genetic variants in the human genome. SNPs are known to modify susceptibility to complex diseases. We describe and discuss methods used to identify SNPs associated with disease in case-control studies. An outline on study population selection, sample collection and genotyping platforms is presented, complemented by SNP selection, data preprocessing and analysis.

  1. Automatic settlement analysis of single-layer armour layers

    NARCIS (Netherlands)

    Hofland, B.; van gent, Marcel

    2016-01-01

    A method to quantify, analyse, and present the settlement of single-layer concrete armour layers of coastal structures is presented. The use of the image processing technique for settlement analysis is discussed based on various modelling
    studies performed over the years. The accuracy of the

  2. CrazyEgg Reports for Single Page Analysis

    Science.gov (United States)

    CrazyEgg provides an in depth look at visitor behavior on one page. While you can use GA to do trend analysis of your web area, CrazyEgg helps diagnose the design of a single Web page by visually displaying all visitor clicks during a specified time.

  3. Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial

  4. Intention-to-treat analysis in the chronic suppurative otitis media trials

    African Journals Online (AJOL)

    There were no attempts in any of the trials to impute for missing responses and carrying out a sensitivity analysis. For trials with a big percentage of protocol deviations, the validity of their results are brought to question. Conclusions: In practice, not all those entered into a randomised-controlled trial will complete the trial.

  5. Markov chain analysis of single spin flip Ising simulations

    International Nuclear Information System (INIS)

    Hennecke, M.

    1997-01-01

    The Markov processes defined by random and loop-based schemes for single spin flip attempts in Monte Carlo simulations of the 2D Ising model are investigated, by explicitly constructing their transition matrices. Their analysis reveals that loops over all lattice sites using a Metropolis-type single spin flip probability often do not define ergodic Markov chains, and have distorted dynamical properties even if they are ergodic. The transition matrices also enable a comparison of the dynamics of random versus loop spin selection and Glauber versus Metropolis probabilities

  6. Vibrational analysis of single-layered graphene sheets

    Energy Technology Data Exchange (ETDEWEB)

    Sakhaee-Pour, A; Ahmadian, M T [Center of Excellence in Design, Robotics and Automation (CEDRA), Department of Mechanical Engineering, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Naghdabadi, R [Department of Mechanical Engineering and Institute for Nano Science and Technology, Sharif University of Technology, Tehran (Iran, Islamic Republic of)], E-mail: sakhaee@alum.sharif.edu, E-mail: naghdabd@sharif.edu

    2008-02-27

    A molecular structural mechanics method has been implemented to investigate the vibrational behavior of single-layered graphene sheets. By adopting this approach, mode shapes and natural frequencies are obtained. Vibrational analysis is performed with different chirality and boundary conditions. Numerical results from the atomistic modeling are employed to develop predictive equations via a statistical nonlinear regression model. With the proposed equations, fundamental frequencies of single-layered graphene sheets with considered boundary conditions can be predicted within 3% difference with respect to the atomistic simulation.

  7. Immediate effects of kinesiotaping on quadriceps muscle strength: a single-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Vercelli, Stefano; Sartorio, Francesco; Foti, Calogero; Colletto, Lorenzo; Virton, Domenico; Ronconi, Gianpaolo; Ferriero, Giorgio

    2012-07-01

    To investigate the immediate effects on maximal muscle strength of kinesiotaping (KT) applied to the dominant quadriceps of healthy subjects. Single-blind, placebo-controlled crossover trial. "Salvatore Maugeri" Foundation. With ethical approval and informed consent, a convenience sample of 36 healthy volunteers were recruited. Two subjects did not complete the sessions and were excluded from the analysis. Subjects were tested across 3 different sessions, randomly receiving 2 experimental KT conditions applied with the aim of enhancing and inhibiting muscle strength and a sham KT application. Quadriceps muscle strength was measured by means of an isokinetic maximal test performed at 60 and 180 degrees per second. Two secondary outcome measures were performed: the single-leg triple hop for distance to measure limb performance and the Global Rating of Change Scale (GRCS) to calculate agreement between KT application and subjective perception of strength. Compared with baseline, none of the 3 taping conditions showed a significant change in muscle strength and performance (all P > 0.05). Effect size was very low under all conditions (≤0.08). Very few subjects showed an individual change greater than the minimal detectable change. Global Rating of Change Scale scores demonstrated low to moderate agreement with the type of KT applied, but some placebo effects were reported independently of condition. Our findings indicated no significant effect in the maximal quadriceps strength immediately after the application of inhibition, facilitation, or sham KT. These results do not support the use of KT applied in this way to change maximal muscle strength in healthy people.

  8. Application of modern tests for stationarity to single-trial MEG data: transferring powerful statistical tools from econometrics to neuroscience.

    Science.gov (United States)

    Kipiński, Lech; König, Reinhard; Sielużycki, Cezary; Kordecki, Wojciech

    2011-10-01

    Stationarity is a crucial yet rarely questioned assumption in the analysis of time series of magneto- (MEG) or electroencephalography (EEG). One key drawback of the commonly used tests for stationarity of encephalographic time series is the fact that conclusions on stationarity are only indirectly inferred either from the Gaussianity (e.g. the Shapiro-Wilk test or Kolmogorov-Smirnov test) or the randomness of the time series and the absence of trend using very simple time-series models (e.g. the sign and trend tests by Bendat and Piersol). We present a novel approach to the analysis of the stationarity of MEG and EEG time series by applying modern statistical methods which were specifically developed in econometrics to verify the hypothesis that a time series is stationary. We report our findings of the application of three different tests of stationarity--the Kwiatkowski-Phillips-Schmidt-Schin (KPSS) test for trend or mean stationarity, the Phillips-Perron (PP) test for the presence of a unit root and the White test for homoscedasticity--on an illustrative set of MEG data. For five stimulation sessions, we found already for short epochs of duration of 250 and 500 ms that, although the majority of the studied epochs of single MEG trials were usually mean-stationary (KPSS test and PP test), they were classified as nonstationary due to their heteroscedasticity (White test). We also observed that the presence of external auditory stimulation did not significantly affect the findings regarding the stationarity of the data. We conclude that the combination of these tests allows a refined analysis of the stationarity of MEG and EEG time series.

  9. Distance education and diabetes empowerment: A single-blind randomized control trial.

    Science.gov (United States)

    Zamanzadeh, Vahid; Zirak, Mohammad; Hemmati Maslakpak, Masomeh; Parizad, Naser

    2017-11-01

    Diabetes is one of the biggest problems in healthcare systems and kills many people every year. Diabetes management is impossible when only utilizing medication. So, patients must be educated to manage their diabetes. This study aims to assess the effect of education by telephone and short message service on empowering patients with type 2 diabetes (primary outcome). A single-blind randomized controlled trial was conducted in the Urmia diabetes association in Iran. Sixty six participants with definitive diagnosis of type 2 diabetes entered into the study. Patients with secondary health problems were excluded. Patients were selected by simple random sampling then allocated into intervention (n=33) and control (n=33) groups. The intervention group received an educational text message daily and instructive phone calls three days a week for three months along with usual care. The Diabetes Empowerment Scale (DES) with confirmed validity and reliability was used for collecting data. Data was analyzed using SPSS V6.1. Independent t-test, paired t-test and chi-square were used to analyze the data. The empowerment of the intervention group compared with the control group significantly improved after three months of distance education (p<0.00, EF=1. 16). The study findings show that the distance education has a significant effect on empowering patients with type 2 diabetes. Therefore, using distance education along with other diabetes management intervention is highly effective and should be part of the care in diabetes treatment. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  10. DNA analysis by single molecule stretching in nanofluidic biochips

    DEFF Research Database (Denmark)

    Abad, E.; Juarros, A.; Retolaza, A.

    2011-01-01

    Imprint Lithography (NIL) technology combined with a conventional anodic bonding of the silicon base and Pyrex cover. Using this chip, we have performed single molecule imaging on a bench-top fluorescent microscope system. Lambda phage DNA was used as a model sample to characterize the chip. Single molecules of λ-DNA......Stretching single DNA molecules by confinement in nanofluidic channels has attracted a great interest during the last few years as a DNA analysis tool. We have designed and fabricated a sealed micro/nanofluidic device for DNA stretching applications, based on the use of the high throughput Nano...... stained with the fluorescent dye YOYO-1 were stretched in the nanochannel array and the experimental results were analysed to determine the extension factor of the DNA in the chip and the geometrical average of the nanochannel inner diameter. The determination of the extension ratio of the chip provides...

  11. Enrichment Strategies in Pediatric Drug Development: An Analysis of Trials Submitted to the US Food and Drug Administration.

    Science.gov (United States)

    Green, Dionna J; Liu, Xiaomei I; Hua, Tianyi; Burnham, Janelle M; Schuck, Robert; Pacanowski, Michael; Yao, Lynne; McCune, Susan K; Burckart, Gilbert J; Zineh, Issam

    2017-12-08

    Clinical trial enrichment involves prospectively incorporating trial design elements that increase the probability of detecting a treatment effect. The use of enrichment strategies in pediatric drug development has not been systematically assessed. We analyzed the use of enrichment strategies in pediatric trials submitted to the US Food and Drug Administration from 2012-2016. In all, 112 efficacy studies associated with 76 drug development programs were assessed and their overall success rates were 78% and 75%, respectively. Eighty-eight trials (76.8%) employed at least one enrichment strategy; of these, 66.3% employed multiple enrichment strategies. The highest trial success rates were achieved when all three enrichment strategies (practical, predictive, and prognostic) were used together within a single trial (87.5%), while the lowest success rate was observed when no enrichment strategy was used (65.4%). The use of enrichment strategies in pediatric trials was found to be associated with trial and program success in our analysis. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  12. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  13. Outcomes with single-coil versus dual-coil implantable cardioverter defibrillators: a meta-analysis.

    Science.gov (United States)

    Sunderland, Nicholas; Kaura, Amit; Murgatroyd, Francis; Dhillon, Para; Scott, Paul A

    2018-03-01

    Dual-coil implantable cardioverter defibrillator (ICD) leads have traditionally been used over single-coil leads due to concerns regarding high defibrillation thresholds (DFT) and consequent poor shock efficacy. However, accumulating evidence suggests that this position may be unfounded and that dual-coil leads may also be associated with higher complication rates during lead extraction. This meta-analysis collates data comparing dual- and single-coil ICD leads. Electronic databases were systematically searched for randomized controlled trials (RCT) and non-randomized studies comparing single-coil and dual-coil leads. The mean differences in DFT and summary estimates of the odds-ratio (OR) for first-shock efficacy and the hazard-ratio (HR) for all-cause mortality were calculated using random effects models. Eighteen studies including a total of 138,124 patients were identified. Dual-coil leads were associated with a lower DFT compared to single coil leads (mean difference -0.83J; 95% confidence interval [CI] -1.39--0.27; P = 0.004). There was no difference in the first-shock success rate with dual-coil compared to single-coil leads (OR 0.74; 95%CI 0.45-1.21; P=0.22). There was a significantly lower risk of all-cause mortality associated with single-coil leads (HR 0.91; 95%CI 0.86-0.95; P dual-coil leads. The mortality benefit with single-coil leads most likely represents patient selection bias. Given the increased risk and complexity of extracting dual-coil leads, centres should strongly consider single-coil ICD leads as the lead of choice for routine new left-sided ICD implants. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  14. Impact of one-to-one tutoring on fundamentals of laparoscopic surgery (FLS) passing rate in a single center experience outside the United States: a randomized controlled trial.

    Science.gov (United States)

    Gheza, Federico; Raimondi, Paolo; Solaini, Leonardo; Coccolini, Federico; Baiocchi, Gian Luca; Portolani, Nazario; Tiberio, Guido Alberto Massimo

    2018-04-11

    Outside the US, FLS certification is not required and its teaching methods are not well standardized. Even if the FLS was designed as "stand alone" training system, most of Academic Institution offer support to residents during training. We present the first systematic application of FLS in Italy. Our aim was to evaluate the role of mentoring/coaching on FLS training in terms of the passing rate and global performance in the search for resource optimization. Sixty residents in general surgery, obstetrics & gynecology, and urology were selected to be enrolled in a randomized controlled trial, practicing FLS with the goal of passing a simulated final exam. The control group practiced exclusively with video material from SAGES, whereas the interventional group was supported by a mentor. Forty-six subjects met the requirements and completed the trial. For the other 14 subjects no results are available for comparison. One subject for each group failed the exam, resulting in a passing rate of 95.7%, with no obvious differences between groups. Subgroup analysis did not reveal any difference between the groups for FLS tasks. We confirm that methods other than video instruction and deliberate FLS practice are not essential to pass the final exam. Based on these results, we suggest the introduction of the FLS system even where a trained tutor is not available. This trial is the first single institution application of the FLS in Italy and one of the few experiences outside the US. Trial Number: NCT02486575 ( https://www.clinicaltrials.gov ).

  15. Single-cell regulome data analysis by SCRAT.

    Science.gov (United States)

    Ji, Zhicheng; Zhou, Weiqiang; Ji, Hongkai

    2017-09-15

    Emerging single-cell technologies (e.g. single-cell ATAC-seq, DNase-seq or ChIP-seq) have made it possible to assay regulome of individual cells. Single-cell regulome data are highly sparse and discrete. Analyzing such data is challenging. User-friendly software tools are still lacking. We present SCRAT, a Single-Cell Regulome Analysis Toolbox with a graphical user interface, for studying cell heterogeneity using single-cell regulome data. SCRAT can be used to conveniently summarize regulatory activities according to different features (e.g. gene sets, transcription factor binding motif sites, etc.). Using these features, users can identify cell subpopulations in a heterogeneous biological sample, infer cell identities of each subpopulation, and discover distinguishing features such as gene sets and transcription factors that show different activities among subpopulations. SCRAT is freely available at https://zhiji.shinyapps.io/scrat as an online web service and at https://github.com/zji90/SCRAT as an R package. hji@jhu.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  16. Scientist, Single Cell Analysis Facility | Center for Cancer Research

    Science.gov (United States)

    The Cancer Research Technology Program (CRTP) develops and implements emerging technology, cancer biology expertise and research capabilities to accomplish NCI research objectives.  The CRTP is an outward-facing, multi-disciplinary hub purposed to enable the external cancer research community and provides dedicated support to NCI’s intramural Center for Cancer Research (CCR).  The dedicated units provide electron microscopy, protein characterization, protein expression, optical microscopy and nextGen sequencing. These research efforts are an integral part of CCR at the Frederick National Laboratory for Cancer Research (FNLCR).  CRTP scientists also work collaboratively with intramural NCI investigators to provide research technologies and expertise. KEY ROLES AND RESPONSIBILITIES We are seeking a highly motivated Scientist II to join the newly established Single Cell Analysis Facility (SCAF) of the Center for Cancer Research (CCR) at NCI. The SCAF will house state of the art single cell sequencing technologies including 10xGenomics Chromium, BD Genomics Rhapsody, DEPPArray, and other emerging single cell technologies. The Scientist: Will interact with close to 200 laboratories within the CCR to design and carry out single cell experiments for cancer research Will work on single cell isolation/preparation from various tissues and cells and related NexGen sequencing library preparation Is expected to author publications in peer reviewed scientific journals

  17. Single-trial regression elucidates the role of prefrontal theta oscillations in response conflict

    NARCIS (Netherlands)

    Cohen, M.X.; Cavanagh, J.F.

    2011-01-01

    In most cognitive neuroscience experiments there are many behavioral and experimental dynamics, and many indices of brain activity, that vary from trial to trial. For example, in studies of response conflict, conflict is usually treated as a binary variable (i.e., response conflict exists or does

  18. Relay model for recruiting alcohol dependent patients in general hospitals--a single-blind pragmatic randomized trial

    DEFF Research Database (Denmark)

    Schwarz, Anne-Sophie; Bilberg, Randi; Bjerregaard, Lene Berit Skov

    2016-01-01

    - The Relay Model. METHOD/DESIGN: The study is a single-blind pragmatic randomized controlled trial including patients admitted to the hospital. The study group (n = 500) will receive an intervention, and the control group (n = 500) will be referred to treatment by usual procedures. All patients complete......://register.clinicaltrials.gov/by identifier: RESCueH_Relay NCT02188043 Project Relay Model for Recruiting Alcohol Dependent Patients in General Hospitals (TRN Registration: 07/09/2014)....

  19. Thermogravimetric Analysis of Single-Wall Carbon Nanotubes

    Science.gov (United States)

    Arepalli, Sivram; Nikolaev, Pavel; Gorelik, Olga

    2010-01-01

    An improved protocol for thermogravimetric analysis (TGA) of samples of single-wall carbon nanotube (SWCNT) material has been developed to increase the degree of consistency among results so that meaningful comparisons can be made among different samples. This improved TGA protocol is suitable for incorporation into the protocol for characterization of carbon nanotube material. In most cases, TGA of carbon nanotube materials is performed in gas mixtures that contain oxygen at various concentrations. The improved protocol is summarized.

  20. Optimized variational analysis scheme of single Doppler radar wind data

    Science.gov (United States)

    Sasaki, Yoshi K.; Allen, Steve; Mizuno, Koki; Whitehead, Victor; Wilk, Kenneth E.

    1989-01-01

    A computer scheme for extracting singularities has been developed and applied to single Doppler radar wind data. The scheme is planned for use in real-time wind and singularity analysis and forecasting. The method, known as Doppler Operational Variational Extraction of Singularities is outlined, focusing on the principle of local symmetry. Results are presented from the application of the scheme to a storm-generated gust front in Oklahoma on May 28, 1987.

  1. Forest Analysis by Single-Pass Millimeterwave SAR Tomography

    OpenAIRE

    Schmitt, Michael; Zhu, Xiao Xiang

    2016-01-01

    Recent investigations show that millimeterwave SAR tomography provides an interesting means for the analysis of forested areas, especially if single-pass systems are employed. Providing very high resolutions in the decimeter domain and highly coherent data also for slightly windy conditions, even individual trees can be considered. Besides, it has been shown that a certain amount of canopy penetration is possible in spite of the short wavelength.

  2. Single-Family Energy Auditor Job Task Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Head, Heather R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurnik, Charles W [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-05-02

    The National Renewable Energy Laboratory (NREL) is contracted by the U.S. Department of Energy (DOE) Weatherization Assistance Program (WAP) to develop and maintain the resources under the Guidelines for Home Energy Professionals (GHEP) project. As part of the GHEP strategy to increase the quality of work conducted for single-family, residential energy-efficiency retrofits, the Home Energy Professionals Job Task Analysis are used as the foundation for quality training programs and trainers.

  3. Can teaching research methodology influence students' attitude toward science? Cohort study and nonrandomized trial in a single medical school.

    Science.gov (United States)

    Vujaklija, Ana; Hren, Darko; Sambunjak, Dario; Vodopivec, Ivana; Ivanis, Ana; Marusić, Ana; Marusić, Matko

    2010-02-01

    Medical teaching aims to develop attitudes and behaviors underlying professional competence of future physicians. We investigated whether a mandatory course on scientific methodology in the second study year could affect students' attitudes toward science in medicine. In a longitudinal study, students (n = 241) enrolling in 2001-2002 academic year at a single medical school were followed up until graduation in 2006-2007. Each year, they filled out a Likert-type questionnaire of 18 statements evaluating attitude toward science. Direct influence of the course on students' attitudes was tested in a nonrandomized controlled trial with the 2006-2007 second year student cohort. Positive students' attitudes toward science increased during study years (mean [SD] score of the maximum score of 90): from 57.6 (6.0) in the first to 69.8 (10.4) in the sixth year. There was a significant trend of increase in attitudes with the years of study (cubic trend by polynomial contrasts analysis, P = 0.011). Attendance of a course on research methodology significantly increased positive attitudes (score, 67.0 [7.0] before and 70.8 [7.5] after course, P = 0.032 vs control group), regardless of grade point average. The intervention had an effect even when the influence of the initial attitude was accounted for (F1,140 = 9.25, P = 0.003; analysis of covariance). The attitude changes after the course was greatest in students with low initial attitude scores (Spearman rinitial score, score difference, -0.44). Medical students have positive attitudes toward science and scientific method in medicine. Attendance of a course on research methodology had positive short-term effect on students' attitudes toward science. This positive effect should be maintained by vertical integration of the course in the medical curriculum.

  4. Precise analysis of the metal package photomultiplier single photoelectron spectra

    International Nuclear Information System (INIS)

    Chirikov-Zorin, I.E.; Fedorko, I.; Sykora, I.; Tokar, S.; Menzione, A.

    2000-01-01

    A deconvolution method based on a sophisticated photomultiplier response function was used to analyse the compact metal package photomultiplier spectra taken in single photoelectron mode. The spectra taken by Hamamtsu R5600 and R5900 photomultipliers have been analysed. The detailed analysis shows that the method appropriately describes the process of charge multiplication in these photomultipliers in a wide range of working regimes and the deconvoluted parameters are established with about 1% accuracy. The method can be used for a detailed analysis of photomultiplier noise and for calibration purposes

  5. The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: Results from the FACS trial.

    Directory of Open Access Journals (Sweden)

    Bethany Shinkins

    Full Text Available To evaluate the diagnostic accuracy of a single CEA (carcinoembryonic antigen blood test in detecting colorectal cancer recurrence.Patients who have undergone curative resection for primary colorectal cancer are typically followed up with scheduled CEA testing for 5 years. Decisions to investigate further (usually by CT imaging are based on single test results, reflecting international guidelines.A secondary analysis was undertaken of data from the FACS trial (two arms included CEA testing. The composite reference standard applied included CT-CAP imaging, clinical assessment and colonoscopy. Accuracy in detecting recurrence was evaluated in terms of sensitivity, specificity, likelihood ratios, predictive values, time-dependent area under the ROC curves, and operational performance when used prospectively in clinical practice are reported.Of 582 patients, 104 (17.9% developed recurrence during the 5 year follow-up period. Applying the recommended threshold of 5μg/L achieves at best 50.0% sensitivity (95% CI: 40.1-59.9%; in prospective use in clinical practice it would lead to 56 missed recurrences (53.8%; 95% CI: 44.2-64.4% and 89 false alarms (56.7% of 157 patients referred for investigation. Applying a lower threshold of 2.5μg/L would reduce the number of missed recurrences to 36.5% (95% CI: 26.5-46.5% but would increase the false alarms to 84.2% (924/1097 referred. Some patients are more prone to false alarms than others-at the 5μg/L threshold, the 89 episodes of unnecessary investigation were clustered in 29 individuals.Our results demonstrated very low sensitivity for CEA, bringing to question whether it could ever be used as an independent triage test. It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated. Current national and international guidelines merit re-evaluation and options to improve performance, such as

  6. Operational trials of single- and multi-element CR-39 dosemeters for the DIDO and PLUTO reactors at the Harwell Laboratory

    International Nuclear Information System (INIS)

    Gallacher, G.G.; Perks, C.A.

    1993-01-01

    Single- and multi-element CR-39 dosemeters, developed at the Harwell Laboratory, and a commercially available multi-element CR-39 dosemeter (obtained from Track Analysis Systems Ltd), were evaluated for their potential as neutron dosemeters for personnel working at Harwell Laboratory's research reactors. Owing to the angular dependence of the CR-39 (processed using electrochemical etching), the single-element dosemeter was found to be impractical. Consequently, a multi-element dosemeter was developed, which consisted of a cube of side 36 mm with CR-39 elements (also processed using electrochemical etching) attached to each of the sides. Although this dosemeter was technically suitable for this type of dosimetry, it was considered to be unacceptably bulky in personnel trials. The commercially available CR-39 dosemeter tested was much smaller (the CR-39 was only chemically etched) and this was considered to be acceptable as a personnel dosemeter. In addition, trials with personnel working at active handling glove boxes indicated that single-element dosemeters might be adequate, but further work would be needed to verify this. (author)

  7. Efficacy of paraffin bath therapy in hand osteoarthritis: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Dilek, Banu; Gözüm, Mehtap; Şahin, Ebru; Baydar, Meltem; Ergör, Gül; El, Ozlem; Bircan, Çigdem; Gülbahar, Selmin

    2013-04-01

    To evaluate the efficacy of paraffin bath therapy on pain, function, and muscle strength in patients with hand osteoarthritis. Prospective single-blinded randomized controlled trial. Department of physical medicine and rehabilitation in a university hospital. Patients with bilateral hand osteoarthritis (N=56). Patients were randomized into 2 groups with a random number table by using block randomization with 4 patients in a block. Group 1 (n=29) had paraffin bath therapy (5 times per week, for 3-week duration) for both hands. Group 2 (n=27) was the control group. All patients were informed about joint-protection techniques, and paracetamol intake was recorded. The primary outcome measures were pain (at last 48h) at rest and during activities of daily living (ADL), assessed with a visual analog scale (0-10cm) at 12 weeks. The secondary outcome measures were the Australian Canadian Osteoarthritis Hand Index (AUSCAN) and the Dreiser Functional Index (DFI), used for subjective functional evaluation, loss of range of motion (ROM), grip and pinch strength, painful and tender joint counts, and paracetamol intake. A researcher blind to group allocation recorded the measures for both hands at baseline, 3 weeks, and 12 weeks at the hospital setting. At baseline, there were no significant differences between groups in any of the parameters (P>.05). After treatment, the paraffin group exhibited significant improvement in pain at rest and during ADL, ROM of the right hand, and pain and stiffness dimensions of the AUSCAN (P.05). The control group showed a significant deterioration in right hand grip and bilateral lateral pinch and right chuck pinch strength (Pparaffin group (Pparaffin group were significantly higher than the control group at 12 weeks (PParaffin bath therapy seemed to be effective both in reducing pain and tenderness and maintaining muscle strength in hand osteoarthritis. It may be regarded as a beneficial short-term therapy option, which is effective for a 12

  8. Signal Integrity Analysis in Single and Bundled Carbon Nanotube Interconnects

    International Nuclear Information System (INIS)

    Majumder, M.K.; Pandya, N.D.; Kaushik, B.K.; Manhas, S.K.

    2013-01-01

    Carbon nanotube (CN T) can be considered as an emerging interconnect material in current nano scale regime. They are more promising than other interconnect materials such as Al or Cu because of their robustness to electromigration. This research paper aims to address the crosstalk-related issues (signal integrity) in interconnect lines. Different analytical models of single- (SWCNT), double- (DWCNT), and multiwalled CNTs (MWCNT) are studied to analyze the crosstalk delay at global interconnect lengths. A capacitively coupled three-line bus architecture employing CMOS driver is used for accurate estimation of crosstalk delay. Each line in bus architecture is represented with the equivalent RLC models of single and bundled SWCNT, DWCNT, and MWCNT interconnects. Crosstalk delay is observed at middle line (victim) when it switches in opposite direction with respect to the other two lines (aggressors). Using the data predicted by ITRS 2012, a comparative analysis on the basis of crosstalk delay is performed for bundled SWCNT/DWCNT and single MWCNT interconnects. It is observed that the overall crosstalk delay is improved by 40.92% and 21.37% for single MWCNT in comparison to bundled SWCNT and bundled DWCNT interconnects, respectively.

  9. Process analysis in a THTR trial reprocessing plant

    International Nuclear Information System (INIS)

    Brodda, B.G.; Filss, P.; Kirchner, H.; Kroth, K.; Lammertz, H.; Schaedlich, W.; Brocke, W.; Buerger, K.; Halling, H.; Watzlawik, K.H.

    1979-01-01

    The demands on an analytical control system for a THTR trial reprocessing plant are specified. In a rather detailed example, a typical sampling, sample monitoring and measuring process is described. Analytical control is partly automated. Data acquisition and evaluation by computer are described for some important, largely automated processes. Sample management and recording of in-line and off-line data are carried out by a data processing system. Some important experiments on sample taking, sample transport and on special analysis are described. (RB) [de

  10. Extractables analysis of single-use flexible plastic biocontainers.

    Science.gov (United States)

    Marghitoiu, Liliana; Liu, Jian; Lee, Hans; Perez, Lourdes; Fujimori, Kiyoshi; Ronk, Michael; Hammond, Matthew R; Nunn, Heather; Lower, Asher; Rogers, Gary; Nashed-Samuel, Yasser

    2015-01-01

    Studies of the extractable profiles of bioprocessing components have become an integral part of drug development efforts to minimize possible compromise in process performance, decrease in drug product quality, and potential safety risk to patients due to the possibility of small molecules leaching out from the components. In this study, an effective extraction solvent system was developed to evaluate the organic extractable profiles of single-use bioprocess equipment, which has been gaining increasing popularity in the biopharmaceutical industry because of the many advantages over the traditional stainless steel-based bioreactors and other fluid mixing and storage vessels. The chosen extraction conditions were intended to represent aggressive conditions relative to the application of single-use bags in biopharmaceutical manufacture, in which aqueous based systems are largely utilized. Those extraction conditions, along with a non-targeted analytical strategy, allowed for the generation and identification of an array of extractable compounds; a total of 53 organic compounds were identified from four types of commercially available single-use bags, the majority of which are degradation products of polymer additives. The success of this overall extractables analysis strategy was reflected partially by the effectiveness in the extraction and identification of a compound that was later found to be highly detrimental to mammalian cell growth. The usage of single-use bioreactors has been increasing in biopharmaceutical industry because of the appealing advantages that it promises regarding to the cleaning, sterilization, operational flexibility, and so on, during manufacturing of biologics. However, compared to its conventional counterparts based mainly on stainless steel, single-use bioreactors are more susceptible to potential problems associated with compound leaching into the bioprocessing fluid. As a result, extractable profiling of the single-use system has become

  11. Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

    International Nuclear Information System (INIS)

    Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

    2017-01-01

    Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

  12. Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

    Energy Technology Data Exchange (ETDEWEB)

    Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Zhang, Jianjun [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Lin, Steven H. [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2017-03-15

    Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.

  13. Single Point Vulnerability Analysis of Automatic Seismic Trip System

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Seo Bin; Chung, Soon Il; Lee, Yong Suk [FNC Technology Co., Yongin (Korea, Republic of); Choi, Byung Pil [KHNP CRI, Daejeon (Korea, Republic of)

    2016-10-15

    Single Point Vulnerability (SPV) analysis is a process used to identify individual equipment whose failure alone will result in a reactor trip, turbine generator failure, or power reduction of more than 50%. Automatic Seismic Trip System (ASTS) is a newly installed system to ensure the safety of plant when earthquake occurs. Since this system directly shuts down the reactor, the failure or malfunction of its system component can cause a reactor trip more frequently than other systems. Therefore, an SPV analysis of ASTS is necessary to maintain its essential performance. To analyze SPV for ASTS, failure mode and effect analysis (FMEA) and fault tree analysis (FTA) was performed. In this study, FMEA and FTA methods were performed to select SPV equipment of ASTS. D/O, D/I, A/I card, seismic sensor, and trip relay had an effect on the reactor trip but their single failure will not cause reactor trip. In conclusion, ASTS is excluded as SPV. These results can be utilized as the basis data for ways to enhance facility reliability such as design modification and improvement of preventive maintenance procedure.

  14. Single Point Vulnerability Analysis of Automatic Seismic Trip System

    International Nuclear Information System (INIS)

    Oh, Seo Bin; Chung, Soon Il; Lee, Yong Suk; Choi, Byung Pil

    2016-01-01

    Single Point Vulnerability (SPV) analysis is a process used to identify individual equipment whose failure alone will result in a reactor trip, turbine generator failure, or power reduction of more than 50%. Automatic Seismic Trip System (ASTS) is a newly installed system to ensure the safety of plant when earthquake occurs. Since this system directly shuts down the reactor, the failure or malfunction of its system component can cause a reactor trip more frequently than other systems. Therefore, an SPV analysis of ASTS is necessary to maintain its essential performance. To analyze SPV for ASTS, failure mode and effect analysis (FMEA) and fault tree analysis (FTA) was performed. In this study, FMEA and FTA methods were performed to select SPV equipment of ASTS. D/O, D/I, A/I card, seismic sensor, and trip relay had an effect on the reactor trip but their single failure will not cause reactor trip. In conclusion, ASTS is excluded as SPV. These results can be utilized as the basis data for ways to enhance facility reliability such as design modification and improvement of preventive maintenance procedure

  15. SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

    NARCIS (Netherlands)

    BIJL, W; JANKNEGT, RA

    1993-01-01

    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5

  16. Taking into account latency, amplitude, and morphology: improved estimation of single-trial ERPs by wavelet filtering and multiple linear regression.

    Science.gov (United States)

    Hu, L; Liang, M; Mouraux, A; Wise, R G; Hu, Y; Iannetti, G D

    2011-12-01

    Across-trial averaging is a widely used approach to enhance the signal-to-noise ratio (SNR) of event-related potentials (ERPs). However, across-trial variability of ERP latency and amplitude may contain physiologically relevant information that is lost by across-trial averaging. Hence, we aimed to develop a novel method that uses 1) wavelet filtering (WF) to enhance the SNR of ERPs and 2) a multiple linear regression with a dispersion term (MLR(d)) that takes into account shape distortions to estimate the single-trial latency and amplitude of ERP peaks. Using simulated ERP data sets containing different levels of noise, we provide evidence that, compared with other approaches, the proposed WF+MLR(d) method yields the most accurate estimate of single-trial ERP features. When applied to a real laser-evoked potential data set, the WF+MLR(d) approach provides reliable estimation of single-trial latency, amplitude, and morphology of ERPs and thereby allows performing meaningful correlations at single-trial level. We obtained three main findings. First, WF significantly enhances the SNR of single-trial ERPs. Second, MLR(d) effectively captures and measures the variability in the morphology of single-trial ERPs, thus providing an accurate and unbiased estimate of their peak latency and amplitude. Third, intensity of pain perception significantly correlates with the single-trial estimates of N2 and P2 amplitude. These results indicate that WF+MLR(d) can be used to explore the dynamics between different ERP features, behavioral variables, and other neuroimaging measures of brain activity, thus providing new insights into the functional significance of the different brain processes underlying the brain responses to sensory stimuli.

  17. Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

    Directory of Open Access Journals (Sweden)

    Joseph S Ross

    2009-09-01

    Full Text Available ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515, nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46% of trials were published, among which 96 (31% provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357 were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001, but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22. Among trials that reported an end date, 75 of 123 (61% completed prior to 2004, 50 of 96 (52% completed during 2004, and 62 of 149 (42% completed during 2005 were published (p = 0.006.Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data

  18. Mission analysis report for single-shell tank leakage mitigation

    International Nuclear Information System (INIS)

    Cruse, J.M.

    1994-01-01

    This document provides an analysis of the leakage mitigation mission applicable to past and potential future leakage from the Hanford Site's 149 single-shell high-level waste tanks. This mission is a part of the overall missions of the Westinghouse Hanford Company Tank Waste Remediation System division to remediate the tank waste in a safe and acceptable manner. Systems engineers principles are being applied to this effort. Mission analysis supports early decision making by clearly defining program objectives. This documents identifies the initial conditions and acceptable final conditions, defines the programmatic and physical interfaces and constraints, estimates the resources to carry out the mission, and establishes measures of success. The results of the mission analysis provide a consistent basis for subsequent systems engineering work

  19. Emotion Recognition from Single-Trial EEG Based on Kernel Fisher’s Emotion Pattern and Imbalanced Quasiconformal Kernel Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Yi-Hung Liu

    2014-07-01

    Full Text Available Electroencephalogram-based emotion recognition (EEG-ER has received increasing attention in the fields of health care, affective computing, and brain-computer interface (BCI. However, satisfactory ER performance within a bi-dimensional and non-discrete emotional space using single-trial EEG data remains a challenging task. To address this issue, we propose a three-layer scheme for single-trial EEG-ER. In the first layer, a set of spectral powers of different EEG frequency bands are extracted from multi-channel single-trial EEG signals. In the second layer, the kernel Fisher’s discriminant analysis method is applied to further extract features with better discrimination ability from the EEG spectral powers. The feature vector produced by layer 2 is called a kernel Fisher’s emotion pattern (KFEP, and is sent into layer 3 for further classification where the proposed imbalanced quasiconformal kernel support vector machine (IQK-SVM serves as the emotion classifier. The outputs of the three layer EEG-ER system include labels of emotional valence and arousal. Furthermore, to collect effective training and testing datasets for the current EEG-ER system, we also use an emotion-induction paradigm in which a set of pictures selected from the International Affective Picture System (IAPS are employed as emotion induction stimuli. The performance of the proposed three-layer solution is compared with that of other EEG spectral power-based features and emotion classifiers. Results on 10 healthy participants indicate that the proposed KFEP feature performs better than other spectral power features, and IQK-SVM outperforms traditional SVM in terms of the EEG-ER accuracy. Our findings also show that the proposed EEG-ER scheme achieves the highest classification accuracies of valence (82.68% and arousal (84.79% among all testing methods.

  20. Increased reaction time variability in attention-deficit hyperactivity disorder as a response-related phenomenon: evidence from single-trial event-related potentials.

    Science.gov (United States)

    Saville, Christopher W N; Feige, Bernd; Kluckert, Christian; Bender, Stephan; Biscaldi, Monica; Berger, Andrea; Fleischhaker, Christian; Henighausen, Klaus; Klein, Christoph

    2015-07-01

    Increased intra-subject variability (ISV) in reaction times (RTs) is a promising endophenotype for attention-deficit hyperactivity disorder (ADHD) and among the most robust hallmarks of the disorder. ISV has been assumed to represent an attentional deficit, either reflecting lapses in attention or increased neural noise. Here, we use an innovative single-trial event-related potential approach to assess whether the increased ISV associated with ADHD is indeed attributable to attention, or whether it is related to response-related processing. We measured electroencephalographic responses to working memory oddball tasks in patients with ADHD (N = 20, aged 11.3 ± 1.1) and healthy controls (N = 25, aged 11.7 ± 1.1), and analysed these data with a recently developed method of single-trial event-related potential analysis. Estimates of component latency variability were computed for the stimulus-locked and response-locked forms of the P3b and the lateralised readiness potential (LRP). ADHD patients showed significantly increased ISV in behavioural ISV. This increased ISV was paralleled by an increase in variability in response-locked event-related potential latencies, while variability in stimulus-locked latencies was equivalent between groups. This result held across the P3b and LRP. Latency of all components predicted RTs on a single-trial basis, confirming that all were relevant for speed of processing. These data suggest that the increased ISV found in ADHD could be associated with response-end, rather than stimulus-end processes, in contrast to prevailing conceptions about the endophenotype. This mental chronometric approach may also be useful for exploring whether the existing lack of specificity of ISV to particular psychiatric conditions can be improved upon. © 2014 Association for Child and Adolescent Mental Health.

  1. Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials.

    Science.gov (United States)

    Leite, Elton T T; Moraes, Fabio Y; Marta, Gustavo N; Taunk, Neil K; Vieira, Marina T L; Hanna, Samir A; Silva, João Luis F; Carvalho, Heloisa A

    2017-06-01

    We aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. We searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). 1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. nPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses

    DEFF Research Database (Denmark)

    Brok, J.; Thorlund, K.; Gluud, C.

    2008-01-01

    in 80% (insufficient information size). TSA(15%) and TSA(LBHIS) found that 95% and 91% had absence of evidence. The remaining nonsignificant meta-analyses had evidence of lack of effect. CONCLUSION: TSA reveals insufficient information size and potentially false positive results in many meta......OBJECTIVES: To evaluate meta-analyses with trial sequential analysis (TSA). TSA adjusts for random error risk and provides the required number of participants (information size) in a meta-analysis. Meta-analyses not reaching information size are analyzed with trial sequential monitoring boundaries...... analogous to interim monitoring boundaries in a single trial. STUDY DESIGN AND SETTING: We applied TSA on meta-analyses performed in Cochrane Neonatal reviews. We calculated information sizes and monitoring boundaries with three different anticipated intervention effects of 30% relative risk reduction (TSA...

  3. General practice-based clinical trials in Germany - a problem analysis

    Directory of Open Access Journals (Sweden)

    Hummers-Pradier Eva

    2012-11-01

    Full Text Available Abstract Background In Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy. Methods Based on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented. Results In Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1 problem analysis, and definition of (2 structural prerequisites and (3 procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs, templates, checklists and other supporting materials for researchers. Conclusion All in all, our problem analyses revealed that

  4. Cortical activities of single-trial P300 amplitudes modulated by memory load using simultaneous EEG-fMRI

    Science.gov (United States)

    Zhang, Qiushi; Zhao, Xiaojie; Zhu, Chaozhe; Yang, Xueqian; Yao, Li

    2015-03-01

    The functional magnetic resonance imaging (fMRI) researches on working memory have found that activation of cortical areas appeared dependent on memory load, and event-related potentials (ERP) studies have demonstrated that amplitudes of P300 decreased significantly when working memory load increased. However, the cortical activities related with P300 amplitudes under different memory loads remains unclear. Joint fMRI and EEG analysis which fusions the time and spatial information in simultaneous EEG-fMRI recording can reveal the regional activation at each ERP time point. In this paper, we first used wavelet transform to obtain the single-trial amplitudes of P300 caused by a digital N-back task in the simultaneous EEG-fMRI recording as the ERP feature sequences. Then the feature sequences in 1-back condition and 3-back condition were introduced into general linear model (GLM) separately as parametric modulations to compare the cortical activation under different memory loads. The results showed that the average amplitudes of P300 in 3-back significantly decreased than that in 1-back, and the activities induced by ERP feature sequences in 3-back also significantly decreased than that in the 1-back, including the insular, anterior cingulate cortex, right inferior frontal gyrus, and medial frontal gyrus, which were relevant to the storage, monitoring, and manipulation of information in working memory task. Moreover, the difference in the activation caused by ERP feature showed a positive correlation with the difference in behavioral performance. These findings demonstrated the locations of P300 amplitudes differences modulated by the memory load and its relationship with the behavioral performance.

  5. Estimating outcomes and cost effectiveness using a single-arm clinical trial: ofatumumab for double-refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Hatswell, Anthony J; Thompson, Gwilym J; Maroudas, Penny A; Sofrygin, Oleg; Delea, Thomas E

    2017-01-01

    Ofatumumab (Arzerra ® , Novartis) is a treatment for chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab [double refractory (DR-CLL)]. Ofatumumab was licensed on the basis of an uncontrolled Phase II study, Hx-CD20-406, in which patients receiving ofatumumab survived for a median of 13.9 months. However, the lack of an internal control arm presents an obstacle for the estimation of comparative effectiveness. The objective of the study was to present a method to estimate the cost effectiveness of ofatumumab in the treatment of DR-CLL. As no suitable historical control was available for modelling, the outcomes from non-responders to ofatumumab were used to model the effect of best supportive care (BSC). This was done via a Cox regression to control for differences in baseline characteristics between groups. This analysis was included in a partitioned survival model built in Microsoft ® Excel with utilities and costs taken from published sources, with costs and quality-adjusted life years (QALYs) were discounted at a rate of 3.5% per annum. Using the outcomes seen in non-responders, ofatumumab is expected to add approximately 0.62 life years (1.50 vs. 0.88). Using published utility values this translates to an additional 0.30 QALYs (0.77 vs. 0.47). At the list price, ofatumumab had a cost per QALY of £130,563, and a cost per life year of £63,542. The model was sensitive to changes in assumptions regarding overall survival estimates and utility values. This study demonstrates the potential of using data for non-responders to model outcomes for BSC in cost-effectiveness evaluations based on single-arm trials. Further research is needed on the estimation of comparative effectiveness using uncontrolled clinical studies.

  6. Comparison of Effectiveness of Reflexology and Abdominal Massage on Constipation among Orthopedic Patients: A single-blind Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Alehe Seyyedrassoli

    2016-10-01

    Full Text Available Constipation is one of the most common health problems presenting in patients hospitalized within orthopedic settings. This present study was done with the aim of determining the effect of foot reflexology and abdominal massage on constipation severity. This study is a single -blind randomized controlled trial completed using 3 groups comprising a total of 60 patients hospitalized in the orthopedic wards of shohada hospital in the Northwest Azerbaijan- Iran. One of the intervention groups involved the use of foot reflexology and in the other abdominal massage was carried out once daily for 6 days. An assessor blinded to the group allocation measured and recorded constipation severity before the intervention, then daily from day 1 until day 6 post intervention by constipation evaluation scale. For data analysis, ANOVA, ANCOVA and repeated measurement ANOVA tests was used in SPSS version 16. There was no significant difference between the intervention and control groups in constipation severity over the first two days (p>0. 05 built from the 3rd until the 6th days after the intervention, the difference was significant (p0.05. After modification and deleting covariate variables, again, there was a significant difference between intervention groups with a control group from day 3 until day 6 of the intervention(p<0. 05, (effect size from 34% to 50%. Time had a significant effect on constipation severity reduction during the study, meaning that constipation, severe in the intervention groups decreased significantly as the study progressed (p<0. 05. The positive effects of foot reflexology and abdominal massage on the severity of constipation in hospitalized patients means that both can be used as economical and noninvasive nursing interventions for the relief of constipation.

  7. Analysis of opioid consumption in clinical trials: a simulation based analysis of power of four approaches

    DEFF Research Database (Denmark)

    Juul, Rasmus Vestergaard; Nyberg, Joakim; Kreilgaard, Mads

    2017-01-01

    Inconsistent trial design and analysis is a key reason that few advances in postoperative pain management have been made from clinical trials analyzing opioid consumption data. This study aimed to compare four different approaches to analyze opioid consumption data. A repeated time-to-event (RTTE...... to determine sample size required to demonstrate efficacy with 80% power using t test, Mann-Whitney rank sum test, time-to-event (TTE) modeling and RTTE modeling. Precision of efficacy estimates for RTTE models were evaluated in 500 simulations. A sample size of 50 patients was required to detect 37% morphine...... sparing effect with at least 80% power in a 24 h trial with RTTE modeling whereas the required sample size was 200 for Mann-Whitney, 180 for t-test and 76 for TTE models. Extending the trial duration from 24 to 96 h reduced the required sample size by 3.1 fold with RTTE modeling. Precise estimate...

  8. Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule Analysis.

    Science.gov (United States)

    Cao, Chan; Long, Yi-Tao

    2018-02-20

    Nanopore sensing is developing into a powerful single-molecule approach to investigate the features of biomolecules that are not accessible by studying ensemble systems. When a target molecule is transported through a nanopore, the ions occupying the pore are excluded, resulting in an electrical signal from the intermittent ionic blockade event. By statistical analysis of the amplitudes, duration, frequencies, and shapes of the blockade events, many properties of the target molecule can be obtained in real time at the single-molecule level, including its size, conformation, structure, charge, geometry, and interactions with other molecules. With the development of the use of α-hemolysin to characterize individual polynucleotides, nanopore technology has attracted a wide range of research interest in the fields of biology, physics, chemistry, and nanoscience. As a powerful single-molecule analytical method, nanopore technology has been applied for the detection of various biomolecules, including oligonucleotides, peptides, oligosaccharides, organic molecules, and disease-related proteins. In this Account, we highlight recent developments of biological nanopores in DNA-based sensing and in studying the conformational structures of DNA and RNA. Furthermore, we introduce the application of biological nanopores to investigate the conformations of peptides affected by charge, length, and dipole moment and to study disease-related proteins' structures and aggregation transitions influenced by an inhibitor, a promoter, or an applied voltage. To improve the sensing ability of biological nanopores and further extend their application to a wider range of molecular sensing, we focus on exploring novel biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits an especially high sensitivity for the detection of single oligonucleotides both in current separation and duration. Finally, to facilitate the use of nanopore measurements and statistical analysis

  9. Single-Trial Classification of Bistable Perception by Integrating Empirical Mode Decomposition, Clustering, and Support Vector Machine

    Directory of Open Access Journals (Sweden)

    Hualou Liang

    2008-04-01

    Full Text Available We propose an empirical mode decomposition (EMD- based method to extract features from the multichannel recordings of local field potential (LFP, collected from the middle temporal (MT visual cortex in a macaque monkey, for decoding its bistable structure-from-motion (SFM perception. The feature extraction approach consists of three stages. First, we employ EMD to decompose nonstationary single-trial time series into narrowband components called intrinsic mode functions (IMFs with time scales dependent on the data. Second, we adopt unsupervised K-means clustering to group the IMFs and residues into several clusters across all trials and channels. Third, we use the supervised common spatial patterns (CSP approach to design spatial filters for the clustered spatiotemporal signals. We exploit the support vector machine (SVM classifier on the extracted features to decode the reported perception on a single-trial basis. We demonstrate that the CSP feature of the cluster in the gamma frequency band outperforms the features in other frequency bands and leads to the best decoding performance. We also show that the EMD-based feature extraction can be useful for evoked potential estimation. Our proposed feature extraction approach may have potential for many applications involving nonstationary multivariable time series such as brain-computer interfaces (BCI.

  10. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  11. Implementation of stimulated Raman scattering microscopy for single cell analysis

    Science.gov (United States)

    D'Arco, Annalisa; Ferrara, Maria Antonietta; Indolfi, Maurizio; Tufano, Vitaliano; Sirleto, Luigi

    2017-05-01

    In this work, we present successfully realization of a nonlinear microscope, not purchasable in commerce, based on stimulated Raman scattering. It is obtained by the integration of a femtosecond SRS spectroscopic setup with an inverted research microscope equipped with a scanning unit. Taking account of strength of vibrational contrast of SRS, it provides label-free imaging of single cell analysis. Validation tests on images of polystyrene beads are reported to demonstrate the feasibility of the approach. In order to test the microscope on biological structures, we report and discuss the label-free images of lipid droplets inside fixed adipocyte cells.

  12. Single base pair mutation analysis by PNA directed PCR clamping

    DEFF Research Database (Denmark)

    Ørum, H.; Nielsen, P.E.; Egholm, M.

    1993-01-01

    A novel method that allows direct analysis of single base mutation by the polymerase chain reaction (PCR) is described. The method utilizes the finding that PNAs (peptide nucleic acids) recognize and bind to their complementary nucleic acid sequences with higher thermal stability and specificity...... allows selective amplification/suppression of target sequences that differ by only one base pair. Finally we show that PNAs can be designed in such a way that blockage can be accomplished when the PNA target sequence is located between the PCR primers....

  13. Replica Analysis for Portfolio Optimization with Single-Factor Model

    Science.gov (United States)

    Shinzato, Takashi

    2017-06-01

    In this paper, we use replica analysis to investigate the influence of correlation among the return rates of assets on the solution of the portfolio optimization problem. We consider the behavior of an optimal solution for the case where the return rate is described with a single-factor model and compare the findings obtained from our proposed methods with correlated return rates with those obtained with independent return rates. We then analytically assess the increase in the investment risk when correlation is included. Furthermore, we also compare our approach with analytical procedures for minimizing the investment risk from operations research.

  14. Optofluidics for handling and analysis of single living cells

    KAUST Repository

    Perozziello, Gerardo

    2017-12-07

    Optofluidics is a field with important applications in areas such as biotechnology, chemical synthesis and analytical chemistry. Optofluidic devices combine optical elements into microfluidic devices in ways that increase portability and sensitivity of analysis for diagnostic or screening purposes .In fact in these devices fluids give fine adaptability, mobility and accessibility to nanoscale photonic devices which otherwise could not be realized using conventional devices. This review describes several cases inwhich optical or microfluidic approaches are used to trap single cells in proximity of integrated optical sensor for being analysed.

  15. Analysis on Single Point Vulnerabilities of Plant Control System

    International Nuclear Information System (INIS)

    Chi, Moon Goo; Lee, Eun Chan; Bae, Yeon Kyoung

    2011-01-01

    The Plant Control System (PCS) is a system that controls pumps, valves, dampers, etc. in nuclear power plants with an OPR-1000 design. When there is a failure or spurious actuation of the critical components in the PCS, it can result in unexpected plant trips or transients. From this viewpoint, single point vulnerabilities are evaluated in detail using failure mode effect analyses (FMEA) and fault tree analyses (FTA). This evaluation demonstrates that the PCS has many vulnerable components and the analysis results are provided for OPR-1000 plants for reliability improvements that can reduce their vulnerabilities

  16. Analysis on Single Point Vulnerabilities of Plant Control System

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Moon Goo; Lee, Eun Chan; Bae, Yeon Kyoung [Korea Hydro and Nuclear Power Co., Daejeon (Korea, Republic of)

    2011-08-15

    The Plant Control System (PCS) is a system that controls pumps, valves, dampers, etc. in nuclear power plants with an OPR-1000 design. When there is a failure or spurious actuation of the critical components in the PCS, it can result in unexpected plant trips or transients. From this viewpoint, single point vulnerabilities are evaluated in detail using failure mode effect analyses (FMEA) and fault tree analyses (FTA). This evaluation demonstrates that the PCS has many vulnerable components and the analysis results are provided for OPR-1000 plants for reliability improvements that can reduce their vulnerabilities.

  17. Optofluidics for handling and analysis of single living cells

    KAUST Repository

    Perozziello, Gerardo; Candeloro, Patrizio; Coluccio, Maria Laura; Di Fabrizio, Enzo M.

    2017-01-01

    Optofluidics is a field with important applications in areas such as biotechnology, chemical synthesis and analytical chemistry. Optofluidic devices combine optical elements into microfluidic devices in ways that increase portability and sensitivity of analysis for diagnostic or screening purposes .In fact in these devices fluids give fine adaptability, mobility and accessibility to nanoscale photonic devices which otherwise could not be realized using conventional devices. This review describes several cases inwhich optical or microfluidic approaches are used to trap single cells in proximity of integrated optical sensor for being analysed.

  18. Cohort analysis of a single nucleotide polymorphism on DNA chips.

    Science.gov (United States)

    Schwonbeck, Susanne; Krause-Griep, Andrea; Gajovic-Eichelmann, Nenad; Ehrentreich-Förster, Eva; Meinl, Walter; Glatt, Hansrüdi; Bier, Frank F

    2004-11-15

    A method has been developed to determine SNPs on DNA chips by applying a flow-through bioscanner. As a practical application we demonstrated the fast and simple SNP analysis of 24 genotypes in an array of 96 spots with a single hybridisation and dissociation experiment. The main advantage of this methodical concept is the parallel and fast analysis without any need of enzymatic digestion. Additionally, the DNA chip format used is appropriate for parallel analysis up to 400 spots. The polymorphism in the gene of the human phenol sulfotransferase SULT1A1 was studied as a model SNP. Biotinylated PCR products containing the SNP (The SNP summary web site: ) (mutant) and those containing no mutation (wild-type) were brought onto the chips coated with NeutrAvidin using non-contact spotting. This was followed by an analysis which was carried out in a flow-through biochip scanner while constantly rinsing with buffer. After removing the non-biotinylated strand a fluorescent probe was hybridised, which is complementary to the wild-type sequence. If this probe binds to a mutant sequence, then one single base is not fully matching. Thereby, the mismatched hybrid (mutant) is less stable than the full-matched hybrid (wild-type). The final step after hybridisation on the chip involves rinsing with a buffer to start dissociation of the fluorescent probe from the immobilised DNA strand. The online measurement of the fluorescence intensity by the biochip scanner provides the possibility to follow the kinetics of the hybridisation and dissociation processes. According to the different stability of the full-match and the mismatch, either visual discrimination or kinetic analysis is possible to distinguish SNP-containing sequence from the wild-type sequence.

  19. Characterizing single-molecule FRET dynamics with probability distribution analysis.

    Science.gov (United States)

    Santoso, Yusdi; Torella, Joseph P; Kapanidis, Achillefs N

    2010-07-12

    Probability distribution analysis (PDA) is a recently developed statistical tool for predicting the shapes of single-molecule fluorescence resonance energy transfer (smFRET) histograms, which allows the identification of single or multiple static molecular species within a single histogram. We used a generalized PDA method to predict the shapes of FRET histograms for molecules interconverting dynamically between multiple states. This method is tested on a series of model systems, including both static DNA fragments and dynamic DNA hairpins. By fitting the shape of this expected distribution to experimental data, the timescale of hairpin conformational fluctuations can be recovered, in good agreement with earlier published results obtained using different techniques. This method is also applied to studying the conformational fluctuations in the unliganded Klenow fragment (KF) of Escherichia coli DNA polymerase I, which allows both confirmation of the consistency of a simple, two-state kinetic model with the observed smFRET distribution of unliganded KF and extraction of a millisecond fluctuation timescale, in good agreement with rates reported elsewhere. We expect this method to be useful in extracting rates from processes exhibiting dynamic FRET, and in hypothesis-testing models of conformational dynamics against experimental data.

  20. Condensing Raman spectrum for single-cell phenotype analysis

    KAUST Repository

    Sun, Shiwei

    2015-12-09

    Background In recent years, high throughput and non-invasive Raman spectrometry technique has matured as an effective approach to identification of individual cells by species, even in complex, mixed populations. Raman profiling is an appealing optical microscopic method to achieve this. To fully utilize Raman proling for single-cell analysis, an extensive understanding of Raman spectra is necessary to answer questions such as which filtering methodologies are effective for pre-processing of Raman spectra, what strains can be distinguished by Raman spectra, and what features serve best as Raman-based biomarkers for single-cells, etc. Results In this work, we have proposed an approach called rDisc to discretize the original Raman spectrum into only a few (usually less than 20) representative peaks (Raman shifts). The approach has advantages in removing noises, and condensing the original spectrum. In particular, effective signal processing procedures were designed to eliminate noise, utilising wavelet transform denoising, baseline correction, and signal normalization. In the discretizing process, representative peaks were selected to signicantly decrease the Raman data size. More importantly, the selected peaks are chosen as suitable to serve as key biological markers to differentiate species and other cellular features. Additionally, the classication performance of discretized spectra was found to be comparable to full spectrum having more than 1000 Raman shifts. Overall, the discretized spectrum needs about 5storage space of a full spectrum and the processing speed is considerably faster. This makes rDisc clearly superior to other methods for single-cell classication.

  1. Use of a single implant to retain mandibular overdenture: A preliminary clinical trial of 13 cases

    Directory of Open Access Journals (Sweden)

    Tao Cheng

    2012-09-01

    Conclusion: Within the limitations of this preliminary prospective clinical study, single-implant-supported mandibular overdentures were a successful alternative treatment option for elderly edentulous patients.

  2. A randomized controlled trial of single point acupuncture in primary dysmenorrhea.

    Science.gov (United States)

    Liu, Cun-Zhi; Xie, Jie-Ping; Wang, Lin-Peng; Liu, Yu-Qi; Song, Jia-Shan; Chen, Yin-Ying; Shi, Guang-Xia; Zhou, Wei; Gao, Shu-Zhong; Li, Shi-Liang; Xing, Jian-Min; Ma, Liang-Xiao; Wang, Yan-Xia; Zhu, Jiang; Liu, Jian-Ping

    2014-06-01

    Acupuncture is often used for primary dysmenorrhea. But there is no convincing evidence due to low methodological quality. We aim to assess immediate effect of acupuncture at specific acupoint compared with unrelated acupoint and nonacupoint on primary dysmenorrhea. The Acupuncture Analgesia Effect in Primary Dysmenorrhoea-II is a multicenter controlled trial conducted in six large hospitals of China. Patients who met inclusion criteria were randomly assigned to classic acupoint (N = 167), unrelated acupoint (N = 167), or non-acupoint (N = 167) group on a 1:1:1 basis. They received three sessions with electro-acupuncture at a classic acupoint (Sanyinjiao, SP6), or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location, respectively. The primary outcome was subjective pain as measured by a 100-mm visual analog scale (VAS). Measurements were obtained at 0, 5, 10, 30, and 60 minutes following the first intervention. In addition, patients scored changes of general complaints using Cox retrospective symptom scales (RSS-Cox) and 7-point verbal rating scale (VRS) during three menstrual cycles. Secondary outcomes included VAS score for average pain, pain total time, additional in-bed time, and proportion of participants using analgesics during three menstrual cycles. Five hundred and one people underwent random assignment. The primary comparison of VAS scores following the first intervention demonstrated that classic acupoint group was more effective both than unrelated acupoint (-4.0 mm, 95% CI -7.1 to -0.9, P = 0.010) and nonacupoint (-4.0 mm, 95% CI -7.0 to -0.9, P = 0.012) groups. However, no significant differences were detected among the three acupuncture groups for RSS-Cox or VRS outcomes. The per-protocol analysis showed similar pattern. No serious adverse events were noted. Specific acupoint acupuncture produced a statistically, but not clinically, significant effect compared with unrelated acupoint and nonacupoint acupuncture in

  3. The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

    Science.gov (United States)

    Matusz, Pawel J; Thelen, Antonia; Amrein, Sarah; Geiser, Eveline; Anken, Jacques; Murray, Micah M

    2015-03-01

    Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d') were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single-trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long-term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Pressure relieving support surfaces (PRESSURE) trial: cost effectiveness analysis.

    Science.gov (United States)

    Iglesias, Cynthia; Nixon, Jane; Cranny, Gillian; Nelson, E Andrea; Hawkins, Kim; Phillips, Angela; Torgerson, David; Mason, Su; Cullum, Nicky

    2006-06-17

    To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital. Cost effectiveness analysis carried out alongside the pressure relieving support surfaces (PRESSURE) trial; a multicentre UK based pragmatic randomised controlled trial. 11 hospitals in six UK NHS trusts. Intention to treat population comprising 1971 participants. Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital. Alternating pressure mattresses were associated with lower overall costs (283.6 pounds sterling per patient on average, 95% confidence interval--377.59 pounds sterling to 976.79 pounds sterling) mainly due to reduced length of stay in hospital, and greater benefits (a delay in time to ulceration of 10.64 days on average,--24.40 to 3.09). The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant; however, a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80% probability of being cost saving. Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays.

  5. A new analysis of the Vixen A Trials

    International Nuclear Information System (INIS)

    Luna, R.E.

    1994-02-01

    The source term for assessing events that involve the combustion of metallic plutonium (Pu) presents a continuing need in carrying out safety evaluations in support of DOE programs involving nuclear weapons. For production, storage, transport and decommissioning operations, an accident sequence that frequently must be evaluated involves metallic Pu being exposed in a fire environment. There are significant data on which to base an estimate for the source term which has been surveyed recently by Mishima et al (Mishima, 1993), but much of the surveyed work relates to well controlled laboratory experiments with relatively small amounts of Pu. One of the most relevant sources of information was the work by Stewart (Stewart, 1959) of the UK Atomic Weapon Research Establishment at Aldermaston. That work, referred to as the Vixen A Trials provides direct experimental data on the aerosolization and environmental releases from relatively large metallic Pu shapes immersed in a ''petrol'' fire. A new analysis of the air sampler data from the two Vixen A Trials experiments involving chunks of plutonium exposed to hydrocarbon fuel fires indicated a respirable release fraction (referenced to total plutonium involved) of 0.0001 to 0.0003 (1 E-4 to 3 E-4) depending on the parameters used in the atmospheric transport and dispersion model used. A value of 3 E-4 is recommended as an upper limit for use in safety assessment studies involving similar accident scenarios

  6. Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

    DEFF Research Database (Denmark)

    Dunning, Jake; Sahr, Foday; Rojek, Amanda

    2016-01-01

    BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD...... of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma...

  7. Treating Acute Insomnia: A Randomized Controlled Trial of a “Single-Shot” of Cognitive Behavioral Therapy for Insomnia

    Science.gov (United States)

    Ellis, Jason G.; Cushing, Toby; Germain, Anne

    2015-01-01

    Study Objectives: Despite considerable evidence supporting cognitive behavioral therapy for insomnia (CBT-I) for chronic insomnia, it remains untested within the context of acute insomnia. This study examined the efficacy of a single session of CBT-I, with an accompanying self-help pamphlet, for individuals with acute insomnia. Design: A pragmatic parallel group randomized controlled trial. Setting: Community. Participants: Forty adults (mean age 32.9 ± 13.72 y) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defined insomnia disorder, except a self-reported duration of less than 3 mo (i.e., acute insomnia), who reported no previous exposure to CBT-I and were not currently taking medication for sleep. Interventions: A single 60- to 70-min session of CBT-I (n = 20), with an accompanying self-help pamphlet, or wait list control group (n = 20). All subjects were offered a full individual course of CBT-I on completion of the study, regardless of group allocation. Measurements and Results: Subjects completed sleep diaries and the Insomnia Severity Index (ISI) pretreatment and 1 mo following treatment. There were no between-group differences on baseline ISI scores or subjective sleep continuity. The intervention group reported significantly lower ISI scores than controls (t(38) 2.24, P insomnia caseness (i.e., ≥ 10), 60% of those in the CBT-I group had remitted by 1 mo compared to 15% of those in the control group. Conclusions: This single session of cognitive behavioral therapy for insomnia (CBT-I) is sufficiently efficacious for a significant proportion of those with acute insomnia. The results are discussed in terms of integrating this brief form of CBT-I into the “stepped care” model of insomnia. Trial Registration: Testing the efficacy of an early intervention for acute insomnia (SRCTN05891695) http://www.controlled-trials.com/ISRCTN05891695. Citation: Ellis JG, Cushing T, Germain A. Treating acute insomnia: a randomized

  8. Evaluation of the Utility of a Discrete-Trial Functional Analysis in Early Intervention Classrooms

    Science.gov (United States)

    Kodak, Tiffany; Fisher, Wayne W.; Paden, Amber; Dickes, Nitasha

    2013-01-01

    We evaluated a discrete-trial functional analysis implemented by regular classroom staff in a classroom setting. The results suggest that the discrete-trial functional analysis identified a social function for each participant and may require fewer staff than standard functional analysis procedures.

  9. Classroom Application of a Trial-Based Functional Analysis

    Science.gov (United States)

    Bloom, Sarah E.; Iwata, Brian A.; Fritz, Jennifer N.; Roscoe, Eileen M.; Carreau, Abbey B.

    2011-01-01

    We evaluated a trial-based approach to conducting functional analyses in classroom settings. Ten students referred for problem behavior were exposed to a series of assessment trials, which were interspersed among classroom activities throughout the day. Results of these trial-based functional analyses were compared to those of more traditional…

  10. An interim analysis of recruitment to the COLOFOL trial

    DEFF Research Database (Denmark)

    Wille-Jørgensen, Peer; Laurberg, S.; Pahlman, L.

    2009-01-01

    Objective To analyse the ongoing process of recruiting patients into a multicenter randomized trial on follow-up after curative surgery for colorectal cancer. The trial is registered in Clinical Trials Registration. Method Prospective registration of all operated patients as well as inclusions...

  11. Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

    Science.gov (United States)

    Kaneko, Reina; Sano, Kota; Ono, Shunsuke

    2018-07-01

    The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

  12. Impact of adding a second-layer to a single unlocked closure of Cesarean uterine incision: a randomized controlled trial

    DEFF Research Database (Denmark)

    Rudnicki, Martin; Bennich, G; Wilken-Jensen, C

    2016-01-01

    the criteria and accepted participation. Thirty-eight women were assigned to single-layer and 38 to double-layer unlocked closure technique. Groups were comparable regarding gestational age at delivery, duration of surgery and peroperative blood loss. RMT was without difference between the two groups, both......The purpose of the present study was to investigate short- and long term effects on residual myometrial thickness (RMT) by adding a second-layer to a single unlocked closure of caesarean uterine incision. METHOD: he study was a randomized double-blind controlled trial. Healthy nulliparous scheduled...... for first-time elective Caesarean delivery were operated using a modified version of the Misgav-Ladach surgical technique. The women were examined by abdominal ultrasound before discharge from the maternity ward and by hysterosonography five months post partum. RESULTS: Seventy-six nulliparous met...

  13. A pharmacoeconomic analysis of the use of single MMC instillation in low risk NMIBC in Italy

    Directory of Open Access Journals (Sweden)

    Renzo Colombo

    2013-03-01

    Full Text Available BACKGROUND: Bladder cancer accounts for 5-10% of all cancers in Europe and up to 85% patients presents a noninvasive tumor, whose treatment of choice is the transurethral bladder resection (TURB paired with adjuvant intravesical chemotherapy or immunotherapy. Despite several clinical trials showed that this treatment is safe and decreases recurrences by 17% to 44% this practice is limited for many reasons. The study objective is to analyze the economical advantages of the single immediate post operative Mitomycin C instillation in Non Muscle-invasive Bladder Cancer (NMIBC low-risk patients.METHODS: A cost-benefit analysis was performed evaluating the economical gain that would raised from a scenario with a single immediate post operative mitomycin C instillation in each low-risk NMIBC patient who underwent to TURB. Net present value and cost-benefit ratio were calculated and sensitivity analyses were performed. Base case analysis was performed considering tumor recurrence rate reduction of 11.7% and a TURB costs of 2,167.0 €, while sensitivity analyses were performed using a recurrence rate reduction of 19.2% and 15.0% and a TURB cost of 2,472.93 €. The discount rate was 2%.RESULTS: The single immediate post operative instillation of mitomycin C resulted to be cost-beneficial with a cost-benefit ratio that goes from 0.48 to 0.79 when compared to TURB alone raising a Net Present Value that goes from 660,284.39 € to 2,650,530.79 €.CONCLUSION: This study demonstrates that even assuming conservative parameters for recurrence rates reduction, a single immediate post operative mitomycin C instillation in low risk NMIBC patients would lower not only the recurrence rate but also the caring cost for bladder cancer.

  14. Single particle analysis with a 3600 light scattering photometer

    International Nuclear Information System (INIS)

    Bartholdi, M.F.

    1979-06-01

    Light scattering by single spherical homogeneous particles in the diameter range 1 to 20 μm and relative refractive index 1.20 is measured. Particle size of narrowly dispersed populations is determined and a multi-modal dispersion of five components is completely analyzed. A 360 0 light scattering photometer for analysis of single particles has been designed and developed. A fluid stream containing single particles intersects a focused laser beam at the primary focal point of an ellipsoidal reflector ring. The light scattered at angles theta = 2.5 0 to 177.5 0 at phi = 0 0 and 180 0 is reflected onto a circular array of photodiodes. The ellipsoidal reflector is situated in a chamber filled with fluid matching that of the stream to minimize refracting and reflecting interfaces. The detector array consists of 60 photodiodes each subtending 3 0 in scattering angle on 6 0 centers around 360 0 . 32 measurements on individual particles can be acquired at rates of 500 particles per second. The intensity and angular distribution of light scattered by spherical particles are indicative of size and relative refractive index. Calculations, using Lorenz--Mie theory, of differential scattering patterns integrated over angle corresponding to the detector geometry determined the instrument response to particle size. From this the expected resolution and experimental procedures are determined.Ultimately, the photometer will be utilized for identification and discrimination of biological cells based on the sensitivity of light scattering to size, shape, refractive index differences, internal granularity, and other internal morphology. This study has demonstrated the utility of the photometer and indicates potential for application to light scattering studies of biological cells

  15. Single and combined effects of beetroot juice and caffeine supplementation on cycling time trial performance.

    Science.gov (United States)

    Lane, Stephen C; Hawley, John A; Desbrow, Ben; Jones, Andrew M; Blackwell, James R; Ross, Megan L; Zemski, Adam J; Burke, Louise M

    2014-09-01

    Both caffeine and beetroot juice have ergogenic effects on endurance cycling performance. We investigated whether there is an additive effect of these supplements on the performance of a cycling time trial (TT) simulating the 2012 London Olympic Games course. Twelve male and 12 female competitive cyclists each completed 4 experimental trials in a double-blind Latin square design. Trials were undertaken with a caffeinated gum (CAFF) (3 mg·kg(-1) body mass (BM), 40 min prior to the TT), concentrated beetroot juice supplementation (BJ) (8.4 mmol of nitrate (NO3(-)), 2 h prior to the TT), caffeine plus beetroot juice (CAFF+BJ), or a control (CONT). Subjects completed the TT (females: 29.35 km; males: 43.83 km) on a laboratory cycle ergometer under conditions of best practice nutrition: following a carbohydrate-rich pre-event meal, with the ingestion of a carbohydrate-electrolyte drink and regular oral carbohydrate contact during the TT. Compared with CONT, power output was significantly enhanced after CAFF+BJ and CAFF (3.0% and 3.9%, respectively, p caffeine (-0.9%, p = 0.4 compared with CAFF). We conclude that caffeine (3 mg·kg(-1) BM) administered in the form of a caffeinated gum increased cycling TT performance lasting ∼50-60 min by ∼3%-4% in both males and females. Beetroot juice supplementation was not ergogenic under the conditions of this study.

  16. Efficacy and safety of cross-cylinder photorefractive keratectomy versus single method in medium-high astigmatism: a randomized clinical trial.

    Science.gov (United States)

    Sedghipour, Mohammad R; Lotfi, Afshin; Sadeghilar, Ayaz; Banan, Saeeid

    2012-09-07

    BACKGROUND: To compare efficacy and safety of photorefractive keratectomy (PRK) by cross-cylinder with single methods in medium-high astigmatism. DESIGN: Randomized clinical trial study PARTICIPANTS: Fifty patients with medium-high compound myopic astigmatism were enrolled between September 2007 and September 2008. METHODS: PRK was performed on 100 eyes of 50 patients with compound myopic astigmatism. Each patient underwent PRK by cross-cylinder approach in one eye and single method on the contralateral eye. Vector analysis was used to assess astigmatic results. MAIN OUTCOME MEASURES: Improvement of visual acuity (snelen chart), refraction, aberrometry. RESULTS: Uncorrected visual acuity (UCCA) equal to 20/40 or better after six months, was achieved in 98% of eyes in the cross-cylinder method versus 96% in single method.. Mean preoperative spherical equivalent(SE) was -5.2 ±2.1 D in the cross-cylinder method versus -5.1 ±0.5 D in the single method. At six months, the mean SE was - 0.5±0.4 D and -0.6±0.3 D, respectively. Mean IOS was 0.4±0.3 in the cross-cylinder group and 0.4±0.4 in the single group. Mean postoperative absolute change in total root-mean-square higher order aberrations in the cross-cylinder group and single group were 0.16 pm and 0.17 pm, respectively. Any of the mentioned differences didn't appear to be statistically significant. CONCLUSIONS: Both PRK methods appeared to be safe and effective in correcting medium-high astigmatism. © 2012 The Author. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  17. Size analysis of single-core magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Ludwig, Frank, E-mail: f.ludwig@tu-bs.de [Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig (Germany); Balceris, Christoph; Viereck, Thilo [Institut für Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig (Germany); Posth, Oliver; Steinhoff, Uwe [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Gavilan, Helena; Costo, Rocio [Instituto de Ciencia de Materiales de Madrid, ICMM/CSIC, Madrid (Spain); Zeng, Lunjie; Olsson, Eva [Department of Applied Physics, Chalmers University of Technology, Göteborg (Sweden); Jonasson, Christian; Johansson, Christer [ACREO Swedish ICT AB, Göteborg (Sweden)

    2017-04-01

    Single-core iron-oxide nanoparticles with nominal core diameters of 14 nm and 19 nm were analyzed with a variety of non-magnetic and magnetic analysis techniques, including transmission electron microscopy (TEM), dynamic light scattering (DLS), static magnetization vs. magnetic field (M-H) measurements, ac susceptibility (ACS) and magnetorelaxometry (MRX). From the experimental data, distributions of core and hydrodynamic sizes are derived. Except for TEM where a number-weighted distribution is directly obtained, models have to be applied in order to determine size distributions from the measurand. It was found that the mean core diameters determined from TEM, M-H, ACS and MRX measurements agree well although they are based on different models (Langevin function, Brownian and Néel relaxation times). Especially for the sample with large cores, particle interaction effects come into play, causing agglomerates which were detected in DLS, ACS and MRX measurements. We observed that the number and size of agglomerates can be minimized by sufficiently strong diluting the suspension. - Highlights: • Investigation of size parameters of single-core magnetic nanoparticles with nominal core diameters of 14 nm and 19 nm utilizing different magnetic and non-magnetic methods • Hydrodynamic size determined from ac susceptibility measurements is consistent with the DLS findings • Core size agrees determined from static magnetization curves, MRX and ACS data agrees with results from TEM although the estimation is based on different models (Langevin function, Brownian and Néel relaxation times).

  18. The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only.

    Science.gov (United States)

    Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

    2015-11-01

    Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score definition), or GCSdefinition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), pdefinition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. This trial suggests a potential mortality reduction in patients with blunt trauma with GCSdefinition only). Confirmatory studies which also address non-compliance issues are needed. NCT00112398. 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.

  19. Adolescent survivors: a secondary analysis of a clinical trial targeting behavior change.

    Science.gov (United States)

    Cox, Cheryl L; McLaughlin, Rosemary A; Rai, Shesh N; Steen, Brenda D; Hudson, Melissa M

    2005-08-01

    The late effects of radiation and chemotherapy increase childhood cancer survivors' risk of chronic health problems. Survivors' behavior is important in modifying this risk, yet adolescent and young adult survivors fail to engage in important health-promoting behaviors and frequently practice high-risk behaviors. This secondary analysis re-evaluated a multi-component behavior-change intervention that had previously demonstrated no impact in adolescent survivors of childhood cancer. The parent trial compared 132 adolescent survivors in the intervention arm with 135 in the standard-care arm at baseline and at 1 year for disease and treatment knowledge, perception of late effects risk, and the frequency of health-risk and health-protective behaviors (combined as a single summative measure). In contrast, the secondary analysis examined each of the 14 behaviors separately. Additionally, an analysis of covariance (ANCOVA) was conducted to examine the change in health behaviors while statistically controlling for age, gender, and the wide variation in baseline behaviors. Knowledge (P = 0.038), breast self-examination (BSE) (P junk food consumption decreased (P = 0.052) and smoking abstinence was maintained (P = 0.088). Significant interactions between gender and treatment group were demonstrated. Health-risk and health-protective behaviors cannot be effectively combined in a one-dimensional measure. Gender and age influence the impact of interventions targeting health behavior in survivors. Future trials should include observation of the patient-clinician encounter, more complex sampling methods, and pre-trial knowledge of the distribution of the study behaviors.

  20. Precision of Carbon-14 analysis in a single laboratory

    International Nuclear Information System (INIS)

    Nashriyah Mat; Misman Sumin; Holland, P.T.

    2009-01-01

    In a single laboratory, one operator has used a Biological Material Oxidizer (BMO) unit to prepare (combust) solid samples before analyzing (counting) the radioactivity by using various Liquid Scintillation Counters (LSCs). The different batches of commercially available solid Certified Reference Material (CRM, Amersham, UK) standards were analyzed depending on the time of analysis over a period of seven years. The certified radioactivity and accuracy of the C-14 standards as cellulose tabs, designated as the Certified Reference Material (CRM), was 5000 + 3% DPM. Each analysis was carried out using triplicate tabs. The medium of counting was commercially available cocktail containing the sorbent solution for the oxidizer gases, although of different batches were used depending on the date of analysis. The mean DPM of the solutions was measured after correction for quenching by the LSC internal standard procedure and subtracting the mean DPM of control. The precisions of the standard and control counts and of the recovery percentage for the CRM were measured as the coefficients of variation (CV), for the C-14 determination over the seven year period. The results from a recently acquired Sample Oxidizer unit were also included for comparison. (Author)

  1. Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

    Science.gov (United States)

    Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

    2016-03-22

    To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

  2. Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database

    International Nuclear Information System (INIS)

    Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M.; Lössl, Kristina

    2016-01-01

    To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future. The online version of this article (doi:10.1186/s13014-016-0624-8) contains supplementary material, which is available to authorized users

  3. Analysis of time to event outcomes in randomized controlled trials by generalized additive models.

    Directory of Open Access Journals (Sweden)

    Christos Argyropoulos

    Full Text Available Randomized Controlled Trials almost invariably utilize the hazard ratio calculated with a Cox proportional hazard model as a treatment efficacy measure. Despite the widespread adoption of HRs, these provide a limited understanding of the treatment effect and may even provide a biased estimate when the assumption of proportional hazards in the Cox model is not verified by the trial data. Additional treatment effect measures on the survival probability or the time scale may be used to supplement HRs but a framework for the simultaneous generation of these measures is lacking.By splitting follow-up time at the nodes of a Gauss Lobatto numerical quadrature rule, techniques for Poisson Generalized Additive Models (PGAM can be adopted for flexible hazard modeling. Straightforward simulation post-estimation transforms PGAM estimates for the log hazard into estimates of the survival function. These in turn were used to calculate relative and absolute risks or even differences in restricted mean survival time between treatment arms. We illustrate our approach with extensive simulations and in two trials: IPASS (in which the proportionality of hazards was violated and HEMO a long duration study conducted under evolving standards of care on a heterogeneous patient population.PGAM can generate estimates of the survival function and the hazard ratio that are essentially identical to those obtained by Kaplan Meier curve analysis and the Cox model. PGAMs can simultaneously provide multiple measures of treatment efficacy after a single data pass. Furthermore, supported unadjusted (overall treatment effect but also subgroup and adjusted analyses, while incorporating multiple time scales and accounting for non-proportional hazards in survival data.By augmenting the HR conventionally reported, PGAMs have the potential to support the inferential goals of multiple stakeholders involved in the evaluation and appraisal of clinical trial results under proportional and

  4. Renormalisation group analysis of single right-handed neutrino dominance

    International Nuclear Information System (INIS)

    King, S.F.; Nimai Singh, N.

    2000-01-01

    We perform a renormalisation group (RG) analysis of neutrino masses and mixing angles in the see-saw mechanism in the minimal supersymmetric standard model with three right-handed neutrinos, including the effects of the heavy neutrino thresholds. We focus on the case that one of the right-handed neutrinos provides the dominant contribution to the 23 block of the light Majorana matrix, causing its determinant to approximately vanish and giving an automatic neutrino mass hierarchy, so-called single right-handed neutrino dominance which may arise from a U(1) family symmetry. In these models radiative corrections can increase atmospheric and solar neutrino mixing by up to about 10% and 5%, respectively, and may help to achieve bi-maximal mixing. Significantly we find that the radiative corrections over the heavy neutrino threshold region are at least as important as those usually considered from the lightest right-handed neutrino down to low energies

  5. The Weibull probabilities analysis on the single kenaf fiber

    Science.gov (United States)

    Ibrahim, I.; Sarip, S.; Bani, N. A.; Ibrahim, M. H.; Hassan, M. Z.

    2018-05-01

    Kenaf fiber has a great potential to be replaced with the synthetic composite due to their advantages such as environmentally friendly and outstanding performance. However, the main issue of this natural fiber that to be used in structural composite is inconsistency of their mechanical properties. Here, the influence of the gage length on the mechanical properties of single kenaf fiber was evaluated. This fiber was tested using the Universal testing machine at a loading rate of 1mm per min following ASTM D3822 standard. In this study, the different length of treated fiber including 20, 30 and 40mm were being tested. Following, Weibull probabilities analysis was used to characterize the tensile strength and Young modulus of kenaf fiber. The predicted average tensile strength from this approach is in good agreement with experimental results for the obtained parameter.

  6. Robust stability analysis of adaptation algorithms for single perceptron.

    Science.gov (United States)

    Hui, S; Zak, S H

    1991-01-01

    The problem of robust stability and convergence of learning parameters of adaptation algorithms in a noisy environment for the single preceptron is addressed. The case in which the same input pattern is presented in the adaptation cycle is analyzed. The algorithm proposed is of the Widrow-Hoff type. It is concluded that this algorithm is robust. However, the weight vectors do not necessarily converge in the presence of measurement noise. A modified version of this algorithm in which the reduction factors are allowed to vary with time is proposed, and it is shown that this algorithm is robust and that the weight vectors converge in the presence of bounded noise. Only deterministic-type arguments are used in the analysis. An ultimate bound on the error in terms of a convex combination of the initial error and the bound on the noise is obtained.

  7. Analysis of DNA interactions using single-molecule force spectroscopy.

    Science.gov (United States)

    Ritzefeld, Markus; Walhorn, Volker; Anselmetti, Dario; Sewald, Norbert

    2013-06-01

    Protein-DNA interactions are involved in many biochemical pathways and determine the fate of the corresponding cell. Qualitative and quantitative investigations on these recognition and binding processes are of key importance for an improved understanding of biochemical processes and also for systems biology. This review article focusses on atomic force microscopy (AFM)-based single-molecule force spectroscopy and its application to the quantification of forces and binding mechanisms that lead to the formation of protein-DNA complexes. AFM and dynamic force spectroscopy are exciting tools that allow for quantitative analysis of biomolecular interactions. Besides an overview on the method and the most important immobilization approaches, the physical basics of the data evaluation is described. Recent applications of AFM-based force spectroscopy to investigate DNA intercalation, complexes involving DNA aptamers and peptide- and protein-DNA interactions are given.

  8. Effect of Auricular Acupress Therapy on Insomnia of Cancer Patients : Randomized, Single Blinded, Placebo Controlled Trial

    Directory of Open Access Journals (Sweden)

    In-Sook Jung

    2010-06-01

    Full Text Available Background: Auricular acupressure is one of the traditional health care treatments in oriental medicine. Approximately, 30~40% of the cancer patients have said to be suffering from insomnia and half of them having chronic and severe insomnia at the same time. Insomnia caused cancer patients feel more pain, fatigue, depression and anxiety and it sometimes let the power to have the best of cancer pull down. Objective: To investigate how effective the auricular acupressure treatment to cancer patients suffering from insomnia. Methods: We recruited participants from East-West Cancer Center of Daejeon University. Finally, of the people whose age range from 20 to 75, 12 patients who got less than 40 points from the score of Oh's sleeping score (OSS were recruited. Single-blind, randomized pilot study was performed. The treatment group received auricular acupressure treatment (AAT on active points and the control group had received sham acupressure treatment (SAT for five times. Sleep parameters were checked by using OSS and numeric rating scale (NRS. We checked the scale everytime, both before and after treatment. We analyzed the data statistically by using independent T-test, paired T-test and analysis of variance (ANOVA test. (p<0.05 Results: Twelve cancer patients participated in this pilot study and there was no significant difference between control and treatment group. Only 7 of them had completed the whole treatment process, 4 patients of AAT group and 3 participants of SAT. The OSS of AAT group had increased from 34.0± 4.3 to 39.5±3.1 and that of SAT group had increased from 38.3±3.5 to 40.0±0.0. There was no significant difference between them. The NRS of AAT group had increased from 6.3±2.9 to 4.8±2.1 and that of SAT group had increased from 7.0±1.0 to 5.0±2.6. No significant difference was observed between them. Conclusion: Although both groups did not show significant differences, most of the experimental participants showed

  9. Offline identification of imagined speed of wrist movements in paralyzed ALS patients from single-trial EEG

    Directory of Open Access Journals (Sweden)

    Ying Gu

    2009-08-01

    Full Text Available The study investigated the possibility of identifying the speed of an imagined movement from EEG recordings in amyotrophic lateral sclerosis (ALS patients. EEG signals were acquired from four ALS patients during imagination of wrist extensions at two speeds (fast and slow, each repeated up to 100 times in random order. The movement-related cortical potentials (MRCPs and averaged sensorimotor rhythm associated with the two tasks were obtained from the EEG recordings. Moreover, offline single-trial EEG classification was performed with discrete wavelet transform for feature extraction and support vector machine for classification. The speed of the task was encoded in the time delay of peak negativity in the MRCPs, which was shorter for faster than for slower movements. The average single-trial misclassification rate between speeds was 30.4 ± 3.5 % when the best scalp location and time interval were selected for each individual. The scalp location and time interval leading to the lowest misclassification rate varied among patients. The results indicate that the imagination of movements at different speeds is a viable strategy for controlling a brain-computer interface system by ALS patients.

  10. A fast and reliable method for simultaneous waveform, amplitude and latency estimation of single-trial EEG/MEG data.

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    Wouter D Weeda

    Full Text Available The amplitude and latency of single-trial EEG/MEG signals may provide valuable information concerning human brain functioning. In this article we propose a new method to reliably estimate single-trial amplitude and latency of EEG/MEG signals. The advantages of the method are fourfold. First, no a-priori specified template function is required. Second, the method allows for multiple signals that may vary independently in amplitude and/or latency. Third, the method is less sensitive to noise as it models data with a parsimonious set of basis functions. Finally, the method is very fast since it is based on an iterative linear least squares algorithm. A simulation study shows that the method yields reliable estimates under different levels of latency variation and signal-to-noise ratioÕs. Furthermore, it shows that the existence of multiple signals can be correctly determined. An application to empirical data from a choice reaction time study indicates that the method describes these data accurately.

  11. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  12. A Validated Task Analysis of the Single Pilot Operations Concept

    Science.gov (United States)

    Wolter, Cynthia A.; Gore, Brian F.

    2015-01-01

    The current day flight deck operational environment consists of a two-person Captain/First Officer crew. A concept of operations (ConOps) to reduce the commercial cockpit to a single pilot from the current two pilot crew is termed Single Pilot Operations (SPO). This concept has been under study by researchers in the Flight Deck Display Research Laboratory (FDDRL) at the National Aeronautics and Space Administration's (NASA) Ames (Johnson, Comerford, Lachter, Battiste, Feary, and Mogford, 2012) and researchers from Langley Research Centers (Schutte et al., 2007). Transitioning from a two pilot crew to a single pilot crew will undoubtedly require changes in operational procedures, crew coordination, use of automation, and in how the roles and responsibilities of the flight deck and ATC are conceptualized in order to maintain the high levels of safety expected of the US National Airspace System. These modifications will affect the roles and the subsequent tasks that are required of the various operators in the NextGen environment. The current report outlines the process taken to identify and document the tasks required by the crew according to a number of operational scenarios studied by the FDDRL between the years 2012-2014. A baseline task decomposition has been refined to represent the tasks consistent with a new set of entities, tasks, roles, and responsibilities being explored by the FDDRL as the move is made towards SPO. Information from Subject Matter Expert interviews, participation in FDDRL experimental design meetings, and study observation was used to populate and refine task sets that were developed as part of the SPO task analyses. The task analysis is based upon the proposed ConOps for the third FDDRL SPO study. This experiment possessed nine different entities operating in six scenarios using a variety of SPO-related automation and procedural activities required to guide safe and efficient aircraft operations. The task analysis presents the roles and

  13. Effectiveness of a single-session early psychological intervention for children after road traffic accidents: a randomised controlled trial

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    Meuli Martin

    2010-02-01

    Full Text Available Abstract Background Road traffic accidents (RTAs are the leading health threat to children in Europe, resulting in 355 000 injuries annually. Because children can suffer significant and long-term mental health problems following RTAs, there is considerable interest in the development of early psychological interventions. To date, the research in this field is scarce, and currently no evidence-based recommendations can be made. Methods To evaluate the effectiveness of a single-session early psychological intervention, 99 children age 7-16 were randomly assigned to an intervention or control group. The manualised intervention was provided to the child and at least one parent around 10 days after the child's involvement in an RTA. It included reconstruction of the accident using drawings and accident-related toys, and psychoeducation. All of the children were interviewed at 10 days, 2 months and 6 months after the accident. Parents filled in questionnaires. Standardised instruments were used to assess acute stress disorder (ASD, posttraumatic stress disorder (PTSD, depressive symptoms and behavioural problems. Results The children of the two study groups showed no significant differences concerning posttraumatic symptoms and other outcome variables at 2 or at 6 months. Interestingly, analyses showed a significant intervention × age-group effect, indicating that for preadolescent children the intervention was effective in decreasing depressive symptoms and behavioural problems. Conclusions This study is the first to show a beneficial effect of a single-session early psychological intervention after RTA in preadolescent children. Therefore, an age-specific approach in an early stage after RTAs may be a promising way for further research. Younger children can benefit from the intervention evaluated here. However, these results have to be interpreted with caution, because of small subgroup sizes. Future studies are needed to examine specific

  14. Group-Level EEG-Processing Pipeline for Flexible Single Trial-Based Analyses Including Linear Mixed Models.

    Science.gov (United States)

    Frömer, Romy; Maier, Martin; Abdel Rahman, Rasha

    2018-01-01

    Here we present an application of an EEG processing pipeline customizing EEGLAB and FieldTrip functions, specifically optimized to flexibly analyze EEG data based on single trial information. The key component of our approach is to create a comprehensive 3-D EEG data structure including all trials and all participants maintaining the original order of recording. This allows straightforward access to subsets of the data based on any information available in a behavioral data structure matched with the EEG data (experimental conditions, but also performance indicators, such accuracy or RTs of single trials). In the present study we exploit this structure to compute linear mixed models (LMMs, using lmer in R) including random intercepts and slopes for items. This information can easily be read out from the matched behavioral data, whereas it might not be accessible in traditional ERP approaches without substantial effort. We further provide easily adaptable scripts for performing cluster-based permutation tests (as implemented in FieldTrip), as a more robust alternative to traditional omnibus ANOVAs. Our approach is particularly advantageous for data with parametric within-subject covariates (e.g., performance) and/or multiple complex stimuli (such as words, faces or objects) that vary in features affecting cognitive processes and ERPs (such as word frequency, salience or familiarity), which are sometimes hard to control experimentally or might themselves constitute variables of interest. The present dataset was recorded from 40 participants who performed a visual search task on previously unfamiliar objects, presented either visually intact or blurred. MATLAB as well as R scripts are provided that can be adapted to different datasets.

  15. Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

    NARCIS (Netherlands)

    Moet, F. Johannes; Pahan, David; Oskam, Linda; Richardus, Jan H.; van Brakel, Wim H.; Klatser, Paul R.; Saunderson, Paul R.; Smith, W. Cairns S.; Withington, Steve G.; Richardus, Jan Hendrik; Schuring, Ron P.; Faber, Roel; Borsboom, Gerard J. J. M.

    2008-01-01

    OBJECTIVE: To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. DESIGN: Single centre, double blind, cluster randomised, placebo controlled trial. SETTING: Leprosy control programme in two districts of northwest Bangladesh with a

  16. COLLABORATIVE TRIAL AND QUALITY CONTROL IN CHEMICAL ANALYSIS

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    Narsito Narsito

    2010-06-01

    Full Text Available Abstract                                                             This paper deals with some practical problems related to the quality of analytical chemical data usually met in practice. Special attention is given to the topic of quality control in analytical chemistry, since analytical data is one of the primary information from which some important scientifically based decision are to be made. The present paper starts with brief description on some fundamental aspects associated with quality of analytical data, such as sources of variation of analytical data, criteria for quality of analytical method, quality assurance in chemical analysis. The assessment of quality parameter for analytical method like the use of standard materials as well as standard methods is given. Concerning with the quality control of analytical data, the use of several techniques, such as control samples and control charts, in monitoring analytical data in quality control program are described qualitatively.  In the final part of this paper, some important remarks for the preparation of collaborative trials, including the evaluation of accuracy and reproducibility of analytical method are also given Keywords: collaborative trials, quality control, analytical data Abstract                                                             This paper deals with some practical problems related to the quality of analytical chemical data usually met in practice. Special attention is given to the topic of quality control in analytical chemistry, since analytical data is one of the primary information from which some important scientifically based decision are to be made. The present paper starts with brief description on some fundamental aspects associated with quality of analytical data, such as sources of variation of analytical data, criteria for quality of

  17. Targeted physiotherapy for patellofemoral joint osteoarthritis: A protocol for a randomised, single-blind controlled trial

    Science.gov (United States)

    Crossley, Kay M; Vicenzino, Bill; Pandy, Marcus G; Schache, Anthony G; Hinman, Rana S

    2008-01-01

    Background The patellofemoral joint (PFJ) is one compartment of the knee that is frequently affected by osteoarthritis (OA) and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA. Methods 90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA) will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week) compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks). Physiotherapy treatment will consist of (i) quadriceps muscle retraining; (ii) quadriceps and hip muscle strengthening; (iii) patellar taping; (iv) manual PFJ and soft tissue mobilisation; and (v) OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction. Conclusion This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the potential to reduce

  18. Targeted physiotherapy for patellofemoral joint osteoarthritis: A protocol for a randomised, single-blind controlled trial

    Directory of Open Access Journals (Sweden)

    Schache Anthony G

    2008-09-01

    Full Text Available Abstract Background The patellofemoral joint (PFJ is one compartment of the knee that is frequently affected by osteoarthritis (OA and is a potent source of OA symptoms. However, there is a dearth of evidence for compartment-specific treatments for PFJ OA. Therefore, this project aims to evaluate whether a physiotherapy treatment, targeted to the PFJ, results in greater improvements in pain and physical function than a physiotherapy education intervention in people with symptomatic and radiographic PFJ OA. Methods 90 people with PFJ OA (PFJ-specific history, signs and symptoms and radiographic evidence of PFJ OA will be recruited from the community and randomly allocated into one of two treatments. A randomised controlled trial adhering to CONSORT guidelines will evaluate the efficacy of physiotherapy (8 individual sessions over 12 weeks, as well as a home exercise program 4 times/week compared to a physiotherapist-delivered OA education control treatment (8 individual sessions over 12 weeks. Physiotherapy treatment will consist of (i quadriceps muscle retraining; (ii quadriceps and hip muscle strengthening; (iii patellar taping; (iv manual PFJ and soft tissue mobilisation; and (v OA education. Resistance and dosage of exercises will be tailored to the participant's functional level and clinical state. Primary outcomes will be evaluated by a blinded examiner at baseline, 12 weeks and 9 months using validated and reliable pain, physical function and perceived global effect scales. All analyses will be conducted on an intention-to-treat basis using linear mixed regression models, including respective baseline scores as a covariate, subjects as a random effect, treatment condition as a fixed factor and the covariate by treatment interaction. Conclusion This RCT is targeting PFJ OA, an important sub-group of knee OA patients, with a specifically designed conservative intervention. The project's outcome will influence PFJ OA rehabilitation, with the

  19. Clinical pharmacists on medical care of pediatric inpatients: a single-center randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Chuan Zhang

    Full Text Available OBJECTIVE: To explore the best interventions and working patterns of clinical pharmacists in pediatrics and to determine the effectiveness of clinical pharmacists in pediatrics. METHODS: We conducted a randomized controlled trial of 160 pediatric patients with nerve system disease, respiratory system disease or digestive system disease, who were randomly allocated into two groups, with 80 in each group. Interventions by clinical pharmacists in the experimental group included answering questions of physicians and nurses, giving advice on treating patients, checking prescriptions and patient counseling at discharge. In the control group, patients were treated without clinical pharmacist interventions. RESULTS: Of the 109 interventions provided by clinical pharmacists during 4 months, 47 were consultations for physicians and nurses, 31 were suggestions of treatment, with 30 accepted by physicians (96.77% and 31 were medical errors found in 641 prescriptions. Five adverse drug reactions were submitted to the adverse drug reaction monitoring network, with three in the experimental group and two in the control group. The average length of stay (LOS for patients with respiratory system diseases in the experimental group was 6.45 days, in comparison with 10.83 days in the control group, which was statistically different (p value<0.05; Average drug compliance rate in the experimental group was 81.41%, in comparison with 70.17% of the control group, which was statistically different (p value<0.05. Cost of drugs and hospitalization and rate of readmission in two weeks after discharge in the two groups were not statistically different. CONCLUSION: Participation by clinical pharmacists in the pharmacotherapy of pediatric patients can reduce LOS of patients with respiratory system disease and improve compliance rate through discharge education, showing no significant effects on prevention of ADR, reduction of cost of drugs and hospitalization and readmission

  20. The Head Injury Retrieval Trial (HIRT): a single-centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics only

    Science.gov (United States)

    Garner, Alan A; Mann, Kristy P; Fearnside, Michael; Poynter, Elwyn; Gebski, Val

    2015-01-01

    Background Advanced prehospital interventions for severe brain injury remains controversial. No previous randomised trial has been conducted to evaluate additional physician intervention compared with paramedic only care. Methods Participants in this prospective, randomised controlled trial were adult patients with blunt trauma with either a scene GCS score <9 (original definition), or GCS<13 and an Abbreviated Injury Scale score for the head region ≥3 (modified definition). Patients were randomised to either standard ground paramedic treatment or standard treatment plus a physician arriving by helicopter. Patients were evaluated by 30-day mortality and 6-month Glasgow Outcome Scale (GOS) scores. Due to high non-compliance rates, both intention-to-treat and as-treated analyses were preplanned. Results 375 patients met the original definition, of which 197 was allocated to physician care. Differences in the 6-month GOS scores were not significant on intention-to-treat analysis (OR 1.11, 95% CI 0.74 to 1.66, p=0.62) nor was the 30-day mortality (OR 0.91, 95% CI 0.60 to 1.38, p=0.66). As-treated analysis showed a 16% reduction in 30-day mortality in those receiving additional physician care; 60/195 (29%) versus 81/180 (45%), p<0.01, Number needed to treat =6. 338 patients met the modified definition, of which 182 were allocated to physician care. The 6-month GOS scores were not significantly different on intention-to-treat analysis (OR 1.14, 95% CI 0.73 to 1.75, p=0.56) nor was the 30-day mortality (OR 1.05, 95% CI 0.66 to 1.66, p=0.84). As-treated analyses were also not significantly different. Conclusions This trial suggests a potential mortality reduction in patients with blunt trauma with GCS<9 receiving additional physician care (original definition only). Confirmatory studies which also address non-compliance issues are needed. Trial registration number NCT00112398. PMID:25795741

  1. Duct-to-mucosa versus dunking techniques of pancreaticojejunostomy after pancreaticoduodenectomy: Do we need more trials? A systematic review and meta-analysis with trial sequential analysis.

    Science.gov (United States)

    Kilambi, Ragini; Singh, Anand Narayan

    2018-03-25

    Pancreaticojejunostomy (PJ is the most widely used reconstruction technique after pancreaticoduodenectomy. Despite several randomized trials, the ideal technique of pancreaticojejunostomy remains debatable. We planned a meta-analysis of randomized trials comparing the two most common techniques of PJ (duct-to-mucosa and dunking) to identify the best available evidence in the current literature. We searched the Pubmed/Medline, Web of science, Science citation index, Google scholar and Cochrane Central Register of Controlled Trials electronic databases till October 2017 for all English language randomized trials comparing the two approaches. Statistical analysis was performed using Review Manager (RevMan), Version 5.3. Copenhagen: The Nordic Cochrane Center, The Cochrane Collaboration, 2014 and results were expressed as odds ratio for dichotomous and mean difference for continuous variables. P-value ≤ 0.05 was considered significant. Trial sequential analysis was performed using TSA version 0.9.5.5 (Copenhagen: The Copenhagen Trial Unit, Center for Clinical Intervention Research, 2016). A total of 8 trials were included, with a total of 1043 patients (DTM: 518; Dunking: 525). There was no significant difference between the two groups in terms of overall as well as clinically relevant POPF rate. Similarly, both groups were comparable for the secondary outcomes. Trial sequential analysis revealed that the required information size had been crossed without achieving a clinically significant difference for overall POPF; and though the required information size had not been achieved for CR-POPF, the current data has already crossed the futility line for CR-POPF with a 10% risk difference, 80% power and 5% α error. This meta-analysis found no significant difference between the two techniques in terms of overall and CR-POPF rates. Further, the existing evidence is sufficient to conclude lack of difference and further trials are unlikely to result in any change in the

  2. Revised analysis of singly ionized xenon, Xe II

    International Nuclear Information System (INIS)

    Hansen, J.E.; Persson, W.

    1987-01-01

    We present a revised analysis of the spectrum of singly ionized xenon, Xe II. This spectrum has been reanalyzed on the basis of the wavelength material published by Drs J. C. Boyce and C. J. Humphreys. The latter has kindly placed the original wavelength list covering the wavelength range 10220-390 A at our disposal. We report 161 energy levels which have been identified on the basis of classifications of 950 lines. We report first f and g levels in Xe II. Also a number of g-factors have been determined for the first time and we give in total 75 g-factors. We have carried out least-squares fits to the even configurations and report the resulting parameter values and eigenvector compositions. A least-squares fit to the 5p 4 6p configuration is also reported. The levels have been named in jK and for many levels also in LS coupling. The former is the better coupling scheme for Xe II. We present an analysis of the 5s photoelectron satellite spectrum of Xe based on our calculated eigenvector compositions and calculations of transition probabilities for ground state transitions as well as lifetimes for the 6p levels. The latter are compared to recent experimental measurements. A list of wavelengths for observed laser transitions showing the present classifications and a discussion of the determination of the ionization potential of Xe II concludes the paper. (orig.)

  3. A Prospective Randomized Clinical Trial of Single vs. Double Layer Closure of Hysterotomy at the Time of Cesarean Delivery: The Effect on Uterine Scar Thickness.

    Science.gov (United States)

    Bamberg, Christian; Dudenhausen, Joachim W; Bujak, Verena; Rodekamp, Elke; Brauer, Martin; Hinkson, Larry; Kalache, Karim; Henrich, Wolfgang

    2018-06-01

     We undertook a randomized clinical trial to examine the outcome of a single vs. a double layer uterine closure using ultrasound to assess uterine scar thickness.  Participating women were allocated to one of three uterotomy suture techniques: continuous single layer unlocked suturing, continuous locked single layer suturing, or double layer suturing. Transvaginal ultrasound of uterine scar thickness was performed 6 weeks and 6 - 24 months after Cesarean delivery. Sonographers were blinded to the closure technique.  An "intent-to-treat" and "as treated" ANOVA analysis included 435 patients (n = 149 single layer unlocked suturing, n = 157 single layer locked suturing, and n = 129 double layer suturing). 6 weeks postpartum, the median scar thickness did not differ among the three groups: 10.0 (8.5 - 12.3 mm) single layer unlocked vs. 10.1 (8.2 - 12.7 mm) single layer locked vs. 10.8 (8.1 - 12.8 mm) double layer; (p = 0.84). At the time of the second follow-up, the uterine scar was not significantly (p = 0.06) thicker if the uterus had been closed with a double layer closure 7.3 (5.7 - 9.1 mm), compared to single layer unlocked 6.4 (5.0 - 8.8 mm) or locked suturing techniques 6.8 (5.2 - 8.7 mm). Women who underwent primary or elective Cesarean delivery showed a significantly (p = 0.03, p = 0.02, "as treated") increased median scar thickness after double layer closure vs. single layer unlocked suture.  A double layer closure of the hysterotomy is associated with a thicker myometrium scar only in primary or elective Cesarean delivery patients. © Georg Thieme Verlag KG Stuttgart · New York.

  4. Treating Acute Insomnia: A Randomized Controlled Trial of a "Single-Shot" of Cognitive Behavioral Therapy for Insomnia.

    Science.gov (United States)

    Ellis, Jason G; Cushing, Toby; Germain, Anne

    2015-06-01

    Despite considerable evidence supporting cognitive behavioral therapy for insomnia (CBT-I) for chronic insomnia, it remains untested within the context of acute insomnia. This study examined the efficacy of a single session of CBT-I, with an accompanying self-help pamphlet, for individuals with acute insomnia. A pragmatic parallel group randomized controlled trial. Community. Forty adults (mean age 32.9 ± 13.72 y) with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defined insomnia disorder, except a self-reported duration of less than 3 mo (i.e., acute insomnia), who reported no previous exposure to CBT-I and were not currently taking medication for sleep. A single 60- to 70-min session of CBT-I (n = 20), with an accompanying self-help pamphlet, or wait list control group (n = 20). All subjects were offered a full individual course of CBT-I on completion of the study, regardless of group allocation. Subjects completed sleep diaries and the Insomnia Severity Index (ISI) pretreatment and 1 mo following treatment. There were no between-group differences on baseline ISI scores or subjective sleep continuity. The intervention group reported significantly lower ISI scores than controls (t(38) 2.24, P insomnia caseness (i.e., ≥ 10), 60% of those in the CBT-I group had remitted by 1 mo compared to 15% of those in the control group. This single session of cognitive behavioral therapy for insomnia (CBT-I) is sufficiently efficacious for a significant proportion of those with acute insomnia. The results are discussed in terms of integrating this brief form of CBT-I into the "stepped care" model of insomnia. Testing the efficacy of an early intervention for acute insomnia (SRCTN05891695) http://www.controlled-trials.com/ISRCTN05891695. © 2015 Associated Professional Sleep Societies, LLC.

  5. Intraoperative Radiation Using Low-Kilovoltage X-Rays for Early Breast Cancer: A Single Site Trial.

    Science.gov (United States)

    Silverstein, Melvin J; Epstein, Melinda S; Lin, Kevin; Chen, Peter; Khan, Sadia; Snyder, Lincoln; Guerra, Lisa E; De Leon, Cristina; Mackintosh, Ralph; Coleman, Colleen; Lopez, January; Kim, Brian

    2017-10-01

    Two prospective, randomized trials, TARGIT-A and ELIOT, have shown intraoperative radiation therapy (IORT) to be a safe alternative to whole breast radiation therapy following breast-conserving surgery for selected low-risk patients. However, minimal data are available about the clinical effectiveness of this modality of treatment using the Xoft ® Axxent ® Electronic Brachytherapy (eBx ® ) System ® . A total of 201 patients with 204 early-stage breast cancers were enrolled in a prospective X-ray IORT trial from June 2010 to September 2013. All tumors were treated with breast-conserving surgery and IORT. Data were collected at 1 week, 1 month, 6 months, 1 year, and yearly thereafter. With a median follow-up of 50 months, there have been seven ipsilateral breast tumor events (IBTE), no regional or distant recurrences, and no breast cancer-related deaths. One IBTE was within the IORT field, four outside of the IORT field but within the same quadrant as the index cancer, and two were new biologically different cancers in different quadrants. Three events were in patients who deviated from the protocol criteria. Kaplan-Meier analysis projects that 2.9% of patients will recur locally at 4 years. Recurrence rates observed in this trial were comparable to those of the TARGIT-A and ELIOT trials as well as the retrospective TARGIT-R trial. The low complication rates previously reported by our group as well as the low recurrence rates reported in this study support the cautious use and continued study of IORT in selected women with low-risk breast cancer.

  6. Anterior single implants with different neck designs : 5 Year results of a randomized clinical trial

    NARCIS (Netherlands)

    den Hartog, Laurens; Meijer, Henny J A; Vissink, Arjan; Raghoebar, Gerry M

    BACKGROUND: The design of the implant neck might be significant for preservation of marginal bone. PURPOSE: To compare the 5-year radiographic and clinical outcome of single anterior implants provided with a smooth neck, a rough neck or a scalloped rough neck. MATERIALS AND METHODS: 93 Patients with

  7. Detection and Characterization of Single-Trial fMRI BOLD Responses : Paradigm Free Mapping

    NARCIS (Netherlands)

    Gaudes, Cesar Caballero; Petridou, Natalia; Dryden, Ian L.; Bai, Li; Francis, Susan T.; Gowland, Penny A.

    This work presents a novel method of mapping the brain's response to single stimuli in space and time without prior knowledge of the paradigm timing: paradigm free mapping (PFM). This method is based on deconvolution of the hemodynamic response from the voxel time series assuming a linear response

  8. Immediate non-occlusal loading of single implants in the aesthetic zone : A randomized clinical trial

    NARCIS (Netherlands)

    den Hartog, Laurens; Raghoebar, Gerry M.; Stellingsma, Kees; Vissink, Arjan; Meijer, Henny J. A.

    P>Aim This study compared the outcome of immediate non-occlusal loading with conventional loading for single implants in the maxillary aesthetic zone. It was hypothesized that immediate non-occlusal loading is not inferior to conventional loading. Materials and Methods Sixty-two patients with a

  9. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial): A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea

    Science.gov (United States)

    Sissoko, Daouda; Laouenan, Cedric; Folkesson, Elin; M’Lebing, Abdoul-Bing; Beavogui, Abdoul-Habib; Baize, Sylvain; Camara, Alseny-Modet; Maes, Piet; Shepherd, Susan; Danel, Christine; Carazo, Sara; Conde, Mamoudou N.; Gala, Jean-Luc; Colin, Géraldine; Savini, Hélène; Bore, Joseph Akoi; Le Marcis, Frederic; Koundouno, Fara Raymond; Petitjean, Frédéric; Lamah, Marie-Claire; Diederich, Sandra; Tounkara, Alexis; Poelart, Geertrui; Berbain, Emmanuel; Dindart, Jean-Michel; Duraffour, Sophie; Lefevre, Annabelle; Leno, Tamba; Peyrouset, Olivier; Irenge, Léonid; Bangoura, N’Famara; Palich, Romain; Hinzmann, Julia; Kraus, Annette; Barry, Thierno Sadou; Berette, Sakoba; Bongono, André; Camara, Mohamed Seto; Chanfreau Munoz, Valérie; Doumbouya, Lanciné; Souley Harouna; Kighoma, Patient Mumbere; Koundouno, Fara Roger; Réné Lolamou; Loua, Cécé Moriba; Massala, Vincent; Moumouni, Kinda; Provost, Célia; Samake, Nenefing; Sekou, Conde; Soumah, Abdoulaye; Arnould, Isabelle; Komano, Michel Saa; Gustin, Lina; Berutto, Carlotta; Camara, Diarra; Camara, Fodé Saydou; Colpaert, Joliene; Delamou, Léontine; Jansson, Lena; Kourouma, Etienne; Loua, Maurice; Malme, Kristian; Manfrin, Emma; Maomou, André; Milinouno, Adele; Ombelet, Sien; Sidiboun, Aboubacar Youla; Verreckt, Isabelle; Yombouno, Pauline; Bocquin, Anne; Carbonnelle, Caroline; Carmoi, Thierry; Frange, Pierre; Mely, Stéphane; Nguyen, Vinh-Kim; Pannetier, Delphine; Taburet, Anne-Marie; Treluyer, Jean-Marc; Kolie, Jacques; Moh, Raoul; Gonzalez, Minerva Cervantes; Kuisma, Eeva; Liedigk, Britta; Ngabo, Didier; Rudolf, Martin; Thom, Ruth; Kerber, Romy; Gabriel, Martin; Di Caro, Antonino; Wölfel, Roman; Badir, Jamal; Bentahir, Mostafa; Deccache, Yann; Dumont, Catherine; Durant, Jean-François; El Bakkouri, Karim; Gasasira Uwamahoro, Marie; Smits, Benjamin; Toufik, Nora; Van Cauwenberghe, Stéphane; Ezzedine, Khaled; Dortenzio, Eric; Pizarro, Louis; Etienne, Aurélie; Guedj, Jérémie; Fizet, Alexandra; Barte de Sainte Fare, Eric; Murgue, Bernadette; Tran-Minh, Tuan; Rapp, Christophe; Piguet, Pascal; Poncin, Marc; Draguez, Bertrand; Allaford Duverger, Thierry; Barbe, Solenne; Baret, Guillaume; Defourny, Isabelle; Carroll, Miles; Raoul, Hervé; Augier, Augustin; Eholie, Serge P.; Yazdanpanah, Yazdan; Levy-Marchal, Claire; Antierrens, Annick; Van Herp, Michel; Günther, Stephan; de Lamballerie, Xavier; Keïta, Sakoba; Mentre, France

    2016-01-01

    , day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively). Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14%) and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%). In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated. Conclusions In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches

  10. Single-cell analysis of targeted transcriptome predicts drug sensitivity of single cells within human myeloma tumors.

    Science.gov (United States)

    Mitra, A K; Mukherjee, U K; Harding, T; Jang, J S; Stessman, H; Li, Y; Abyzov, A; Jen, J; Kumar, S; Rajkumar, V; Van Ness, B

    2016-05-01

    Multiple myeloma (MM) is characterized by significant genetic diversity at subclonal levels that have a defining role in the heterogeneity of tumor progression, clinical aggressiveness and drug sensitivity. Although genome profiling studies have demonstrated heterogeneity in subclonal architecture that may ultimately lead to relapse, a gene expression-based prediction program that can identify, distinguish and quantify drug response in sub-populations within a bulk population of myeloma cells is lacking. In this study, we performed targeted transcriptome analysis on 528 pre-treatment single cells from 11 myeloma cell lines and 418 single cells from 8 drug-naïve MM patients, followed by intensive bioinformatics and statistical analysis for prediction of proteasome inhibitor sensitivity in individual cells. Using our previously reported drug response gene expression profile signature at the single-cell level, we developed an R Statistical analysis package available at https://github.com/bvnlabSCATTome, SCATTome (single-cell analysis of targeted transcriptome), that restructures the data obtained from Fluidigm single-cell quantitative real-time-PCR analysis run, filters missing data, performs scaling of filtered data, builds classification models and predicts drug response of individual cells based on targeted transcriptome using an assortment of machine learning methods. Application of SCATT should contribute to clinically relevant analysis of intratumor heterogeneity, and better inform drug choices based on subclonal cellular responses.

  11. Geochemistry of single diamond crystals by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Damarupurshad, A.

    1995-02-01

    Neutron activation analysis is probably the most powerful technique, available to date, for the analysis of the trace elements in diamond. In this study the technique of neutron activation analysis has been modified and optimized for the analysis of single, small (0.01-0.5 carat), inclusion-bearing and inclusion-free diamonds. Instrumental neutron activation analysis was used to analyze for up to 40 different elements at the ppb and ppt levels in diamonds from Brazil, South Africa, Colorado and China. The data obtained was used to detect and understand the differences between diamonds from the eclogitic and peridotitic para geneses and between diamonds from the different localities. In this regard, two inter element ratios, i.e. Cr/Sc and Au/Ir ratios were found to be useful. It seems that diamonds from a particular locality or mine have a unique range of Cr/Sc ratios. Furthermore, the identity of the dominant silicate inclusion(s) can be deduced from the Cr/Sc ratio of the diamond, since each type of silicate inclusion has a different range of Cr/Sc ratios. Not only is the Cr/Sc ratio distinctive for silicate inclusions in diamonds, it is also distinctive for minerals co genetic with diamond, such as orange garnet, red garnet, chrome diopside and ortho pyroxene (macrocrysts) which were separated from kimberlites. Sulphide inclusions may also contain detectable quantities of Au and Ir and the ratios of these two elements can also be used to differentiate between diamonds of the two para geneses. Carbon isotope ratios of these eclogitic and peridotitic diamonds were also measured. The comparison of this with the Cr/Sc ratios revealed that the carbon isotope ratios of both para geneses overlap in a narrow range and do not show the clear separations seen with Cr/Sc and Au/Ir ratios. It can be suggested, therefore, on the basis of the suite of 61 diamonds analyzed in this study, that the Cr/Sc and Au/Ir ratios are much more useful tools to distinguish between diamonds

  12. Clinical trials of homoeopathy.

    Science.gov (United States)

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  13. Going single but not solo with podocytes: potentials, limitations, and pitfalls of single-cell analysis.

    Science.gov (United States)

    Schiffer, Mario

    2017-11-01

    Single-cell RNA-sequence (RNA-seq) is a widely used tool to study biological questions in single cells. The discussed study identified 92 genes being predominantly expressed in podocytes based on a 5-fold higher expression compared with endothelial and mesangial cells. In addition to technical pitfalls, the question that is discussed in this commentary is whether results of a single-cell RNAseq study are able to deliver expression data that truly characterize a podocyte. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Qualitative data collection and analysis methods: the INSTINCT trial.

    Science.gov (United States)

    Meurer, William J; Frederiksen, Shirley M; Majersik, Jennifer J; Zhang, Lingling; Sandretto, Annette; Scott, Phillip A

    2007-11-01

    Patient care practices often lag behind current scientific evidence and professional guidelines. The failure of such knowledge translation (KT) efforts may reflect inadequate assessment and management of specific barriers confronting both physicians and patients at the point of treatment level. Effective KT in this setting may benefit from the use of qualitative methods to identify and overcome these barriers. Qualitative methodology allows in-depth exploration of the barriers involved in adopting practice change and has been infrequently used in emergency medicine research. The authors describe the methodology for qualitative analysis within the INcreasing Stroke Treatment through INteractive behavioral Change Tactics (INSTINCT) trial. This includes processes for valid data collection and reliable analysis of the textual data from focus group and interview transcripts. INSTINCT is a 24-hospital, randomized, controlled study that is designed to evaluate a system-based barrier assessment and interactive educational intervention to increase appropriate tissue plasminogen activator (tPA) use in ischemic stroke. Intervention hospitals undergo baseline barrier assessment using both qualitative as well as quantitative (survey) techniques. Investigators obtain data on local barriers to tPA use, as well as information on local attitudes, knowledge, and beliefs regarding acute stroke treatment. Targeted groups at each site include emergency physicians, emergency nurses, neurologists, radiologists, and hospital administrators. Transcript analysis using NVivo7 with a predefined barrier taxonomy is described. This will provide both qualitative insight on thrombolytic use and importance of specific barrier types for each site. The qualitative findings subsequently direct the form of professional education efforts and system interventions at treatment sites.

  15. Experimental Treatment with Favipiravir for Ebola Virus Disease (the JIKI Trial: A Historically Controlled, Single-Arm Proof-of-Concept Trial in Guinea.

    Directory of Open Access Journals (Sweden)

    Daouda Sissoko

    2016-03-01

    of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter. Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A "target value" of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis. Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12. Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20, and 44 had a baseline Ct value < 20 (Group A Ct < 20. Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%-32.4% in Group A Ct ≥ 20 and 91% (95% CI 78.8%-91.1% in Group A Ct < 20. Both mortality 95% CIs included the predefined target value (30% and 85%, respectively. Baseline serum creatinine was ≥110 μmol/l in 48% of patients in Group A Ct ≥ 20 (≥300 μmol/l in 14% and in 90% of patients in Group A Ct < 20 (≥300 μmol/l in 44%. In Group A Ct ≥ 20, 17% of patients with baseline creatinine ≥110 μmol/l died, versus 97% in Group A Ct < 20. In patients who survived, the mean decrease in viral load was 0.33 log10 copies/ml per day of follow-up. RNA viral load values and mortality were not significantly different between adults starting favipiravir within <72 h of symptoms compared to others. Favipiravir was well tolerated.In the context of an outbreak at its peak, with crowded care centers, randomizing patients to receive either standard care or standard care plus an experimental drug was not felt to be appropriate. We did a non-randomized trial. This trial reaches nuanced conclusions. On the one hand, we do not

  16. Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial.

    Science.gov (United States)

    Faurholt-Jepsen, M; Frost, M; Ritz, C; Christensen, E M; Jacoby, A S; Mikkelsen, R L; Knorr, U; Bardram, J E; Vinberg, M; Kessing, L V

    2015-10-01

    The number of studies on electronic self-monitoring in affective disorder and other psychiatric disorders is increasing and indicates high patient acceptance and adherence. Nevertheless, the effect of electronic self-monitoring in patients with bipolar disorder has never been investigated in a randomized controlled trial (RCT). The objective of this trial was to investigate in a RCT whether the use of daily electronic self-monitoring using smartphones reduces depressive and manic symptoms in patients with bipolar disorder. A total of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60 years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young Mania Rating Scale (YMRS) scores ≤17 were randomized to the use of a smartphone for daily self-monitoring including a clinical feedback loop (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for 6 months. The primary outcomes were differences in depressive and manic symptoms measured using HAMD-17 and YMRS, respectively, between the intervention and control groups. Intention-to-treat analyses using linear mixed models showed no significant effects of daily self-monitoring using smartphones on depressive as well as manic symptoms. There was a tendency towards more sustained depressive symptoms in the intervention group (B = 2.02, 95% confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients without mixed symptoms and patients with presence of depressive and manic symptoms showed significantly more depressive symptoms and fewer manic symptoms during the trial period in the intervention group. These results highlight that electronic self-monitoring, although intuitive and appealing, needs critical consideration and further clarification before it is implemented as a clinical tool.

  17. Analysis of the Single Toggle Jaw Crusher Force Transmission Characteristics

    Directory of Open Access Journals (Sweden)

    Moses Frank Oduori

    2016-01-01

    Full Text Available This paper sets out to perform a static force analysis of the single toggle jaw crusher mechanism and to obtain the force transmission characteristics of the mechanism. In order to obtain force transmission metrics that are characteristic of the structure of the mechanism, such influences as friction, dead weight, and inertia are considered to be extraneous and neglected. Equations are obtained by considering the balance of forces at the moving joints and appropriately relating these to the input torque and the output torque. A mechanical advantage, the corresponding transmitted torque, and the variations thereof, during the cycle of motion of the mechanism, are obtained. The mechanical advantage that characterizes the mechanism is calculated as the mean value over the active crushing stroke of the mechanism. The force transmission characteristics can be used as criteria for the comparison of different jaw crusher mechanism designs in order to select the most suitable design for a given application. The equations obtained can also be used in estimating the forces sustained by the components of the mechanism.

  18. "Straight Talk" for African-American heterosexual men: results of a single-arm behavioral intervention trial.

    Science.gov (United States)

    Frye, Victoria; Henny, Kirk; Bonner, Sebastian; Williams, Kim; Bond, Keosha T; Hoover, Donald R; Lucy, Debbie; Greene, Emily; Koblin, Beryl A

    2013-01-01

    In the United States, heterosexual transmission is the second leading cause of HIV/AIDS, and two-thirds of all heterosexually acquired cases diagnosed between 2005 and 2008 occurred among African-Americans. Few HIV prevention interventions have been designed specifically for African-American heterosexual men not seeking clinical treatment. Here we report results of a single-arm intervention trial of a theory-based HIV prevention intervention designed to increase condom use, reduce concurrent partnering and increase HIV testing among heterosexually active African-American men living in high HIV prevalence areas of New York City. We tested our hypothesis using McNemar discordant pairs exact test for binary variables and paired t-tests for continuous variables. We observed statistically significant declines in mean number of total and new female partners, unprotected sex partners, and partner concurrency in both primary and nonprimary sex partnerships between baseline and 3 months postintervention.

  19. Generalisability of an online randomised controlled trial: an empirical analysis.

    Science.gov (United States)

    Wang, Cheng; Mollan, Katie R; Hudgens, Michael G; Tucker, Joseph D; Zheng, Heping; Tang, Weiming; Ling, Li

    2018-02-01

    Investigators increasingly use online methods to recruit participants for randomised controlled trials (RCTs). However, the extent to which participants recruited online represent populations of interest is unknown. We evaluated how generalisable an online RCT sample is to men who have sex with men in China. Inverse probability of sampling weights (IPSW) and the G-formula were used to examine the generalisability of an online RCT using model-based approaches. Online RCT data and national cross-sectional study data from China were analysed to illustrate the process of quantitatively assessing generalisability. The RCT (identifier NCT02248558) randomly assigned participants to a crowdsourced or health marketing video for promotion of HIV testing. The primary outcome was self-reported HIV testing within 4 weeks, with a non-inferiority margin of -3%. In the original online RCT analysis, the estimated difference in proportions of HIV tested between the two arms (crowdsourcing and health marketing) was 2.1% (95% CI, -5.4% to 9.7%). The hypothesis that the crowdsourced video was not inferior to the health marketing video to promote HIV testing was not demonstrated. The IPSW and G-formula estimated differences were -2.6% (95% CI, -14.2 to 8.9) and 2.7% (95% CI, -10.7 to 16.2), with both approaches also not establishing non-inferiority. Conducting generalisability analysis of an online RCT is feasible. Examining the generalisability of online RCTs is an important step before an intervention is scaled up. NCT02248558. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Evaluation of wound healing in diabetic foot ulcer using platelet-rich plasma gel: A single-arm clinical trial.

    Science.gov (United States)

    Mohammadi, Mohammad Hossein; Molavi, Behnam; Mohammadi, Saeed; Nikbakht, Mohsen; Mohammadi, Ashraf Malek; Mostafaei, Shayan; Norooznezhad, Amir Hossein; Ghorbani Abdegah, Ali; Ghavamzadeh, Ardeshir

    2017-04-01

    The aim of the present study was to evaluate the effectiveness of using autologous platelet-rich plasma (PRP) gel for treatment of diabetic foot ulcer (DFU) during the first 4 weeks of the treatment. In this longitudinal and single-arm trial, 100 patients were randomly selected after meeting certain inclusion and exclusion criteria; of these 100 patients, 70 (70%) were enrolled in the trial. After the primary care actions such as wound debridement, the area of each wound was calculated and recorded. The PRP therapy (2mL/cm 2 of ulcers) was performed weekly until the healing time for each patient. We used one sample T-test for healing wounds and Bootstrap resampling approach for reporting confidence interval with 1000 Bootstrap samples. The p-valuehealing time was 8.7, 8 weeks (SD: 3.93) except for 2 mentioned cases. According to one sample T-test, wound area (cm 2 ), on average, significantly decreased to 51.9% (CI: 46.7-57.1) through the first four weeks of therapy. Furthermore, significant correlation (0.22) was not found between area of ulcers and healing duration (p-value>0.5). According to the results, PRP could be considered as a candidate treatment for non-healing DFUs as it may prevent future complications such as amputation or death in this pathological phenomenon. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.

    Science.gov (United States)

    Hooten, W Michael; Warner, David O

    2015-03-01

    The objectives of this randomized, single-blinded, placebo-controlled pilot trial were to investigate the effects of varenicline on opioid withdrawal among chronic pain patients undergoing opioid detoxification in an interdisciplinary pain program and the feasibility of varenicline use in this population. Twenty-one patients were recruited (varenicline=10, placebo=11), and 7 patients in the varenicline and 11 in the placebo group completed the study. Opioid withdrawal was quantified using the Clinical Opiate Withdrawal Scale, and varenicline-related adverse effects were assessed. Opioid withdrawal scores tended to decrease over the course of opioid tapering in those receiving varenicline and increase in those receiving placebo. Varenicline was well-tolerated in this population, with no adverse drug effects (including nausea) observed and no effect on improvements in pain severity and depression. This randomized pilot study provides preliminary data for future trials of varenicline in opioid-dependent adults with chronic pain undergoing medically directed opioid detoxification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Evaluating Study Withdrawal Among Biologics and Immunomodulators in Treating Ulcerative Colitis: A Meta-analysis of Controlled Clinical Trials.

    Science.gov (United States)

    Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

    2016-04-01

    We conducted a systematic review and meta-analysis to evaluate the efficacy and adverse event (AE)-associated tolerability of treatment with immunomodulators and biologics in ulcerative colitis clinical trials. We performed a literature search of PubMed and the Cochrane databases to identify randomized placebo-controlled trials of immunomodulators and biologics. Tolerability was defined through study withdrawal due to AEs and efficacy through clinical response in induction trials and clinical remission in maintenance trials. We performed meta-analyses using a random-effects model to determine relative risks (RRs) of efficacy and study withdrawal. Number needed to treat (NNT) and number needed to stop (NNS) were determined. The ratio of NNS/NNT was calculated, with a higher ratio indicating a greater number of patients in remission for every AE study discontinuation. We examined 13 single-agent trials representing biologics (infliximab, adalimumab, golimumab, and vedolizumab) and immunomodulators (tacrolimus and azathioprine). Induction therapy did not result in excess study withdrawal with immunomodulators (RR = 0.9, 95% CI 0.1-12.0) or biologics (RR = 0.7, 95% CI 0.3-1.8), therefore the NNS/NNT ratio could not be assessed because of high tolerability. Maintenance immunomodulator therapy resulted in a NNS of 14 (RR = 2.8, 95% CI 0.7-10.5) and NNS/NNT ratio of 2.4 in 2 trials. Biologics did not result in excess study withdrawal in maintenance (RR = 0.7, 95% CI 0.3-1.7) or combined induction-and-maintenance (RR = 0.6, 95% CI 0.4-1.0) trials. Biologics were not associated with a higher RR of study withdrawal due to AE than placebo. There were insufficient data to compare these results with immunomodulators.

  3. The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants.

    Science.gov (United States)

    Meah, Farah A; DiMeglio, Linda A; Greenbaum, Carla J; Blum, Janice S; Sosenko, Jay M; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella

    2016-06-01

    The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.

  4. Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.

    Science.gov (United States)

    Wirsich, Jonathan; Bénar, Christian; Ranjeva, Jean-Philippe; Descoins, Médéric; Soulier, Elisabeth; Le Troter, Arnaud; Confort-Gouny, Sylviane; Liégeois-Chauvel, Catherine; Guye, Maxime

    2014-10-15

    Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. RoboSCell: An automated single cell arraying and analysis instrument

    KAUST Repository

    Sakaki, Kelly; Foulds, Ian G.; Liu, William; Dechev, Nikolai; Burke, Robert Douglas; Park, Edward

    2009-01-01

    Single cell research has the potential to revolutionize experimental methods in biomedical sciences and contribute to clinical practices. Recent studies suggest analysis of single cells reveals novel features of intracellular processes, cell-to-cell

  6. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

    Directory of Open Access Journals (Sweden)

    Leonore Lovis

    Full Text Available BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45 or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45. Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI: 56.6-88.5% and 80.8% (95% CI: 60.6-93.4% for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60. O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4% and 96.6% (95% CI: not defined, respectively (P = 0.009. Egg reduction rates (ERRs against O. viverrini were very high for both doses (>99%, but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1% and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment. Adverse events were common (96%, mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled-Trials

  7. Combined Acupuncture and Auriculotherapy in Burning Mouth Syndrome Treatment: A Preliminary Single-Arm Clinical Trial.

    Science.gov (United States)

    Franco, Faraína Rodrigues Vasconcelos; Castro, Luciano Alberto; Borsatto, Maria Cristina; Silveira, Erika Aparecida; Ribeiro-Rotta, Rejane Faria

    2017-02-01

    Burning mouth syndrome (BMS) is a chronic pain disorder that is difficult to diagnose and refractory to treatment; it is more prevalent in pre- and postmenopausal women. Acupuncture and auriculotherapy have been suggested as options for the treatment of pain because they promote analgesia and allow for the reduction of symptoms with lower doses of drugs; this leads to greater patient compliance with treatment and has a positive effect on quality of life. Clinical trials investigating the effectiveness of acupuncture in the treatment of BMS are scarce in the literature. To investigate the effect of combined acupuncture and auriculotherapy on pain management and quality of life in patients with BMS. Sixty patients with BMS were subjected to a thorough differential diagnosis. Of these, 12 met the inclusion criteria and agreed to participate. Eight patients completed treatment with acupuncture and auriculotherapy using a previously established protocol. The outcome variables were analyzed before and after treatment: pain/burning (visual analog scale; VAS), salivary flow (unstimulated sialometry), and quality of life (Short-Form Oral Health Impact Profile [OHIP-14]). Two-year follow-up was carried out by assessing VAS and OHIP-14. The intensity of pain/burning decreased significantly after the first treatment sessions, as shown by low values on the VAS (0-2) and a subjective indicator of quality of life (mean = 5.37 ± 3.50). There was no relationship between salivary flow and the intensity of pain/burning. At 2-year follow-up, no statistically significant difference was observed for VAS, but improvement on OHIP-14 was seen. Combined acupuncture/auriculotherapy was effective in reducing the intensity of burning and improving quality of life. There was no relationship between salivary flow and the intensity of burning mouth. Patients' status improved after acupuncture and auriculotherapy at 2-year follow-up.

  8. A pragmatic randomised multi-centre trial of multifamily and single family therapy for adolescent anorexia nervosa.

    Science.gov (United States)

    Eisler, Ivan; Simic, Mima; Hodsoll, John; Asen, Eia; Berelowitz, Mark; Connan, Frances; Ellis, Gladys; Hugo, Pippa; Schmidt, Ulrike; Treasure, Janet; Yi, Irene; Landau, Sabine

    2016-11-24

    Considerable progress has been made in recent years in developing effective treatments for child and adolescent anorexia nervosa, with a general consensus in the field that eating disorders focussed family therapy (often referred to as Maudsley Family Therapy or Family Based Treatment) currently offers the most promising outcomes. Nevertheless, a significant number do not respond well and additional treatment developments are needed to improve outcomes. Multifamily therapy is a promising treatment that has attracted considerable interest and we report the results of the first randomised controlled trial of multifamily therapy for adolescent anorexia nervosa. The study was a pragmatic multicentre randomised controlled superiority trial comparing two outpatient eating disorder focussed family interventions - multifamily therapy (MFT-AN) and single family therapy (FT-AN). A total of 169 adolescents with a DSM-IV diagnosis of anorexia nervosa or eating disorder not otherwise specified (restricting type) were randomised to the two treatments using computer generated blocks of random sizes to ensure balanced numbers in the trial arms. Independent assessors, blind to the allocation, completed evaluations at baseline, 3 months, 12 months (end of treatment) and 18 months. Both treatment groups showed clinically significant improvements with just under 60% achieving a good or intermediate outcome (on the Morgan-Russell scales) at the end of treatment in the FT-AN group and more than 75% in the MFT-AN group - a statistically significant benefit in favour of the multifamily intervention (OR = 2.55 95%; CI 1.17, 5.52; p = 0.019). At follow-up (18 months post baseline) there was relatively little change compared to end of treatment although the difference in primary outcome between the treatments was no longer statistically significant. Clinically significant gains in weight were accompanied by improvements in mood and eating disorder psychopathology. Approximately

  9. Conditional analysis of mixed Poisson processes with baseline counts: implications for trial design and analysis.

    Science.gov (United States)

    Cook, Richard J; Wei, Wei

    2003-07-01

    The design of clinical trials is typically based on marginal comparisons of a primary response under two or more treatments. The considerable gains in efficiency afforded by models conditional on one or more baseline responses has been extensively studied for Gaussian models. The purpose of this article is to present methods for the design and analysis of clinical trials in which the response is a count or a point process, and a corresponding baseline count is available prior to randomization. The methods are based on a conditional negative binomial model for the response given the baseline count and can be used to examine the effect of introducing selection criteria on power and sample size requirements. We show that designs based on this approach are more efficient than those proposed by McMahon et al. (1994).

  10. Efficacy of single buccal infiltrations for maxillary first molars in patients with irreversible pulpitis: a randomized controlled clinical trial.

    Science.gov (United States)

    Atasoy Ulusoy, Ö İ; Alaçam, T

    2014-03-01

    To evaluate the efficacy of a single buccal infitration using 4% articaine hydrochloride (HCl) with 1 : 100,000 epinephrine or 4% articaine HCl with 1 : 100 000 epinephrine bitartrate for obtaining adequate pulpal anaesthesia in the palatal roots of maxillary first molars associated with irreversible pulpitis. In this single-blind randomized clinical trial, fifty subjects were randomly allocated to receive maxillary buccal injections of 1.5 mL 4% articaine with 1 : 100,000 epinephrine (n = 25) or 1.5 mL 4% articaine with 1 : 100,000 epinephrine bitartrate (n = 25). Visual analogue scale (VAS) scores and pulse rate measurements were recorded during access cavity preparation and initial file placement into the mesiobuccal, distobuccal and palatal canals. Data were analysed using Duncan and t-tests. There was no significant difference between the two anaesthetic solutions regarding the VAS scores and pulse rate measurements during endodontic procedures. The mean VAS ratings of the 50 patients during file placement into the palatal canals were significantly higher compared with the other three root canal procedures (P pulpitis. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  11. Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial.

    Science.gov (United States)

    Fujiwara, Takashi; Nishida, Naoya; Nota, Jumpei; Kitani, Takashi; Aoishi, Kunihide; Takahashi, Hirotaka; Sugahara, Takuya; Hato, Naohito

    2016-12-01

    Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.

  12. Field trial of a fast single-pass transmit-receive probe during Gentilly II steam generator tube inspection

    International Nuclear Information System (INIS)

    Obrutsky, L.; Cantin, M.; Renaud, J.; Cecco, V.; Lakhan, R.; Sullivan, S.

    2000-01-01

    A new generation of transmit-receive single-pass probes, denoted as C6 or X probe, was field tested during the Gentilly II, 2000 steam generator tube inspection. This probe has a performance equivalent to rotating probes and can be used for tubesheet and full-length inspection at an inspection speed equivalent to that of bobbin probes. Existing C3 transmit-receive probes have been demonstrated to be effective in detecting circumferential cracks. The C5 probe can detect both circumferential and axial cracks and volumetric defects but cannot discriminate between them. The C6 probe expands on the capabilities of both probes in a single probe head. It can simultaneously detect and discriminate between circumferential and axial cracks to satisfy different plugging criteria. It has excellent coverage, good defect detectability, and improved sizing and characterization. Probe data is displayed in C-scan format so that the amount of data to be analyzed is similar to rotating probes. The C6 probe will significantly decrease inspection time and the need for re-inspection and tube pulling. This paper describes the advantages of the probe and demonstrates its capabilities employing signals from tube samples with calibration flaws and laboratory induced cracks. It shows the results from the field trial of the probe at Gentilly II and describes the instrumentation, hardware and software used for the inspection. (author)

  13. Field trial of a fast single-pass transmit-receive probe during Gentilly II steam generator tube inspection

    International Nuclear Information System (INIS)

    Obrutsky, L.; Cantin, M.; Renaud, J.; Cecco, V.; Lakhan, R.; Sullivan, S.

    2000-01-01

    A new generation of transmit-receive single-pass probes, denoted as C6 or X probe, was field-tested during the Gentilly II, 2000 steam generator tube inspection. This probe has a performance equivalent to rotating probes and can be used for tubesheet and full-length inspection at an inspection speed equivalent to that of bobbin probes. Existing C3 transmit-receive probes have been demonstrated to be effective in detecting circumferential cracks. The C5 probe can detect both circumferential and axial cracks and volumetric defects but cannot discriminate between them. The C6 probe expands on the capabilities of both probes in a single probe head. It can simultaneously detect and discriminate between circumferential and axial cracks to satisfy different plugging criteria. It has excellent coverage, good defect detectability, and improved sizing and characterization. Probe data is displayed in C-scan format so that the amount of data to be analyzed is similar to rotating probes. The C6 probe will significantly decrease inspection time and the need for re-inspection and tube pulling. This paper describes the advantages of the probe and demonstrates its capabilities employing signals from tube samples with calibration flaws and laboratory induced cracks. It shows the results from the field trial of the probe at Gentilly II and describes the instrumentation, hardware and software used for the inspection. (author)

  14. Different materials for direct pulp capping: systematic review and meta-analysis and trial sequential analysis.

    Science.gov (United States)

    Schwendicke, Falk; Brouwer, Fredrik; Schwendicke, Anja; Paris, Sebastian

    2016-07-01

    We systematically assessed randomized controlled trials comparing direct pulp capping materials. Trials comparing materials for direct capping and evaluating clinically and/or radiographically determined success after minimum 3 months were included. Two reviewers independently screened electronic databases (Medline, Central, Embase) and performed hand searches. Risk of bias was assessed and meta-analyses were performed, separated for dentition. Trial sequential analysis was used to assess risk of random errors. Strength of evidence was graded using the GRADE approach. From a total of 453 identified studies, 11 (all with high risk of bias) investigating 1094 teeth (922 patients) were included. Six studies were on primary teeth (all with carious exposures) and five on permanent teeth (carious and artificial exposures). Mean follow-up was 14 months (range 3-24). Most studies used calcium hydroxide as control, comparing it to mineral trioxide aggregate (MTA) (three studies), bonding without prior etching/conditioning (two), or bonding with prior etching/conditioning, enamel matrix proteins, resin-modified glass ionomer cement, calcium sulfate, zinc oxide eugenol, corticosteroids, antibiotics, or formocresol (each in only one study). One study compared MTA and calcium-enriched cement. In permanent teeth, risk of failure was significantly decreased if MTA instead of calcium hydroxide was used (risk ratio (RR) [95 % confidence intervals (CI)] 0.59 [0.39/0.90]); no difference was found for primary teeth. Other comparisons did not find significant differences or were supported by only one study. No firm evidence was reached according to trial sequential analysis. There is insufficient data to recommend or refute the use of a specific material. More long-term practice-based studies with real-life exposures are required. To reduce risk of failure, dentists might consider using MTA instead of calcium hydroxide (CH) for direct capping. Current evidence is insufficient for

  15. Effect of Metformin on Plasma Fibrinogen Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

    Science.gov (United States)

    Simental-Mendia, Luis E; Pirro, Matteo; Atkin, Stephen L; Banach, Maciej; Mikhailidis, Dimitri P; Sahebkar, Amirhossein

    2018-01-01

    Fibrinogen is a key mediator of thrombosis and it has been implicated in the pathogenesis of atherosclerosis. Because metformin has shown a potential protective effect on different atherothrombotic risk factors, we assessed in this meta-analysis its effect on plasma fibrinogen concentrations. A systematic review and meta-analysis was carried out to identify randomized placebo-controlled trials evaluating the effect of metformin administration on fibrinogen levels. The search included PubMed-Medline, Scopus, ISI Web of Knowledge and Google Scholar databases (by June 2, 2017) and quality of studies was performed according to Cochrane criteria. Quantitative data synthesis was conducted using a random-effects model and sensitivity analysis by the leave-one-out method. Meta-regression analysis was performed to assess the modifiers of treatment response. Meta-analysis of data from 9 randomized placebo-controlled clinical trials with 2302 patients comprising 10 treatment arms did not suggest a significant change in plasma fibrinogen concentrations following metformin therapy (WMD: -0.25 g/L, 95% CI: -0.53, 0.04, p = 0.092). The effect size was robust in the leave-one-out sensitivity analysis and remained non-significant after omission of each single study from the meta-analysis. No significant effect of metformin on plasma fibrinogen concentrations was demonstrated in the current meta-analysis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Bone metastasis: review and critical analysis of random allocation trials of local field treatment

    International Nuclear Information System (INIS)

    Ratanatharathorn, Vaneerat; Powers, William E.; Moss, William T.; Perez, Carlos A.

    1999-01-01

    Purpose: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. Methods and Materials: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. Results: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment. All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is 'informative' (the processes of loss relate to the outcome) and not acceptable since it

  17. One-trial spatial learning: wild hummingbirds relocate a reward after a single visit.

    Science.gov (United States)

    Flores-Abreu, I Nuri; Hurly, T Andrew; Healy, Susan D

    2012-07-01

    Beaconing to rewarded locations is typically achieved by visual recognition of the actual goal. Spatial recognition, on the other hand, can occur in the absence of the goal itself, relying instead on the landmarks surrounding the goal location. Although the duration or frequency of experiences that an animal needs to learn the landmarks surrounding a goal have been extensively studied with a variety of laboratory tasks, little is known about the way in which wild vertebrates use them in their natural environment. Here, we allowed hummingbirds to feed once only from a rewarding flower (goal) before it was removed. When we presented a similar flower at a different height in another location, birds frequently returned to the location the flower had previously occupied (spatial recognition) before flying to the flower itself (beaconing). After experiencing three rewarded flowers, each in a different location, they were more likely to beacon to the current visible flower than they were to return to previously rewarded locations (without a visible flower). These data show that hummingbirds can encode a rewarded location on the basis of the surrounding landmarks after a single visit. After multiple goal location manipulations, however, the birds changed their strategy to beaconing presumably because they had learned that the flower itself reliably signalled reward.

  18. Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria: A meta-analysis and trial sequential analysis

    Science.gov (United States)

    Sun, Fengmei; Zhang, Juan; Pu, Yuepu

    2017-10-01

    This study is designed to perform a meta-analysis and trial sequential analysis (TSA) to investigate whether people with G6PD deficiency suffered less malarial infection. We searched from PubMed, Science Direct, Springer Link, CNKI, and Wan Fang databases for case-control study, cohort study or cross section study until April 2017. TSA was used to determine the state of evidence and calculate the required sample size. Eight case-control studies and five cross-sectional studies (30,683participants) were included in this meta-analysis. Compared with normal control group, we found significant protection from severe malaria (OR 0.644, 95% CI [0.493-0.842]; P=0.001) among people with decreasing G6PD activity. People with variations of G6PD gene at nucleotide 202(G6PD A-) were also found to be associated with resistance on severe malaria pooled (OR 0.851, 95% CI [0.779-0.930]; P =0.0001). Sex-stratified test suggested that protection of severe malaria is conferred to both G6PD A-males and heterozygous females (with a single copy of the variant). In conclusion, our study found a significant protection from severe malaria among G6PD deficient people compared to the

  19. Vitamin K2 supplementation and arterial stiffness among renal transplant recipients-a single-arm, single-center clinical trial.

    Science.gov (United States)

    Mansour, Anthony G; Hariri, Essa; Daaboul, Yazan; Korjian, Serge; El Alam, Andrew; Protogerou, Athanase D; Kilany, Hala; Karam, Albert; Stephan, Antoine; Bahous, Sola Aoun

    2017-09-01

    Subclinical vitamin K deficiency is prevalent among renal transplant recipients and is associated with an increased risk of cardiovascular disease. However, the association between vitamin K supplementation and improvement of arterial stiffness has not been explored in the renal transplant population. The KING trial (vitamin K2 In reNal Graft) is a single-arm study that evaluated the association between the change in vitamin K status and indices of arterial stiffness following 8 weeks of menaquinone-7 (vitamin K2) supplementation (360 μg once daily) among renal transplant recipients (n = 60). Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Subclinical vitamin K deficiency was defined as plasma concentration of dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP) >500 pmol/L.At baseline, 53.3% of the study subjects had subclinical vitamin K deficiency. Supplementation was associated with a 14.2% reduction in mean cfPWV at 8 weeks (cfPWV pre-vitamin K2 = 9.8 ± 2.2 m/s vs. cfPWV post-vitamin K2 = 8.4 ± 1.5 m/s; P K2 supplementation was associated with improvement in subclinical vitamin K deficiency and arterial stiffness. (Clinicaltrials.gov: NCT02517580). Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  20. Single-Staged Compared With Multi-Staged PCI in Multivessel NSTEMI Patients: The SMILE Trial.

    Science.gov (United States)

    Sardella, Gennaro; Lucisano, Luigi; Garbo, Roberto; Pennacchi, Mauro; Cavallo, Erika; Stio, Rocco Edoardo; Calcagno, Simone; Ugo, Fabrizio; Boccuzzi, Giacomo; Fedele, Francesco; Mancone, Massimo

    2016-01-26

    A lack of clarity exists about the role of complete coronary revascularization in patients presenting with non-ST-segment elevation myocardial infarction. The aim of our study was to compare long-term outcomes in terms of major adverse cardiovascular and cerebrovascular events of 2 different complete coronary revascularization strategies in patients with non-ST-segment elevation myocardial infarction and multivessel coronary artery disease: 1-stage percutaneous coronary intervention (1S-PCI) during the index procedure versus multistage percutaneous coronary intervention (MS-PCI) complete coronary revascularization during the index hospitalization. In the SMILE (Impact of Different Treatment in Multivessel Non ST Elevation Myocardial Infarction Patients: One Stage Versus Multistaged Percutaneous Coronary Intervention) trial, 584 patients were randomly assigned in a 1:1 manner to 1S-PCI or MS-PCI. The primary study endpoint was the incidence of major adverse cardiovascular and cerebrovascular events, which were defined as cardiac death, death, reinfarction, rehospitalization for unstable angina, repeat coronary revascularization (target vessel revascularization), and stroke at 1 year. The occurrence of the primary endpoint was significantly lower in the 1-stage group (1S-PCI: n = 36 [13.63%] vs. MS-PCI: n = 61 [23.19%]; hazard ratio [HR]: 0.549 [95% confidence interval (CI): 0.363 to 0.828]; p = 0.004). The 1-year rate of target vessel revascularization was significantly higher in the MS-PCI group (1S-PCI: n = 22 [8.33%] vs. MS-PCI: n = 40 [15.20%]; HR: 0.522 [95% CI: 0.310 to 0.878]; p = 0.01; p log-rank = 0.013). When the analyses were limited to cardiac death (1S-PCI: n = 9 [3.41%] vs. MS-PCI: n = 14 [5.32%]; HR: 0.624 [95% CI: 0.270 to 1.441]; p = 0.27) and myocardial infarction (1S-PCI: n = 7 [2.65%] vs. MS-PCI: n = 10 [3.80%]; HR: 0.678 [95% CI: 0.156 to 2.657]; p = 0.46), no significant differences were observed between groups. In multivessel

  1. Single-cell multiple gene expression analysis based on single-molecule-detection microarray assay for multi-DNA determination

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lu [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang, Xianwei [School of Life Sciences, Shandong University, Jinan 250100 (China); Zhang, Xiaoli [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China); Wang, Jinxing [School of Life Sciences, Shandong University, Jinan 250100 (China); Jin, Wenrui, E-mail: jwr@sdu.edu.cn [School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100 (China)

    2015-01-07

    Highlights: • A single-molecule-detection (SMD) microarray for 10 samples is fabricated. • The based-SMD microarray assay (SMA) can determine 8 DNAs for each sample. • The limit of detection of SMA is as low as 1.3 × 10{sup −16} mol L{sup −1}. • The SMA can be applied in single-cell multiple gene expression analysis. - Abstract: We report a novel ultra-sensitive and high-selective single-molecule-detection microarray assay (SMA) for multiple DNA determination. In the SMA, a capture DNA (DNAc) microarray consisting of 10 subarrays with 9 spots for each subarray is fabricated on a silanized glass coverslip as the substrate. On the subarrays, the spot-to-spot spacing is 500 μm and each spot has a diameter of ∼300 μm. The sequence of the DNAcs on the 9 spots of a subarray is different, to determine 8 types of target DNAs (DNAts). Thus, 8 types of DNAts are captured to their complementary DNAcs at 8 spots of a subarray, respectively, and then labeled with quantum dots (QDs) attached to 8 types of detection DNAs (DNAds) with different sequences. The ninth spot is used to detect the blank value. In order to determine the same 8 types of DNAts in 10 samples, the 10 DNAc-modified subarrays on the microarray are identical. Fluorescence single-molecule images of the QD-labeled DNAts on each spot of the subarray are acquired using a home-made single-molecule microarray reader. The amounts of the DNAts are quantified by counting the bright dots from the QDs. For a microarray, 8 types of DNAts in 10 samples can be quantified in parallel. The limit of detection of the SMA for DNA determination is as low as 1.3 × 10{sup −16} mol L{sup −1}. The SMA for multi-DNA determination can also be applied in single-cell multiple gene expression analysis through quantification of complementary DNAs (cDNAs) corresponding to multiple messenger RNAs (mRNAs) in single cells. To do so, total RNA in single cells is extracted and reversely transcribed into their cDNAs. Three

  2. Ibrutinib, lenalidomide, and rituximab in relapsed or refractory mantle cell lymphoma (PHILEMON): a multicentre, open-label, single-arm, phase 2 trial.

    Science.gov (United States)

    Jerkeman, Mats; Eskelund, Christian Winther; Hutchings, Martin; Räty, Riikka; Wader, Karin Fahl; Laurell, Anna; Toldbod, Helle; Pedersen, Lone Bredo; Niemann, Carsten Utoft; Dahl, Christina; Kuitunen, Hanne; Geisler, Christian H; Grønbæk, Kirsten; Kolstad, Arne

    2018-03-01

    Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients aged 18 years or older with relapsed or refractory mantle cell lymphoma who had previously been treated with at least one rituximab-containing regimen, an Eastern Cooperative Oncology Group performance status score of 0-3, and at least one site of measurable disease, and who met criteria for several laboratory-assessed parameters. Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only (cycle duration 56 days), given until disease progression or unacceptable toxicity. In the induction phase, patients received intravenous (375 mg/m 2 ) or subcutaneous (1400 mg) rituximab once a week during cycle 1 and then once every 8 weeks. Oral ibrutinib (560 mg once a day) was given to patients every day in the cycle, whereas oral lenalidomide (15 mg once a day) was given on days 1-21. The primary endpoint was overall response assessed in the intention-to-treat population according to Lugano criteria. Safety analysis included all patients who received the treatment, irrespective of eligibility or duration of treatment. The trial is ongoing, but is no longer accruing patients, and is registered with ClinicalTrials.gov, number NCT02460276. Between April 30, 2015, and June 1, 2016, we enrolled 50 patients with relapsed or refractory mantle cell lymphoma at ten centres in Sweden, Finland, Norway, and Denmark. At a median follow-up of 17·8 months (IQR 14·7-20·9), 38 (76%, 95% CI 63-86) patients had an overall response, including 28 (56%, 42-69) patients who had a complete response and ten (20%, 11-33) who had a

  3. Vinorelbine plus 3-weekly trastuzumab in metastatic breast cancer: a single-centre phase 2 trial

    Directory of Open Access Journals (Sweden)

    Staiano Maria

    2007-03-01

    Full Text Available Abstract Background After two studies reporting response rates higher than 70% in HER2-positive metastatic breast cancer with weekly trastuzumab and vinorelbine, we planned a phase 2 study to test activity of the same combination, with trastuzumab given every 3 weeks. Methods Patients with HER2-positive metastatic breast cancer (3+ at immunohistochemistry or positive at fluorescence in situ hybridization, PS ≤2, normal left-ventricular ejection fraction (LVEF and no more than one chemotherapy line for metastatic disease were eligible. Vinorelbine (30 mg/m2 was given on days 1&8 every 21 and trastuzumab (8 mg/kg day 1, then 6 mg/kg every 21 days. A single-stage phase 2 design, with p0 = 0.45, p1 = 0.65, type I and II error = 0.10, was applied; 22 objective responses were required in 39 patients. Results From Nov 2002 to May 2005, 50 patients were enrolled, with a median age of 54 years (range 31–81. Among 40 patients eligible for response assessment, there were 7 complete and 13 partial responses (overall response rate 50%; 95% exact CI 33.8–66.2; 11 patients had disease stabilization, lasting more than 6 months in 10 cases. Response rate did not vary according to patients and tumor characteristics, type and amount of previous chemotherapy. Within the whole series, median progression-free survival was 9.6 months (95% CI 7.3–12.3, median overall survival 22.7 months (95% CI 19.5-NA. Fifteen patients (30% developed brain metastases at a median time of 12 months (range 1–25. There was one toxic death due to renal failure in a patient receiving concomitant pamidronate. Twenty-three patients (46% had grade 3–4 neutropenia, 2 (4% grade 3 anemia, 4 (8% febrile neutropenia. Two patients stopped treatment because of grade 2 decline of LVEF and one patient because of grade 2 liver toxicity concomitant with a grade 1 decline of LVEF. One patient stopped trastuzumab after 50 cycles because of grade 1 decline of LVEF. Conclusion Although lower

  4. Increased intra-participant variability in children with autistic spectrum disorder: Evidence from single trial analyses of evoked EEG.

    Directory of Open Access Journals (Sweden)

    Elizabeth eMilne

    2011-03-01

    Full Text Available Intra-participant variability in clinical conditions such as autistic spectrum disorder (ASD is an important indicator of pathophysiological processing. The data reported here illustrate that trial-by-trial variability can be reliably measured from EEG, and that intra-participant EEG variability is significantly greater in those with ASD than in neuro-typical matched controls. EEG recorded at the scalp is a linear mixture of activity arising from muscle artifacts and numerous concurrent brain processes. To minimise these additional sources of variability, EEG data were subjected to two different methods of spatial filtering. (i The data were decomposed using infomax Independent Component Analysis (ICA, a method of blind source separation which un-mixes the EEG signal into components with maximally independent time-courses, and (ii a surface Laplacian transform was performed (Current Source Density interpolation in order to reduce the effects of volume conduction. Data are presented from thirteen high functioning adolescents with ASD without co-morbid ADHD, and twelve neuro-typical age- IQ- and gender-matched controls. Comparison of variability between the ASD and neuro-typical groups indicated that intra-participant variability of P1 latency and P1 amplitude was greater in the participants with ASD, and inter-trial α-band phase coherence was lower in the participants with ASD. These data support the suggestion that individuals with ASD are less able to synchronise the activity of stimulus-related cell assemblies than neuro-typical individuals, and provide empirical evidence in support of theories of increased neural noise in ASD.

  5. Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2010-01-01

    Full Text Available Mental Retardation (MR is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for “agitated” TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.

  6. Models for patients' recruitment in clinical trials and sensitivity analysis.

    Science.gov (United States)

    Mijoule, Guillaume; Savy, Stéphanie; Savy, Nicolas

    2012-07-20

    Taking a decision on the feasibility and estimating the duration of patients' recruitment in a clinical trial are very important but very hard questions to answer, mainly because of the huge variability of the system. The more elaborated works on this topic are those of Anisimov and co-authors, where they investigate modelling of the enrolment period by using Gamma-Poisson processes, which allows to develop statistical tools that can help the manager of the clinical trial to answer these questions and thus help him to plan the trial. The main idea is to consider an ongoing study at an intermediate time, denoted t(1). Data collected on [0,t(1)] allow to calibrate the parameters of the model, which are then used to make predictions on what will happen after t(1). This method allows us to estimate the probability of ending the trial on time and give possible corrective actions to the trial manager especially regarding how many centres have to be open to finish on time. In this paper, we investigate a Pareto-Poisson model, which we compare with the Gamma-Poisson one. We will discuss the accuracy of the estimation of the parameters and compare the models on a set of real case data. We make the comparison on various criteria : the expected recruitment duration, the quality of fitting to the data and its sensitivity to parameter errors. We discuss the influence of the centres opening dates on the estimation of the duration. This is a very important question to deal with in the setting of our data set. In fact, these dates are not known. For this discussion, we consider a uniformly distributed approach. Finally, we study the sensitivity of the expected duration of the trial with respect to the parameters of the model : we calculate to what extent an error on the estimation of the parameters generates an error in the prediction of the duration.

  7. Review of Recent Methodological Developments in Group-Randomized Trials: Part 2-Analysis.

    Science.gov (United States)

    Turner, Elizabeth L; Prague, Melanie; Gallis, John A; Li, Fan; Murray, David M

    2017-07-01

    In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.

  8. Bilinear common spatial pattern for single-trial ERP-based rapid serial visual presentation triage

    Science.gov (United States)

    Yu, K.; Shen, K.; Shao, S.; Ng, W. C.; Li, X.

    2012-08-01

    Common spatial pattern (CSP) analysis is a useful tool for the feature extraction of event-related potentials (ERP). However, CSP is essentially time invariant, and thus unable to exploit the temporal information of ERP. This paper proposes a variant of CSP, namely bilinear common spatial pattern (BCSP), which is capable of accommodating both spatial and temporal information. BCSP generalizes CSP through iteratively optimizing bilinear filters. These bilinear filters constitute a spatio-temporal subspace in which the separation between two conditions is maximized. The method is unique in the sense that it is mathematically intuitive and simple, as all the bilinear filters are obtained by maximizing the power ratio as CSP does. The proposed method was evaluated on 20 subjects’ ERP data collected in rapid serial visual presentation triage experiments. The results show that BCSP achieved significantly higher average test accuracy (12.3% higher, p < 0.001).

  9. Photobiomodulation by helium neon and diode lasers in an excisional wound model: A single blinded trial

    Directory of Open Access Journals (Sweden)

    Snehil Dixit

    2012-01-01

    Full Text Available Background: Application of different kinds of lasers in clinical and experimental studies causes photobiomodulation that works at localized cellular and humoral level on various biological systems. Increased numbers of fibroblasts, myofibroblast, and degranulation of mast cells have been the observed benefits post-irradiation. Objective: Was to find out the effect of irradiation with energy densities of 3.38 J/cm 2 , 8 J/cm 2 , and 18 J/cm 2 on animal tissue (albino wistar rats in an excisional wound model and to assess changes in biochemical (hydroxyproline and histopathological levels in excisional wound model. Materials and Methods: The animals were divided into 4 groups, which were labeled as L1, diode laser (18 J/cm 2 , L2 Helium-neon (He-Ne, 8 J/cm 2 , L3 diode laser (3.38 J/cm 2 , and sham treatment for control was depicted by C, respectively. Histological and hydroxyproline analysis was performed on 7, 14, 21 days of post-wounding. One-way analysis of variance, ANOVA and Bonferroni′s multiple comparison tests were done for tissue hydroxyproline levels. Results: There was no significant increase in the hydroxyproline content (P < 0.005 when observed in study group and compared to controls. Whereas significant epithelizations was seen in group treated with He-Ne laser of intensity of 8 J/cm 2 . Conclusion: The experimental observations suggest that low intensity helium-neon laser of 8 J/cm 2 intensity facilitated photo stimulation by tissue repair, but failed to show significant tissue hydroxyproline levels in excisional wound model.

  10. The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

    Science.gov (United States)

    Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

    2017-01-01

    In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials. PMID:28042342

  11. Process control analysis of IMRT QA: implications for clinical trials

    International Nuclear Information System (INIS)

    Pawlicki, Todd; Rice, Roger K; Yoo, Sua; Court, Laurence E; McMillan, Sharon K; Russell, J Donald; Pacyniak, John M; Woo, Milton K; Basran, Parminder S; Boyer, Arthur L; Bonilla, Claribel

    2008-01-01

    The purpose of this study is two-fold: first is to investigate the process of IMRT QA using control charts and second is to compare control chart limits to limits calculated using the standard deviation (σ). Head and neck and prostate IMRT QA cases from seven institutions in both academic and community settings are considered. The percent difference between the point dose measurement in phantom and the corresponding result from the treatment planning system (TPS) is used for analysis. The average of the percent difference calculations defines the accuracy of the process and is called the process target. This represents the degree to which the process meets the clinical goal of 0% difference between the measurements and TPS. IMRT QA process ability defines the ability of the process to meet clinical specifications (e.g. 5% difference between the measurement and TPS). The process ability is defined in two ways: (1) the half-width of the control chart limits, and (2) the half-width of ±3σ limits. Process performance is characterized as being in one of four possible states that describes the stability of the process and its ability to meet clinical specifications. For the head and neck cases, the average process target across institutions was 0.3% (range: -1.5% to 2.9%). The average process ability using control chart limits was 7.2% (range: 5.3% to 9.8%) compared to 6.7% (range: 5.3% to 8.2%) using standard deviation limits. For the prostate cases, the average process target across the institutions was 0.2% (range: -1.8% to 1.4%). The average process ability using control chart limits was 4.4% (range: 1.3% to 9.4%) compared to 5.3% (range: 2.3% to 9.8%) using standard deviation limits. Using the standard deviation to characterize IMRT QA process performance resulted in processes being preferentially placed in one of the four states. This is in contrast to using control charts for process characterization where the IMRT QA processes were spread over three of the

  12. The "when" and the "where" of single-trial allocentric spatial memory performance in young children: Insights into the development of episodic memory.

    Science.gov (United States)

    Ribordy Lambert, Farfalla; Lavenex, Pierre; Banta Lavenex, Pamela

    2017-03-01

    Allocentric spatial memory, "where" with respect to the surrounding environment, is one of the three fundamental components of episodic memory: what, where, when. Whereas basic allocentric spatial memory abilities are reliably observed in children after 2 years of age, coinciding with the offset of infantile amnesia, the resolution of allocentric spatial memory acquired over repeated trials improves from 2 to 4 years of age. Here, we first show that single-trial allocentric spatial memory performance improves in children from 3.5 to 7 years of age, during the typical period of childhood amnesia. Second, we show that large individual variation exists in children's performance at this age. Third, and most importantly, we show that improvements in single-trial allocentric spatial memory performance are due to an increasing ability to spatially and temporally separate locations and events. Such improvements in spatial and temporal processing abilities may contribute to the gradual offset of childhood amnesia. © 2016 Wiley Periodicals, Inc.

  13. Hypothermia after cardiac arrest should be further evaluated-A systematic review of randomised trials with meta-analysis and trial sequential analysis

    DEFF Research Database (Denmark)

    Nielsen, Niklas; Friberg, Hans; Gluud, Christian

    2011-01-01

    BACKGROUND: Guidelines recommend mild induced hypothermia (MIH) to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. Our objective was to systematically evaluate the evidence for MIH taking into consideration the risks of systematic and random error and to GRADE...... the evidence. METHODS: Systematic review with meta-analysis and trial sequential analysis of randomised trials evaluating MIH after cardiac arrest in adults. We searched CENTRAL, MEDLINE, and EMBASE databases until May 2009. Retrieved trials were evaluated with Cochrane methodology. Meta-analytic estimates....... The substantial risk of bias and concerns with directness rated down the quality of the evidence to low. CONCLUSIONS: Evidence regarding MIH after out-of-hospital cardiac arrest is still inconclusive and associated with non-negligible risks of systematic and random errors. Using GRADE-methodology, we conclude...

  14. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

    DEFF Research Database (Denmark)

    Krag, Mette; Perner, Anders; Wetterslev, Jørn

    2014-01-01

    PURPOSE: To assess the effects of stress ulcer prophylaxis (SUP) versus placebo or no prophylaxis on all-cause mortality, gastrointestinal (GI) bleeding and hospital-acquired pneumonia in adult critically ill patients in the intensive care unit (ICU). METHODS: We performed a systematic review using...... meta-analysis and trial sequential analysis (TSA). Eligible trials were randomised clinical trials comparing proton pump inhibitors or histamine 2 receptor antagonists with either placebo or no prophylaxis. Two reviewers independently assessed studies for inclusion and extracted data. The Cochrane...... of bias. There was no statistically significant difference in mortality (fixed effect: RR 1.00, 95% CI 0.84-1.20; P = 0.87; I(2) = 0%) or hospital-acquired pneumonia (random effects: RR 1.23, 95% CI 0.86-1.78; P = 0.28; I(2) = 19%) between SUP patients and the no prophylaxis/placebo patients...

  15. Thermal Hydraulic Analysis of K-DEMO Single Blanket Module for Preliminary Accident Analysis using MELCOR

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sung Bo; Bang, In Cheol [UNIST, Ulsan (Korea, Republic of)

    2016-05-15

    To develop the Korean fusion commercial reactor, preliminary design concept for K-DEMO (Korean fusion demonstration reactor) has been announced by NFRI (National Fusion Research Institute). This pre-conceptual study of K-DEMO has been introduced to identify technical details of a fusion power plant for the future commercialization of fusion reactor in Korea. Before this consideration, to build the K-DEMO, accident analysis is essential. Since the Fukushima accident, which is severe accident from unexpected disaster, safety analysis of nuclear power plant has become important. The safety analysis of both fission and fusion reactors is deemed crucial in demonstrating the low radiological effect of these reactors on the environment, during severe accidents. A risk analysis of K-DEMO should be performed, as a prerequisite for the construction of a fusion reactor. In this research, thermal-hydraulic analysis of single blanket module of K-DEMO is conducted for preliminary accident analysis for K-DEMO. Further study about effect of flow distributer is conducted. The normal K-DEMO operation condition is applied to the boundary condition and simulated to verify the material temperature limit using MELCOR. MELCOR is fully integrated, relatively fast-running code developed by Sandia National Laboratories. MELCOR had been used for Light Water Reactors and fusion reactor version of MELCOR was developed for ITER accident analysis. This study shows the result of thermal-hydraulic simulation of single blanket module with MELCOR which is severe accident code for nuclear fusion safety analysis. The difference of mass flow rate for each coolant channel with or without flow distributer is presented. With flow distributer, advantage of broadening temperature gradient in the K-DEMO blanket module and increase mass flow toward first wall is obtained. This can enhance the safety of K-DEMO blanket module. Most 13 .deg. C temperature difference in blanket module is obtained.

  16. Predictive factors for the placebo effect in clinical trials for dry eye: a pooled analysis of three clinical trials.

    Science.gov (United States)

    Imanaka, Takahiro; Sato, Izumi; Tanaka, Shiro; Kawakami, Koji

    2017-11-01

    Placebo effect is one of the methodological difficulties in dry eye clinical trials. If we could elucidate the tendencies of the placebo response and find predictors, we could reduce the placebo response in clinical trials for dry eye. In this study, we investigated the predictive factors for the placebo effect in dry eye clinical trials. A total of 205 patients with dry eye assigned to the placebo arms of three placebo-controlled randomised clinical trials were analysed by simple and multivariable regression analysis. The corneal fluorescein (FL) staining score and dry eye symptoms were studied at week 4. The variables of interest included gender, age, complications of Sjögren's syndrome, Schirmer's test I value, tear break-up time and conjunctival hyperaemia score. We also conducted a stratified analysis according to the patients' age. Among all the studied endpoints, the baseline scores were significantly related to the corresponding placebo response. In addition, for the FL score and the dryness score, age was a significant predictor of the placebo response (p=0.04 and p<0.0001, respectively). Stratified analysis by age showed that patients more than 40 years of age are more likely to have a stronger placebo response in the FL and dryness scores. The baseline scores and age were predictive factors of the placebo response in frequently used endpoints, such as FL score or dryness symptoms. These patient characteristics can be controlled by study design, and our findings enable the design of more efficient placebo-controlled studies with good statistical power. © 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.

  17. Single Trial Classification of Evoked EEG Signals Due to RGB Colors

    Directory of Open Access Journals (Sweden)

    Eman Alharbi

    2016-03-01

    Full Text Available Recently, the impact of colors on the brain signals has become one of the leading researches in BCI systems. These researches are based on studying the brain behavior after color stimulus, and finding a way to classify its signals offline without considering the real time. Moving to the next step, we present a real time classification model (online for EEG signals evoked by RGB colors stimuli, which is not presented in previous studies. In this research, EEG signals were recorded from 7 subjects through BCI2000 toolbox. The Empirical Mode Decomposition (EMD technique was used at the signal analysis stage. Various feature extraction methods were investigated to find the best and reliable set, including Event-related spectral perturbations (ERSP, Target mean with Feast Fourier Transform (FFT, Wavelet Packet Decomposition (WPD, Auto Regressive model (AR and EMD residual. A new feature selection method was created based on the peak's time of EEG signal when red and blue colors stimuli are presented. The ERP image was used to find out the peak's time, which was around 300 ms for the red color and around 450 ms for the blue color. The classification was performed using the Support Vector Machine (SVM classifier, LIBSVM toolbox being used for that purpose. The EMD residual was found to be the most reliable method that gives the highest classification accuracy with an average of 88.5% and with an execution time of only 14 seconds.

  18. Biomechanical analysis of the single-leg decline squat

    NARCIS (Netherlands)

    Zwerver, J.; Bredeweg, S. W.; Hof, A. L.

    Background: The single-leg squat on a 25 decline board has been described as a clinical assessment tool and as a rehabilitation exercise for patients with patellar tendinopathy. Several assumptions have been made about its working mechanism on patellar load and patellofemoral forces, but these are

  19. Simulation and analysis of single-ribosome translation

    International Nuclear Information System (INIS)

    Tinoco, Ignacio Jr; Wen, Jin-Der

    2009-01-01

    In the cell, proteins are synthesized by ribosomes in a multi-step process called translation. The ribosome translocates along the messenger RNA to read the codons that encode the amino acid sequence of a protein. Elongation factors, including EF-G and EF-Tu, are used to catalyze the process. Recently, we have shown that translation can be followed at the single-molecule level using optical tweezers; this technique allows us to study the kinetics of translation by measuring the lifetime the ribosome spends at each codon. Here, we analyze the data from single-molecule experiments and fit the data with simple kinetic models. We also simulate the translation kinetics based on a multi-step mechanism from ensemble kinetic measurements. The mean lifetimes from the simulation were consistent with our experimental single-molecule measurements. We found that the calculated lifetime distributions were fit in general by equations with up to five rate-determining steps. Two rate-determining steps were only obtained at low concentrations of elongation factors. These analyses can be used to design new single-molecule experiments to better understand the kinetics and mechanism of translation

  20. Single-cell Analysis of Lambda Immunity Regulation

    DEFF Research Database (Denmark)

    Bæk, Kristoffer Torbjørn; Svenningsen, Sine Lo; Eisen, Harvey

    2003-01-01

    We have examined expression of the ¿cI operon in single cells via a rexgfp substitution. Although average fluorescence agreed with expectations for expression of ¿-repressor, fluorescence fluctuated greatly from cell-to-cell. Fluctuations in repressor concentration are not predicted by previous m...

  1. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    Science.gov (United States)

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  2. Working memory load-dependent spatio-temporal activity of single-trial P3 response detected with an adaptive wavelet denoiser.

    Science.gov (United States)

    Zhang, Qiushi; Yang, Xueqian; Yao, Li; Zhao, Xiaojie

    2017-03-27

    Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Use of intravenous tranexamic acid in total knee arthroplasty: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    FU De-jie

    2013-04-01

    Full Text Available 【Abstract】 Objective: The effect of tranexamic acid (TA on patients receiving total knee arthroplasty (TKA has been reported in many small clinical trials. But single trials are not sufficient enough to clarify the effectiveness and safety of TA. So, we carried out a meta-analysis of randomized controlled trials to investigate the efficacy and safety of the intravenous use of TA in TKA. Methods: Literatures were retrieved in Cochrane Library, OVID, PubMed, EMBASE, CNKI and Wanfang Data. All the related literatures were checked by two independent investigators and only the high quality randomized con-trolled trials were enrolled. Relevant data were analyzed using RevMan 5.1 to compare the difference of blood loss, transfusion and complications between TA group and con-trol group. Results: There were 353 related literatures and only 22 randomized controlled trials met the inclusion criteria. The use of TA in TKA significantly reduced total blood loss by a mean of 435.41 ml (95% CI 300.62-570.21, P<0.01, post-operative blood loss by a mean of 406.69 ml (95% CI 333.16-480.22, P<0.01. TA also significantly lowered the transfu-sion rate (risk difference 0.30, 95% CI 0.21-0.39, P<0.01 and transfusion volume (mean difference 0.95 unit, 95% CI 0.53-1.37, P<0.01. The risks between TA group and control group in developing deep vein thrombosis and pulmonary embo-lism were not statistically significant. Conclusion: TA is beneficial for patients undergoing TKA, which can significantly reduce total blood loss, post-operative blood loss, transfusion rate, and transfusion volume. Meanwhile TA is recommended to reduce deep vein thrombosis and pulmonary embolism following TKA. Key words: Tranexamic acid; Arthroplasty; Knee; Blood loss, surgical; Meta-analysis

  4. Single particle and molecular assembly analysis of polyribosomes by single- and double-tilt cryo electron tomography

    Energy Technology Data Exchange (ETDEWEB)

    Myasnikov, Alexander G. [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Integrative Structural Biology, Centre National de la Recherche Scientifique (CNRS) UMR 7104/ Institut National de la Santé de la Recherche Médicale INSERM U964/ Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch (France); Afonina, Zhanna A. [Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region (Russian Federation); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Department of Integrative Structural Biology, Centre National de la Recherche Scientifique (CNRS) UMR 7104/ Institut National de la Santé de la Recherche Médicale INSERM U964/ Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch (France)

    2013-03-15

    Cryo electron tomography (cryo-ET) can provide cellular and molecular structural information on various biological samples. However, the detailed interpretation of tomograms reconstructed from single-tilt data tends to suffer from low signal-to-noise ratio and artefacts caused by some systematically missing angular views. While these can be overcome by sub-tomogram averaging, they remain limiting for the analysis of unique structures. Double-tilt ET can improve the tomogram quality by acquiring a second tilt series after an in-plane rotation, but its usage is not widespread yet because it is considered technically demanding and it is rarely used under cryo conditions. Here we show that double-tilt cryo-ET improves the quality of 3D reconstructions so significantly that even single particle analysis can be envisaged despite of the intrinsically low image contrast obtained from frozen-hydrated specimens. This is illustrated by the analysis of eukaryotic polyribosomes in which individual ribosomes were reconstructed using single-tilt, partial and full double-tilt geometries. The improved tomograms favour the faster convergence of iterative sub-tomogram averaging and allow a better 3D classification using multivariate statistical analysis. Our study of single particles and molecular assemblies within polysomes illustrates that the dual-axis approach is particularly useful for cryo applications of ET, both for unique objects and for structures that can be classified and averaged. - Highlights: ► Double-tilt cryo-ET improves 3D reconstructions thus making single particle analysis possible. ► Dual-axis cryo-ET data favour a faster convergence of iterative sub-tomogram averaging. ► Individual ribosomes were reconstructed from single-tilt, partial/ full double-tilt geometries. ► Double-tilt cryo-ET facilitates analysis of larger molecular assemblies such as in cell sections. ► Dual-axis cryo-ET is applicable to unique objects and to structures that can be

  5. Intersection tests for single marker QTL analysis can be more powerful than two marker QTL analysis

    Directory of Open Access Journals (Sweden)

    Doerge RW

    2003-06-01

    Full Text Available Abstract Background It has been reported in the quantitative trait locus (QTL literature that when testing for QTL location and effect, the statistical power supporting methodologies based on two markers and their estimated genetic map is higher than for the genetic map independent methodologies known as single marker analyses. Close examination of these reports reveals that the two marker approaches are more powerful than single marker analyses only in certain cases. Simulation studies are a commonly used tool to determine the behavior of test statistics under known conditions. We conducted a simulation study to assess the general behavior of an intersection test and a two marker test under a variety of conditions. The study was designed to reveal whether two marker tests are always more powerful than intersection tests, or whether there are cases when an intersection test may outperform the two marker approach. We present a reanalysis of a data set from a QTL study of ovariole number in Drosophila melanogaster. Results Our simulation study results show that there are situations where the single marker intersection test equals or outperforms the two marker test. The intersection test and the two marker test identify overlapping regions in the reanalysis of the Drosophila melanogaster data. The region identified is consistent with a regression based interval mapping analysis. Conclusion We find that the intersection test is appropriate for analysis of QTL data. This approach has the advantage of simplicity and for certain situations supplies equivalent or more powerful results than a comparable two marker test.

  6. Electronic prompts significantly increase response rates to postal questionnaires: a randomized trial within a randomized trial and meta-analysis.

    Science.gov (United States)

    Clark, Laura; Ronaldson, Sarah; Dyson, Lisa; Hewitt, Catherine; Torgerson, David; Adamson, Joy

    2015-12-01

    To assess the effectiveness of sending electronic prompts to randomized controlled trial participants to return study questionnaires. A "trial within a trial" embedded within a study determining the effectiveness of chronic obstructive pulmonary disease (DOC) screening on smoking cessation. Those participants taking part in DOC who provided a mobile phone number and/or an electronic mail address were randomized to either receive an electronic prompt or no electronic prompt to return a study questionnaire. The results were combined with two previous studies in a meta-analysis. A total of 437 participants were randomized: 226 to the electronic prompt group and 211 to the control group. A total of 285 (65.2%) participants returned the follow-up questionnaire: 157 (69.5%) in the electronic prompt group and 128 (60.7%) in the control group [difference 8.8%; 95% confidence interval (CI): -0.11%, 17.7%; P = 0.05]. The mean time to response was 23 days in the electronic prompt group and 33 days in the control group (hazard ratio = 1.27; 95% CI: 1.105, 1.47). The meta-analysis of all three studies showed an increase in response rate of 7.1% (95% CI: 0.8%, 13.3%). The use of electronic prompts increased response rates and reduces the time to response. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy: a randomised controlled trial (the SELF study).

    Science.gov (United States)

    Littlewood, Chris; Bateman, Marcus; Brown, Kim; Bury, Julie; Mawson, Sue; May, Stephen; Walters, Stephen J

    2016-07-01

    To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. Multi-centre pragmatic unblinded parallel group randomised controlled trial. UK National Health Service. Patients with a clinical diagnosis of rotator cuff tendinopathy. The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement. The control group received usual physiotherapy treatment. The primary outcome measure was the Shoulder Pain & Disability Index (SPADI) at three months. Secondary outcomes included the SPADI at six and twelve months. A total of 86 patients (self-managed loaded exercise n=42; usual physiotherapy n=44) were randomised. Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up, leaving 60 (n=27; n=33) patients for intention to treat analysis. For the primary outcome, the mean SPADI score at three months was 32.4 (SD 20.2) for the self-managed group, and 30.7 (SD 19.7) for the usual physiotherapy treatment group; mean difference adjusted for baseline score: 3.2 (95% Confidence interval -6.0 to +12.4 P = 0.49).By six and twelve months there remained no significant difference between the groups. This study does not provide sufficient evidence of superiority of one intervention over the other in the short-, mid- or long-term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment. © The Author(s) 2015.

  8. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

    DEFF Research Database (Denmark)

    Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

    2017-01-01

    AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p birth. CONCLUSION: A single high...

  9. Comparison of Single Visit Post Endodontic Pain Using Mtwo Rotary and Hand K-File Instruments: A Randomized Clinical Trial.

    Science.gov (United States)

    Kashefinejad, Mohamad; Harandi, Azade; Eram, Saeed; Bijani, Ali

    2016-01-01

    Pain is an unpleasant outcome of endodontic treatment that can be unbearable to patients. Instrumentation techniques may affect the frequency and intensity of post-endodontic pain. This study aimed to compare single visit post endodontic pain using Mtwo (NiTi) rotary and hand K-file instruments. In this randomized controlled trial, 60 teeth with symptomatic irreversible pulpitis in 53 patients were selected and randomly assigned into two groups of 30 teeth. In group A, the root canals were prepared with Mtwo (NiTi) rotary instruments. In group B, the root canals were prepared with hand K-file instruments. Pain assessment was implemented using visual analog scale (VAS) at four, eight, 12 and 24 hours after treatment. The acquired data were analyzed using chi-square, Mann-Whitney U and Student's t-test (Protary instruments experienced significantly less post-endodontic pain than those treated with hand instruments (Protary instruments in root canal preparation contributed to lower incidence of postoperative pain than hand K-files.

  10. Comparison of Single Visit Post Endodontic Pain Using Mtwo Rotary and Hand K-File Instruments: A Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mohamad Kashefinejad

    2016-08-01

    Full Text Available Objectives: Pain is an unpleasant outcome of endodontic treatment that can be unbearable to patients. Instrumentation techniques may affect the frequency and intensity of post-endodontic pain. This study aimed to compare single visit post endodontic pain using Mtwo (NiTi rotary and hand K-file instruments.Materials and Methods: In this randomized controlled trial, 60 teeth with symptomatic irreversible pulpitis in 53 patients were selected and randomly assigned into two groups of 30 teeth. In group A, the root canals were prepared with Mtwo (NiTi rotary instruments. In group B, the root canals were prepared with hand K-file instruments. Pain assessment was implemented using visual analog scale (VAS at four, eight, 12 and 24 hours after treatment. The acquired data were analyzed using chi-square, Mann-Whitney U and Student’s t-test (P<0.05.Results: Patients treated with rotary instruments experienced significantly less post-endodontic pain than those treated with hand instruments (P<0.001.Conclusion: The use of Mtwo (NiTi rotary instruments in root canal preparation contributed to lower incidence of postoperative pain than hand K-files.

  11. A single trial of transcutaneous electrical nerve stimulation (TENS) improves spasticity and balance in patients with chronic stroke.

    Science.gov (United States)

    Cho, Hwi-young; In, Tae Sung; Cho, Ki Hun; Song, Chang Ho

    2013-03-01

    Spasticity management is pivotal for achieving functional recovery of stroke patients. The purpose of this study was to investigate the effects of a single trial of transcutaneous electrical nerve stimulation (TENS) on spasticity and balance in chronic stroke patients. Forty-two chronic stroke patients were randomly allocated into the TENS (n = 22) or the placebo-TENS (n = 20) group. TENS stimulation was applied to the gastrocnemius for 60 min at 100 Hz, 200 µs with 2 to 3 times the sensory threshold (the minimal threshold in detecting electrical stimulation for subjects) after received physical therapy for 30 min. In the placebo-TENS group, electrodes were placed but no electrical stimulation was administered. For measuring spasticity, the resistance encountered during passive muscle stretching of ankle joint was assessed using the Modified Ashworth Scale, and the Hand held dynamometer was used to assess the resistive force caused by spasticity. Balance ability was measured using a force platform that measures postural sway generated by postural imbalance. The TENS group showed a significantly greater reduction in spasticity of the gastrocnemius, compared to the placebo-TENS group (p TENS resulted in greater balance ability improvements, especially during the eyes closed condition (p TENS provides an immediately effective means of reducing spasticity and of improving balance in chronic stroke patients. The present data may be useful to establish the standard parameters for TENS application in the clinical setting of stroke.

  12. Exercise training and weight loss, not always a happy marriage: single blind exercise trials in females with diverse BMI.

    Science.gov (United States)

    Jackson, Matthew; Fatahi, Fardin; Alabduljader, Kholoud; Jelleyman, Charlotte; Moore, Jonathan P; Kubis, Hans-Peter

    2018-04-01

    Individuals show high variability in body weight responses to exercise training. Expectations and motivation towards effects of exercise on body weight might influence eating behaviour and could conceal regulatory mechanisms. We conducted 2 single-blind exercise trials (4 weeks (study 1) and 8 weeks (study 2)) with concealed objectives and exclusion of individuals with weight loss intention. Circuit exercise training programs (3 times a week (45-90 min), intensity 50%-90% peak oxygen uptake for 4 and 8 weeks) were conducted. Thirty-four females finished the 4-week intervention and 36 females the 8-week intervention. Overweight/obese (OV/OB) and lean female participants' weight/body composition responses were assessed and fasting and postprandial appetite hormone levels (PYY, insulin, amylin, leptin, ghrelin) were measured before and after the intervention for understanding potential contribution to individuals' body weight response to exercise training (study 2). Exercise training in both studies did not lead to a significant reduction of weight/body mass index (BMI) in the participants' groups; however, lean participants gained muscle mass. Appetite hormones levels were significantly (p training did not lead to weight loss in female participants, while a considerable proportion of variance in body weight response to training could be explained by individuals' appetite hormone levels and BMI.

  13. Gap junctions and memory: an investigation using a single trial discrimination avoidance task for the neonate chick.

    Science.gov (United States)

    Verwey, L J; Edwards, T M

    2010-02-01

    Gap junctions are important to how the brain functions but are relatively under-investigated with respect to their contribution towards behaviour. In the present study a single trial discrimination avoidance task was used to investigate the effect of the gap junction inhibitor 18-alpha-glycyrrhetinic acid (alphaGA) on retention. Past studies within our research group have implied a potential role for gap junctions during the short-term memory (STM) stage which decays by 15 min post-training. A retention function study comparing 10 microM alphaGA and vehicle given immediately post-training demonstrated a significant main effect for drug with retention loss at all times of test (10-180 min post-training). Given that the most common gap junction in the brain is that forming the astrocytic network it is reasonable to conclude that alphaGA was acting upon these. To confirm this finding and interpretation two additional investigations were undertaken using endothelin-1 (ET-1) and ET-1+tolbutamide. Importantly, a retention function study using 10nM ET-1 replicated the retention loss observed for alphaGA. In order to confirm that ET-1 was acting on astrocytic gap junctions the amnestic action of ET-1 was effectively challenged with increasing concentrations of tolbutamide. The present findings suggest that astrocytic gap junctions are important for memory processing. Copyright 2009 Elsevier Inc. All rights reserved.

  14. Upper limb training using Wii Sports Resort for children with hemiplegic cerebral palsy: a randomized, single-blind trial.

    Science.gov (United States)

    Chiu, Hsiu-Ching; Ada, Louise; Lee, Hsin-Min

    2014-10-01

    To investigate whether Wii Sports Resort training is effective and if any benefits are maintained. Randomized, single-blind trial. Sixty-two hemiplegic children with cerebral palsy (6-13 years). Experimental group undertook six weeks of home-based Wii Sports Resort training plus usual therapy, while the control group received usual therapy. Outcomes were coordination, strength, hand function, and carers' perception of hand function, measured at baseline, six, and 12 weeks by a blinded assessor. There was a trend of mean difference (MD) for the experimental group to have more grip strength by six (MD 4.0 N, 95% confidence interval (CI) -0.8 to 8.8, p = 0.10) and 12 (MD 4.1 N, 95% CI -2.1 to 10.3, p = 0.19) weeks, and to have a higher quantity of hand function according to carers' perception by six (MD 4.5 N, 95% CI -0.7 to 9.7, p = 0.09) and strengthened by 12 (MD 6.4, 95% CI 0.6 to 12.3, p = 0.03) weeks than the control group. There was no difference between groups in coordination and hand function by six or 12 weeks. Wii training did not improve coordination, strength, or hand function. Beyond the intervention, carers perceived that the children used their hands more. © The Author(s) 2014.

  15. 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Trippa, Fabio; Casale, Michelina; Costantini, Sara; Lupattelli, Marco; Bellavita, Rita; Marafioti, Luigi; Pergolizzi, Stefano; Santacaterina, Anna; Mignogna, Marcello; Silvano, Giovanni; Fusco, Vincenzo

    2009-01-01

    Background and purpose: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. Materials and methods: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). Results: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p = 0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. Conclusions: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

  16. Raman analysis of gold on WSe2 single crystal film

    International Nuclear Information System (INIS)

    Mukherjee, Bablu; Sun Leong, Wei; Li, Yida; Thong, John T L; Gong, Hao; Sun, Linfeng; Xiang Shen, Ze; Simsek, Ergun

    2015-01-01

    Synthesis and characterization of high-quality single-crystal tungsten diselenide (WSe 2 ) films on a highly insulating substrate is presented. We demonstrate for the first time that the presence of gold (Au) nanoparticles in the basal plane of a WSe 2 film can enhance its Raman scattering intensity. The experimentally observed enhancement ratio in the Raman signal correlates well with the simulated electric field intensity using both three-dimensional electromagnetic software and theoretical calculation considering layered medium coupled-dipole approximation (LM-CDA). This work serves as a guideline for the use of Au nanoparticles on WSe 2 single-crystal thin films for surface enhanced Raman scattering (SERS) applications in the future. (paper)

  17. Single-sweep spectral analysis of contact heat evoked potentials

    DEFF Research Database (Denmark)

    Hansen, Tine M; Graversen, Carina; Frøkjaer, Jens B

    2015-01-01

    AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single-sweep ch......AIMS: The cortical response to nociceptive thermal stimuli recorded as contact heat evoked potentials (CHEPs) may be altered by morphine. However, previous studies have averaged CHEPs over multiple stimuli, which are confounded by jitter between sweeps. Thus, the aim was to assess single...... by 13% (P = 0.04) and 9% (P = 0.007), while the beta and gamma bands were increased by 10% (P = 0.006) and 24% (P = 0.04). CONCLUSION: The decreases in the delta and theta band are suggested to represent a decrease in the pain specific morphology of the CHEPs, which indicates a diminished pain response...

  18. Addressable droplet microarrays for single cell protein analysis.

    Science.gov (United States)

    Salehi-Reyhani, Ali; Burgin, Edward; Ces, Oscar; Willison, Keith R; Klug, David R

    2014-11-07

    Addressable droplet microarrays are potentially attractive as a way to achieve miniaturised, reduced volume, high sensitivity analyses without the need to fabricate microfluidic devices or small volume chambers. We report a practical method for producing oil-encapsulated addressable droplet microarrays which can be used for such analyses. To demonstrate their utility, we undertake a series of single cell analyses, to determine the variation in copy number of p53 proteins in cells of a human cancer cell line.

  19. Applications of heavy ion microprobe for single event effects analysis

    International Nuclear Information System (INIS)

    Reed, Robert A.; Vizkelethy, Gyorgy; Pellish, Jonathan A.; Sierawski, Brian; Warren, Kevin M.; Porter, Mark; Wilkinson, Jeff; Marshall, Paul W.; Niu, Guofu; Cressler, John D.; Schrimpf, Ronald D.; Tipton, Alan; Weller, Robert A.

    2007-01-01

    The motion of ionizing-radiation-induced rogue charge carriers in a semiconductor can create unwanted voltage and current conditions within a microelectronic circuit. If sufficient unwanted charge or current occurs on a sensitive node, a variety of single event effects (SEEs) can occur with consequences ranging from trivial to catastrophic. This paper describes the application of heavy ion microprobes to assist with calibration and validation of SEE modeling approaches

  20. Analysis of a single-atom dipole trap

    International Nuclear Information System (INIS)

    Weber, Markus; Volz, Juergen; Saucke, Karen; Kurtsiefer, Christian; Weinfurter, Harald

    2006-01-01

    We describe a simple experimental technique which allows us to store a single 87 Rb atom in an optical dipole trap. Due to light-induced two-body collisions during the loading stage of the trap the maximum number of captured atoms is locked to one. This collisional blockade effect is confirmed by the observation of photon antibunching in the detected fluorescence light. The spectral properties of single photons emitted by the atom were studied with a narrow-band scanning cavity. We find that the atomic fluorescence spectrum is dominated by the spectral width of the exciting laser light field. In addition we observe a spectral broadening of the atomic fluorescence light due to the Doppler effect. This allows us to determine the mean kinetic energy of the trapped atom corresponding to a temperature of 105 μK. This simple single-atom trap is the key element for the generation of atom-photon entanglement required for future applications in quantum communication and a first loophole-free test of Bell's inequality

  1. Combining dosimetry and toxicity: analysis of two UK phase III clinical trials

    International Nuclear Information System (INIS)

    Gulliford, Sarah L

    2014-01-01

    There are many advantages to performing a clinical trial when implementing a novel radiotherapy technique. The clinical trials framework enables the safety and efficacy of the 'experimental arm' to be tested and ensures practical support, rigorous quality control and data monitoring for participating centres. In addition to the clinical and follow-up data collected from patients within the trial, it is also possible to collect 3-D dosimetric information from the corresponding radiotherapy treatment plans. Analysing the combination of dosimetric, clinical and follow-up data enhances the understanding of the relationship between the dose delivered to both the target and normal tissue structures and reported outcomes and toxicity. Aspects of the collection, collation and analysis of data from two UK multicentre Phase III radiotherapy trials are presented here. MRC-RT01 dose-escalation prostate radiotherapy trial ISRCTN47772397 was one of the first UK multi-centre radiotherapy trials to collect 3-D dosimetric data. A number of different analysis methodologies were implemented to investigate the relationship between the dose distribution to the rectum and specific rectal toxicities. More recently data was collected from the PARSPORT trial (Parotid Sparing IMRT vs conventional head and neck radiotherapy) ISRCTN48243537. In addition to the planned analysis, dosimetric analysis was employed to investigate an unexpected finding that acute fatigue was more prevalent in the IMRT arm of the trial. It can be challenging to collect 3-D dosimetric information from multicentre radiotherapy trials. However, analysing the relationship between dosimetric and toxicity data provides invaluable information which can influence the next generation of radiotherapy techniques.

  2. The effect of instruction in analgesic use compared with neuromuscular exercise on knee-joint load in patients with knee osteoarthritis: a randomized, single-blind, controlled trial.

    Science.gov (United States)

    Holsgaard-Larsen, A; Clausen, B; Søndergaard, J; Christensen, R; Andriacchi, T P; Roos, E M

    2017-04-01

    To investigate the effect of a neuro-muscular exercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis (OA). We hypothesized that knee joint loading during walking would be reduced by NEMEX and potentially increased by PHARMA. Single-blind, randomized controlled trial (RCT) comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee OA were randomly allocated (1:1) to one of two 8-week treatments. Primary outcome was change in knee load during walking (Knee Index, a composite score from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes were frontal plane peak knee adduction moment (KAM), Knee Injury and Osteoarthritis Outcome Scores (KOOS) and functional performance tests. Ninety three participants (57% women, 58 ± 8 years with a body mass index [BMI] of 27 ± 4 kg/m 2 (mean ± standard deviation [SD])) were randomized to NEMEX group (n = 47) or PHARMA (n = 46); data from 44 (94%) and 41 (89%) participants respectively, were available at follow-up. 49% of the participants in NEMEX and only 7% in PHARMA demonstrated good compliance. We found no difference in the primary outcome as evaluated by the Knee Index -0.07 [-0.17; 0.04] Nm/%BW HT. Secondary outcomes largely supported this finding. We found no difference in the primary outcome; knee joint load change during walking from a NEMEX program vs information on the recommended use of analgesics and anti-inflammatory drugs. ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012). Ethical Committee: S-20110153. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  3. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

    Science.gov (United States)

    Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

    2017-12-05

    To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track

  4. Can a single session of motor imagery promote motor learning of locomotion in older adults? A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Nicholson VP

    2018-04-01

    Full Text Available Vaughan P Nicholson,1 Justin WL Keogh,2–4 Nancy L Low Choy1 1School of Physiotherapy, Australian Catholic University, Brisbane, QLD, Australia; 2Faculty of Health Sciences and Medicine, Bond University, Robina, QLD, Australia; 3Human Potential Centre, AUT University, Auckland, New Zealand; 4Cluster for Health Improvement, Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sunshine Coast, QLD, Australia Purpose: To investigate the influence of a single session of locomotor-based motor imagery training on motor learning and physical performance. Patients and methods: Thirty independent adults aged >65 years took part in the randomized controlled trial. The study was conducted within an exercise science laboratory. Participants were randomly divided into three groups following baseline locomotor testing: motor imagery training, physical training, and control groups. The motor imagery training group completed 20 imagined repetitions of a locomotor task, the physical training group completed 20 physical repetitions of a locomotor task, and the control group spent 25 minutes playing mentally stimulating games on an iPad. Imagined and physical performance times were measured for each training repetition. Gait speed (preferred and fast, timed-up-and-go, gait variability and the time to complete an obstacle course were completed before and after the single training session. Results: Motor learning occurred in both the motor imagery training and physical training groups. Motor imagery training led to refinements in motor planning resulting in imagined movements better matching the physically performed movement at the end of training. Motor imagery and physical training also promoted improvements in some locomotion outcomes as demonstrated by medium to large effect size improvements after training for fast gait speed and timed-up-and-go. There were no training effects on gait variability. Conclusion: A single session

  5. A P300-based Brain-Computer Interface with Stimuli on Moving Objects: Four-Session Single-Trial and Triple-Trial Tests with a Game-Like Task Design

    Science.gov (United States)

    Ganin, Ilya P.; Shishkin, Sergei L.; Kaplan, Alexander Y.

    2013-01-01

    Brain-computer interfaces (BCIs) are tools for controlling computers and other devices without using muscular activity, employing user-controlled variations in signals recorded from the user’s brain. One of the most efficient noninvasive BCIs is based on the P300 wave of the brain’s response to stimuli and is therefore referred to as the P300 BCI. Many modifications of this BCI have been proposed to further improve the BCI’s characteristics or to better adapt the BCI to various applications. However, in the original P300 BCI and in all of its modifications, the spatial positions of stimuli were fixed relative to each other, which can impose constraints on designing applications controlled by this BCI. We designed and tested a P300 BCI with stimuli presented on objects that were freely moving on a screen at a speed of 5.4°/s. Healthy participants practiced a game-like task with this BCI in either single-trial or triple-trial mode within four sessions. At each step, the participants were required to select one of nine moving objects. The mean online accuracy of BCI-based selection was 81% in the triple-trial mode and 65% in the single-trial mode. A relatively high P300 amplitude was observed in response to targets in most participants. Self-rated interest in the task was high and stable over the four sessions (the medians in the 1st/4th sessions were 79/84% and 76/71% in the groups practicing in the single-trial and triple-trial modes, respectively). We conclude that the movement of stimulus positions relative to each other may not prevent the efficient use of the P300 BCI by people controlling their gaze, e.g., in robotic devices and in video games. PMID:24302977

  6. Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

    Science.gov (United States)

    Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

    2016-01-01

    Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

  7. Thermomechanical Stresses Analysis of a Single Event Burnout Process

    Science.gov (United States)

    Tais, Carlos E.; Romero, Eduardo; Demarco, Gustavo L.

    2009-06-01

    This work analyzes the thermal and mechanical effects arising in a power Diffusion Metal Oxide Semiconductor (DMOS) during a Single Event Burnout (SEB) process. For studying these effects we propose a more detailed simulation structure than the previously used by other authors, solving the mathematical models by means of the Finite Element Method. We use a cylindrical heat generation region, with 5 W, 10 W, 50 W and 100 W for emulating the thermal phenomena occurring during SEB processes, avoiding the complexity of the mathematical treatment of the ion-semiconductor interaction.

  8. Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

    Science.gov (United States)

    Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

    2012-06-01

    Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

  9. A single-arm Phase II validation study of preventing oxaliplatin-induced hypersensitivity reactions by dexamethasone: the AVOID trial

    Directory of Open Access Journals (Sweden)

    Yoshida Y

    2015-11-01

    Full Text Available Yoichiro Yoshida,1 Keiji Hirata,2 Hiroshi Matsuoka,3 Shigeyoshi Iwamoto,4 Masahito Kotaka,5 Hideto Fujita,6 Naoya Aisu,1 Seiichiro Hoshino,1 Takeo Kosaka,6 Kotaro Maeda,3 Fumiaki Kiyomi,7 Yuichi Yamashita1 1Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan; 2Department of Surgery, Fukuoka Sanno Hospital, Fukuoka, Japan; 3Department of Surgery, Fujita Health University School of Medicine, Toyoake, Japan; 4Department of Surgery, Kansai Medical University Hirakata Hospital, Osaka, Japan; 5Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan; 6Department of Surgical Oncology, Kanazawa Medical University, Uchinada, Japan; 7Academia, Industry and Government Collaborative Research Institute of Translational Medicine for Life Innovation, Fukuoka University, Fukuoka, Japan Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%–20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions.Patients and methods: The AVOID trial was a prospective, multicenter, open-label, single-arm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of

  10. Efficiency of piezosurgery technique in miniscrew supported en-masse retraction: a single-centre, randomized controlled trial.

    Science.gov (United States)

    Tunçer, Nilüfer Irem; Arman-Özçirpici, Ayça; Oduncuoglu, Bahar Füsun; Göçmen, Jülide Sedef; Kantarci, Alpdogan

    2017-11-30

    Piezoelectric surgery is a newly introduced technique for rapid tooth movement. However, the efficiency of this technique has not been investigated on en-masse retraction cases yet. To investigate the efficiency of piezosurgery technique in accelerating miniscrew supported en-masse retraction and study the biological tissue response. In addition, to show if this technique induces a difference in dental, skeletal and soft tissue changes on lateral cephalograms, and in canine and molar rotations, besides intercanine and intermolar widths on dental casts. We conducted a randomized, single-centred, parallel-group, controlled trial, requiring upper right and left first premolar extractions on 30 patients above the minimum age of 14 years at the beginning of retraction. Piezosurgery-assisted versus conventional en-masse retraction anchored from miniscrews placed between second premolars and first molars, bilaterally. The main outcome was the en-masse retraction rate. Secondary outcomes were gingival crevicular fluid (GCF) volume and GCF content of receptor activator of nuclear factor κβ ligand (RANKL), changes regarding cephalometric and dental cast variables, and miniscrew success rates. Accomplished with opaque, sealed envelopes. Applicable for data assessment only. Commenced in February 2013 and ended in October 2014. Thirty-one patients were included in the study and divided into 2 groups of piezosurgery (n = 16) and control (n = 15). After 9.3 months of follow-up, no statistically significant difference was observed between groups for neither retraction rates (P = 0.958) nor GCF parameters (P > 0.05). Changes in lateral cephalometric and dental cast variables, and miniscrew success rates did not show significant differences either. Based on the results of this study, piezosurgery technique was found to be ineffective in accelerating en-masse retraction, and promoting a difference in the studied GCF parameters, skeletal and dental variables. The trial was not

  11. Conceptual analysis of single-feed heterogeneous distillation columns

    Directory of Open Access Journals (Sweden)

    Carlos Arturo Martinez Riascos

    2015-05-01

    Full Text Available Separation in heterogeneous distillation columns is attained by interaction of two liquid and one vapor phases, interaction of three phases involves complexities due to the determination of vapor-liquid-liquid equilibrium and hence, in the design of separation units. Nevertheless, the liquid-liquid equilibrium allows developing separations that may be unfeasible by vapor-liquid equilibrium. In this way, heterogeneous azeotropic distillation is a useful operation for the separation of azeotropic and close-boiling mixtures. In this work, a new methodology for evaluating the feasibility of this process is developed. This methodology is an extension of that proposed by Castillo et al. (1998 for homogeneous systems. Operation leaves for heterogeneous systems are calculated using the concept of pinch point curves in order to establish the process feasibility. Heterogeneous columns with external decanter are considered as the only heterogeneous stage (OHED: only heterogeneous external decanter. The initialization process for the column calculation requires the selection of the distillate composition using thermodynamic criteria in order to guarantee homogeneous phases within the column. A system with industrial and academic relevance was considered as case study: water-acetic acid-amyl acetate. Results show that the developed shortcut method allows evaluating process feasibility and estimating design parameters, without the use of trial and error procedures implemented, with the aid of simulation tools.

  12. Use of an online portal to facilitate clinical trial recruitment: a preliminary analysis of Fox Trial Finder.

    Science.gov (United States)

    Rocker, Charlotte; Cappelletti, Lily; Marshall, Claudia; Meunier, Claire C; Brooks, Deborah W; Sherer, Todd; Chowdhury, Sohini

    2015-01-01

    As in other therapeutic areas, clinical studies in Parkinson's disease (PD) face significant recruitment challenges. However, qualitative surveys suggest that individuals with PD are willing to participate in clinical research. The Michael J. Fox Foundation therefore established Fox Trial Finder in 2011 to facilitate connection between PD research teams and volunteers. Characterize the research volunteers (with and without PD) registered on Fox Trial Finder as of June 2014, and the published, recruiting studies to identify trends and highlight gaps between research requirements and available volunteers. Profiles of volunteers with and without PD were analyzed to explore trends in geography, demographics, family history and, for those volunteers with PD, disease progression and treatment history. Clinical study profiles were analyzed to determine study type, phase, sponsor, focus, location and eligibility criteria. The analysis focused on volunteers and studies based in the United States. The database contained 26,261 US-based volunteers, including 19,243 volunteers (73%) with PD and 7,018 (27%) controls without PD. The average time since diagnosis for PD volunteers was 5.7 years and the average age at diagnosis was 58 years. Control volunteers were more likely than volunteers with PD to be female (67% vs. 35%) and to have a family history of PD (49% vs. 12%). Fox Trial Finder's registration history to date demonstrates the high level of willingness among individuals affected by PD to participate in clinical research and provide a significant amount of personal health information to facilitate that participation.

  13. Chip based single cell analysis for nanotoxicity assessment.

    Science.gov (United States)

    Shah, Pratikkumar; Kaushik, Ajeet; Zhu, Xuena; Zhang, Chengxiao; Li, Chen-Zhong

    2014-05-07

    Nanomaterials, because of their tunable properties and performances, have been utilized extensively in everyday life related consumable products and technology. On exposure, beyond the physiological range, nanomaterials cause health risks via affecting the function of organisms, genomic systems, and even the central nervous system. Thus, new analytical approaches for nanotoxicity assessment to verify the feasibility of nanomaterials for future use are in demand. The conventional analytical techniques, such as spectrophotometric assay-based techniques, usually require a lengthy and time-consuming process and often produce false positives, and often cannot be implemented at a single cell level measurement for studying cell behavior without interference from its surrounding environment. Hence, there is a demand for a precise, accurate, sensitive assessment for toxicity using single cells. Recently, due to the advantages of automation of fluids and minimization of human errors, the integration of a cell-on-a-chip (CoC) with a microfluidic system is in practice for nanotoxicity assessments. This review explains nanotoxicity and its assessment approaches with advantages/limitations and new approaches to overcome the confines of traditional techniques. Recent advances in nanotoxicity assessment using a CoC integrated with a microfluidic system are also discussed in this review, which may be of use for nanotoxicity assessment and diagnostics.

  14. Tools for Genomic and Transcriptomic Analysis of Microbes at Single-Cell Level

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    Zixi Chen

    2017-09-01

    Full Text Available Microbiologists traditionally study population rather than individual cells, as it is generally assumed that the status of individual cells will be similar to that observed in the population. However, the recent studies have shown that the individual behavior of each single cell could be quite different from that of the whole population, suggesting the importance of extending traditional microbiology studies to single-cell level. With recent technological advances, such as flow cytometry, next-generation sequencing (NGS, and microspectroscopy, single-cell microbiology has greatly enhanced the understanding of individuality and heterogeneity of microbes in many biological systems. Notably, the application of multiple ‘omics’ in single-cell analysis has shed light on how individual cells perceive, respond, and adapt to the environment, how heterogeneity arises under external stress and finally determines the fate of the whole population, and how microbes survive under natural conditions. As single-cell analysis involves no axenic cultivation of target microorganism, it has also been demonstrated as a valuable tool for dissecting the microbial ‘dark matter.’ In this review, current state-of-the-art tools and methods for genomic and transcriptomic analysis of microbes at single-cell level were critically summarized, including single-cell isolation methods and experimental strategies of single-cell analysis with NGS. In addition, perspectives on the future trends of technology development in the field of single-cell analysis was also presented.

  15. Challenges from variation across regions in cost effectiveness analysis in multi-regional clinical trials

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    Yunbo Chu

    2016-10-01

    Full Text Available Economic evaluation in the form of cost-effectiveness analysis has become a popular means to inform decisions in healthcare. With multi-regional clinical trials in a global development program becoming a new venue for drug efficacy testing in recent decades, questions in methods for cost-effectiveness analysis in the multi-regional clinical trials setting also emerge. This paper addresses some challenges from variation across regions in cost effectiveness analysis in multi-regional clinical trials. Several discussion points are raised for further attention and a multi-regional clinical trial example is presented to illustrate the implications in industrial application. A general message is delivered to call for a depth discussion by all stakeholders to reach an agreement on a good practice in cost-effectiveness analysis in the multi-regional clinical trials. Meanwhile, we recommend an additional consideration of cost-effectiveness analysis results based on the clinical evidence from a certain homogeneous population as sensitivity or scenario analysis upon data availability.

  16. Integrative treatment for low back pain: An exploratory systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Hu, Xiao-Yang; Chen, Ni-Ni; Chai, Qian-Yun; Yang, Guo-Yan; Trevelyan, Esmé; Lorenc, Ava; Liu, Jian-Ping; Robinson, Nicola

    2015-10-26

    Low back pain (LBP) is a common musculoskeletal condition often treated using integrative medicine (IM). Most reviews have focused on a single complementary and alternative medicine (CAM) therapy for LBP rather than evaluating wider integrative approaches. This exploratory systematic review aimed to identify randomized controlled trials (RCTs) and provide evidence on the effectiveness, cost effectiveness and adverse effects of integrative treatment for LBP. A literature search was conducted in 12 English and Chinese databases. RCTs evaluating an integrative treatment for musculoskeletal related LBP were included. Reporting, methodological quality and relevant clinical characteristics were assessed and appraised. Metaanalyses were performed for outcomes where trials were sufficiently homogenous. Fifty-six RCTs were identified evaluating integrative treatment for LBP. Although reporting and methodological qualities were poor, meta-analysis showed a favourable effect for integrative treatment over conventional and CAM treatment for back pain and function at 3 months or less follow-up. Two trials investigated costs, reporting £ 5332 per quality adjusted life years with 6 Alexander technique lessons plus exercise at 12 months follow-up; and an increased total costs of $244 when giving an additional up to 15 sessions of CAM package of care at 12 weeks. Sixteen trials mentioned safety; no severe adverse effects were reported. Integrative treatment that combines CAM with conventional therapies appeared to have beneficial effects on pain and function. However, evidence is limited due to heterogeneity, the relatively small numbers available for subgroup analyses and the low methodological quality of the included trials. Identification of studies of true IM was not possible due to lack of reporting of the intervention details (registration No. CRD42013003916).

  17. Spatial and environmental connectivity analysis in a cholera vaccine trial.

    Science.gov (United States)

    Emch, Michael; Ali, Mohammad; Root, Elisabeth D; Yunus, Mohammad

    2009-02-01

    This paper develops theory and methods for vaccine trials that utilize spatial and environmental information. Satellite imagery is used to identify whether households are connected to one another via water bodies in a study area in rural Bangladesh. Then relationships between neighborhood-level cholera vaccine coverage and placebo incidence and neighborhood-level spatial variables are measured. The study hypothesis is that unvaccinated people who are environmentally connected to people who have been vaccinated will be at lower risk compared to unvaccinated people who are environmentally connected to people who have not been vaccinated. We use four datasets including: a cholera vaccine trial database, a longitudinal demographic database of the rural population from which the vaccine trial participants were selected, a household-level geographic information system (GIS) database of the same study area, and high resolution Quickbird satellite imagery. An environmental connectivity metric was constructed by integrating the satellite imagery with the vaccine and demographic databases linked with GIS. The results show that there is a relationship between neighborhood rates of cholera vaccination and placebo incidence. Thus, people are indirectly protected when more people in their environmentally connected neighborhood are vaccinated. This result is similar to our previous work that used a simpler Euclidean distance neighborhood to measure neighborhood vaccine coverage [Ali, M., Emch, M., von Seidlein, L., Yunus, M., Sack, D. A., Holmgren, J., et al. (2005). Herd immunity conferred by killed oral cholera vaccines in Bangladesh. Lancet, 366(9479), 44-49]. Our new method of measuring environmental connectivity is more precise since it takes into account the transmission mode of cholera and therefore this study validates our assertion that the oral cholera vaccine provides indirect protection in addition to direct protection.

  18. Veterinary homeopathy: meta-analysis of randomised placebo-controlled trials.

    Science.gov (United States)

    Mathie, Robert T; Clausen, Jürgen

    2015-01-01

    Meta-analysis of randomised controlled trials (RCTs) of veterinary homeopathy has not previously been undertaken. For all medical conditions and species collectively, we tested the hypothesis that the outcome of homeopathic intervention (treatment and/or prophylaxis, individualised and/or non-individualised) is distinguishable from corresponding intervention using placebos. All facets of the review, including literature search strategy, study eligibility, data extraction and assessment of risk of bias, were described in an earlier paper. A trial was judged to comprise reliable evidence if its risk of bias was low or was unclear in specific domains of assessment. Effect size was reported as odds ratio (OR). A trial was judged free of vested interest if it was not funded by a homeopathic pharmacy. Meta-analysis was conducted using the random-effects model, with hypothesis-driven sensitivity analysis based on risk of bias. Nine of 15 trials with extractable data displayed high risk of bias; low or unclear risk of bias was attributed to each of the remaining six trials, only two of which comprised reliable evidence without overt vested interest. For all N = 15 trials, pooled OR = 1.69 [95% confidence interval (CI), 1.12 to 2.56]; P = 0.01. For the N = 2 trials with suitably reliable evidence, pooled OR = 2.62 [95% CI, 1.13 to 6.05]; P = 0.02). Meta-analysis provides some very limited evidence that clinical intervention in animals using homeopathic medicines is distinguishable from corresponding intervention using placebos. The low number and quality of the trials hinders a more decisive conclusion. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  19. Single-case research design in pediatric psychology: considerations regarding data analysis.

    Science.gov (United States)

    Cohen, Lindsey L; Feinstein, Amanda; Masuda, Akihiko; Vowles, Kevin E

    2014-03-01

    Single-case research allows for an examination of behavior and can demonstrate the functional relation between intervention and outcome in pediatric psychology. This review highlights key assumptions, methodological and design considerations, and options for data analysis. Single-case methodology and guidelines are reviewed with an in-depth focus on visual and statistical analyses. Guidelines allow for the careful evaluation of design quality and visual analysis. A number of statistical techniques have been introduced to supplement visual analysis, but to date, there is no consensus on their recommended use in single-case research design. Single-case methodology is invaluable for advancing pediatric psychology science and practice, and guidelines have been introduced to enhance the consistency, validity, and reliability of these studies. Experts generally agree that visual inspection is the optimal method of analysis in single-case design; however, statistical approaches are becoming increasingly evaluated and used to augment data interpretation.

  20. Gastric Lavage in Acute Organophosphorus Pesticide poisoning (GLAOP – a randomised controlled trial of multiple vs. single gastric lavage in unselected acute organophosphorus pesticide poisoning

    Directory of Open Access Journals (Sweden)

    Cao YuPing

    2006-10-01

    Full Text Available Abstract Background Organophosphorus (OP pesticide poisoning is the most common form of pesticide poisoning in many Asian countries. Guidelines in western countries for management of poisoning indicate that gastric lavage should be performed only if two criteria are met: within one hour of poison ingestion and substantial ingested amount. But the evidence on which these guidelines are based is from medicine overdoses in developed countries and may be irrelevant to OP poisoning in Asia. Chinese clinical experience suggests that OP remains in the stomach for several hours or even days after ingestion. Thus, there may be reasons for doing single or multiple gastric lavages for OP poisoning. There have been no randomised controlled trials (RCTs to assess this practice of multiple lavages. Since it is currently standard therapy in China, we cannot perform a RCT of no lavage vs. a single lavage vs. multiple lavages. We will compare a single gastric lavage with three gastric lavages as the first stage to assess the role of gastric lavage in OP poisoning. Methods/Design We have designed an RCT assessing the effectiveness of multiple gastric lavages in adult OP self-poisoning patients admitted to three Chinese hospitals within 12 hrs of ingestion. Patients will be randomised to standard treatment plus either a single gastric lavage on admission or three gastric lavages at four hour intervals. The primary outcome is in-hospital mortality. Analysis will be on an intention-to-treat basis. On the basis of the historical incidence of OP at the study sites, we expect to enroll 908 patients over three years. This projected sample size provides sufficient power to evaluate the death rate; and a variety of other exposure and outcome variables, including particular OPs and ingestion time. Changes of OP level will be analyzed in order to provide some toxic kinetic data. Discussion the GLAOP study is a novel, prospective cohort study that will explore to the toxic

  1. Do soft skills predict surgical performance?: a single-center randomized controlled trial evaluating predictors of skill acquisition in virtual reality laparoscopy.

    Science.gov (United States)

    Maschuw, K; Schlosser, K; Kupietz, E; Slater, E P; Weyers, P; Hassan, I

    2011-03-01

    Virtual reality (VR) training in minimal invasive surgery (MIS) is feasible in surgical residency and beneficial for the performance of MIS by surgical trainees. Research on stress-coping of surgical trainees indicates the additional impact of soft skills on VR performance in the surgical curriculum. The aim of this study was to evaluate the impact of structured VR training and soft skills on VR performance of trainees. The study was designed as a single-center randomized controlled trial. Fifty first-year surgical residents with limited experience in MIS ("camera navigation" in laparoscopic cholecystectomy only) were randomized for either 3 months of VR training or no training. Basic VR performance and defined soft skills (self-efficacy, stress-coping, and motivation) were assessed prior to randomization using basic modules of the VR simulator LapSim(®) and standardized psychological questionnaires. Three months after randomization VR performance was reassessed. Outcome measurement was based on the results derived from the most complex of the basic VR modules ("diathermy cutting") as the primary end point. A correlation analysis of the VR end-point performance and the psychological scores was done in both groups. Structured VR training enhanced VR performance of surgical trainees. An additional correlation to high motivational states (P 0.05). Low self-efficacy and negative stress-coping strategies seem to predict poor VR performance. However, structured training along with high motivational states is likely to balance out this impairment.

  2. Classification using diffraction patterns for single-particle analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Hongli; Zhang, Kaiming [Department of Biophysics, the Health Science Centre, Peking University, Beijing 100191 (China); Meng, Xing, E-mail: xmeng101@gmail.com [Wadsworth Centre, New York State Department of Health, Albany, New York 12201 (United States)

    2016-05-15

    An alternative method has been assessed; diffraction patterns derived from the single particle data set were used to perform the first round of classification in creating the initial averages for proteins data with symmetrical morphology. The test protein set was a collection of Caenorhabditis elegans small heat shock protein 17 obtained by Cryo EM, which has a tetrahedral (12-fold) symmetry. It is demonstrated that the initial classification on diffraction patterns is workable as well as the real-space classification that is based on the phase contrast. The test results show that the information from diffraction patterns has the enough details to make the initial model faithful. The potential advantage using the alternative method is twofold, the ability to handle the sets with poor signal/noise or/and that break the symmetry properties. - Highlights: • New classification method. • Create the accurate initial model. • Better in handling noisy data.

  3. Classification using diffraction patterns for single-particle analysis

    International Nuclear Information System (INIS)

    Hu, Hongli; Zhang, Kaiming; Meng, Xing

    2016-01-01

    An alternative method has been assessed; diffraction patterns derived from the single particle data set were used to perform the first round of classification in creating the initial averages for proteins data with symmetrical morphology. The test protein set was a collection of Caenorhabditis elegans small heat shock protein 17 obtained by Cryo EM, which has a tetrahedral (12-fold) symmetry. It is demonstrated that the initial classification on diffraction patterns is workable as well as the real-space classification that is based on the phase contrast. The test results show that the information from diffraction patterns has the enough details to make the initial model faithful. The potential advantage using the alternative method is twofold, the ability to handle the sets with poor signal/noise or/and that break the symmetry properties. - Highlights: • New classification method. • Create the accurate initial model. • Better in handling noisy data.

  4. Condensing Raman spectrum for single-cell phenotype analysis

    KAUST Repository

    Sun, Shiwei; Wang, Xuetao; Gao, Xin; Ren, Lihui; Su, Xiaoquan; Bu, Dongbo; Ning, Kang

    2015-01-01

    In this work, we have proposed an approach called rDisc to discretize the original Raman spectrum into only a few (usually less than 20) representative peaks (Raman shifts). The approach has advantages in removing noises, and condensing the original spectrum. In particular, effective signal processing procedures were designed to eliminate noise, utilising wavelet transform denoising, baseline correction, and signal normalization. In the discretizing process, representative peaks were selected to signicantly decrease the Raman data size. More importantly, the selected peaks are chosen as suitable to serve as key biological markers to differentiate species and other cellular features. Additionally, the classication performance of discretized spectra was found to be comparable to full spectrum having more than 1000 Raman shifts. Overall, the discretized spectrum needs about 5storage space of a full spectrum and the processing speed is considerably faster. This makes rDisc clearly superior to other methods for single-cell classication.

  5. Directions for new developments on statistical design and analysis of small population group trials.

    Science.gov (United States)

    Hilgers, Ralf-Dieter; Roes, Kit; Stallard, Nigel

    2016-06-14

    Most statistical design and analysis methods for clinical trials have been developed and evaluated where at least several hundreds of patients could be recruited. These methods may not be suitable to evaluate therapies if the sample size is unavoidably small, which is usually termed by small populations. The specific sample size cut off, where the standard methods fail, needs to be investigated. In this paper, the authors present their view on new developments for design and analysis of clinical trials in small population groups, where conventional statistical methods may be inappropriate, e.g., because of lack of power or poor adherence to asymptotic approximations due to sample size restrictions. Following the EMA/CHMP guideline on clinical trials in small populations, we consider directions for new developments in the area of statistical methodology for design and analysis of small population clinical trials. We relate the findings to the research activities of three projects, Asterix, IDeAl, and InSPiRe, which have received funding since 2013 within the FP7-HEALTH-2013-INNOVATION-1 framework of the EU. As not all aspects of the wide research area of small population clinical trials can be addressed, we focus on areas where we feel advances are needed and feasible. The general framework of the EMA/CHMP guideline on small population clinical trials stimulates a number of research areas. These serve as the basis for the three projects, Asterix, IDeAl, and InSPiRe, which use various approaches to develop new statistical methodology for design and analysis of small population clinical trials. Small population clinical trials refer to trials with a limited number of patients. Small populations may result form rare diseases or specific subtypes of more common diseases. New statistical methodology needs to be tailored to these specific situations. The main results from the three projects will constitute a useful toolbox for improved design and analysis of small

  6. The effect of a single infusion of zoledronic acid on early implant migration in total hip arthroplasty. A randomized, double-blind, controlled trial.

    Science.gov (United States)

    Friedl, Gerald; Radl, Roman; Stihsen, Christoph; Rehak, Peter; Aigner, Reingard; Windhager, Reinhard

    2009-02-01

    Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.

  7. Average effect estimates remain similar as evidence evolves from single trials to high-quality bodies of evidence: a meta-epidemiologic study.

    Science.gov (United States)

    Gartlehner, Gerald; Dobrescu, Andreea; Evans, Tammeka Swinson; Thaler, Kylie; Nussbaumer, Barbara; Sommer, Isolde; Lohr, Kathleen N

    2016-01-01

    The objective of our study was to use a diverse sample of medical interventions to assess empirically whether first trials rendered substantially different treatment effect estimates than reliable, high-quality bodies of evidence. We used a meta-epidemiologic study design using 100 randomly selected bodies of evidence from Cochrane reports that had been graded as high quality of evidence. To determine the concordance of effect estimates between first and subsequent trials, we applied both quantitative and qualitative approaches. For quantitative assessment, we used Lin's concordance correlation and calculated z-scores; to determine the magnitude of differences of treatment effects, we calculated standardized mean differences (SMDs) and ratios of relative risks. We determined qualitative concordance based on a two-tiered approach incorporating changes in statistical significance and magnitude of effect. First trials both overestimated and underestimated the true treatment effects in no discernible pattern. Nevertheless, depending on the definition of concordance, effect estimates of first trials were concordant with pooled subsequent studies in at least 33% but up to 50% of comparisons. The pooled magnitude of change as bodies of evidence advanced from single trials to high-quality bodies of evidence was 0.16 SMD [95% confidence interval (CI): 0.12, 0.21]. In 80% of comparisons, the difference in effect estimates was smaller than 0.5 SMDs. In first trials with large treatment effects (>0.5 SMD), however, estimates of effect substantially changed as new evidence accrued (mean change 0.68 SMD; 95% CI: 0.50, 0.86). Results of first trials often change, but the magnitude of change, on average, is small. Exceptions are first trials that present large treatment effects, which often dissipate as new evidence accrues. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effect of tomato consumption on high-density lipoprotein cholesterol level: a randomized, single-blinded, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Cuevas-Ramos D

    2013-07-01

    Full Text Available Daniel Cuevas-Ramos,1 Paloma Almeda-Valdés,1 Emma Chávez-Manzanera,1 Clara Elena Meza-Arana,2 Griselda Brito-Córdova,1 Roopa Mehta,1 Oscar Pérez-Méndez,3 Francisco J Gómez-Pérez1 1Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 3Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico Introduction: Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C. This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels. Subject and methods: We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men 40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P > 0.0001. Conclusion: Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women. Keywords: lycopene, hypoalphalipoproteinemia, dyslipidemia, overweight, cardiovascular diseases

  9. Tinnitus Suppression by Intracochlear Electrical Stimulation in Single Sided Deafness - A Prospective Clinical Trial: Follow-Up.

    Directory of Open Access Journals (Sweden)

    Remo A G J Arts

    Full Text Available Earlier studies show that a Cochlear Implant (CI, capable of providing intracochlear electrical stimulation independent of environmental sounds, appears to suppress tinnitus at least for minutes. The current main objective is to compare the long-term suppressive effects of looped (i.e. repeated electrical stimulation (without environmental sound perception with the standard stimulation pattern of a CI (with environmental sound perception. This could open new possibilities for the development of a "Tinnitus Implant" (TI, an intracochlear pulse generator for the suppression of tinnitus.Ten patients with single sided deafness suffering from unilateral tinnitus in the deaf ear are fitted with a CI (MED-EL Corporation, Innsbruck, Austria. Stimulation patterns are optimized for each individual patient, after which they are compared using a randomized crossover design, with a follow-up of six months, followed by a 3 month period using the modality of patient's choice.Results show that tinnitus can be suppressed with intracochlear electrical stimulation independent of environmental sounds, even long term. No significant difference in tinnitus suppression was found between the standard clinical CI and the TI.It can be concluded that coding of environmental sounds is no requirement for tinnitus suppression with intracochlear electrical stimulation. It is therefore plausible that tinnitus suppression by CI is not solely caused by an attention shift from the tinnitus to environmental sounds. Both the standard clinical CI and the experimental TI are potential treatment options for tinnitus. These findings offer perspectives for a successful clinical application of the TI, possibly even in patients with significant residual hearing.TrialRegister.nl NTR3374.

  10. Home-based step training using videogame technology in people with Parkinson's disease: a single-blinded randomised controlled trial.

    Science.gov (United States)

    Song, Jooeun; Paul, Serene S; Caetano, Maria Joana D; Smith, Stuart; Dibble, Leland E; Love, Rachelle; Schoene, Daniel; Menant, Jasmine C; Sherrington, Cathie; Lord, Stephen R; Canning, Colleen G; Allen, Natalie E

    2018-03-01

    To determine whether 12-week home-based exergame step training can improve stepping performance, gait and complementary physical and neuropsychological measures associated with falls in Parkinson's disease. A single-blinded randomised controlled trial. Community (experimental intervention), university laboratory (outcome measures). Sixty community-dwelling people with Parkinson's disease. Home-based step training using videogame technology. The primary outcomes were the choice stepping reaction time test and Functional Gait Assessment. Secondary outcomes included physical and neuropsychological measures associated with falls in Parkinson's disease, number of falls over six months and self-reported mobility and balance. Post intervention, there were no differences between the intervention ( n = 28) and control ( n = 25) groups in the primary or secondary outcomes except for the Timed Up and Go test, where there was a significant difference in favour of the control group ( P = 0.02). Intervention participants reported mobility improvement, whereas control participants reported mobility deterioration-between-group difference on an 11-point scale = 0.9 (95% confidence interval: -1.8 to -0.1, P = 0.03). Interaction effects between intervention and disease severity on physical function measures were observed ( P = 0.01 to P = 0.08) with seemingly positive effects for the low-severity group and potentially negative effects for the high-severity group. Overall, home-based exergame step training was not effective in improving the outcomes assessed. However, the improved physical function in the lower disease severity intervention participants as well as the self-reported improved mobility in the intervention group suggest home-based exergame step training may have benefits for some people with Parkinson's disease.

  11. Toward FRP-Based Brain-Machine Interfaces-Single-Trial Classification of Fixation-Related Potentials.

    Directory of Open Access Journals (Sweden)

    Andrea Finke

    Full Text Available The co-registration of eye tracking and electroencephalography provides a holistic measure of ongoing cognitive processes. Recently, fixation-related potentials have been introduced to quantify the neural activity in such bi-modal recordings. Fixation-related potentials are time-locked to fixation onsets, just like event-related potentials are locked to stimulus onsets. Compared to existing electroencephalography-based brain-machine interfaces that depend on visual stimuli, fixation-related potentials have the advantages that they can be used in free, unconstrained viewing conditions and can also be classified on a single-trial level. Thus, fixation-related potentials have the potential to allow for conceptually different brain-machine interfaces that directly interpret cortical activity related to the visual processing of specific objects. However, existing research has investigated fixation-related potentials only with very restricted and highly unnatural stimuli in simple search tasks while participant's body movements were restricted. We present a study where we relieved many of these restrictions while retaining some control by using a gaze-contingent visual search task. In our study, participants had to find a target object out of 12 complex and everyday objects presented on a screen while the electrical activity of the brain and eye movements were recorded simultaneously. Our results show that our proposed method for the classification of fixation-related potentials can clearly discriminate between fixations on relevant, non-relevant and background areas. Furthermore, we show that our classification approach generalizes not only to different test sets from the same participant, but also across participants. These results promise to open novel avenues for exploiting fixation-related potentials in electroencephalography-based brain-machine interfaces and thus providing a novel means for intuitive human-machine interaction.

  12. Air charged and microtip catheters cannot be used interchangeably for urethral pressure measurement: a prospective, single-blind, randomized trial.

    Science.gov (United States)

    Zehnder, Pascal; Roth, Beat; Burkhard, Fiona C; Kessler, Thomas M

    2008-09-01

    We determined and compared urethral pressure measurements using air charged and microtip catheters in a prospective, single-blind, randomized trial. A consecutive series of 64 women referred for urodynamic investigation underwent sequential urethral pressure measurements using an air charged and a microtip catheter in randomized order. Patients were blinded to the type and sequence of catheter used. Agreement between the 2 catheter systems was assessed using the Bland and Altman 95% limits of agreement method. Intraclass correlation coefficients of air charged and microtip catheters for maximum urethral closure pressure at rest were 0.97 and 0.93, and for functional profile length they were 0.9 and 0.78, respectively. Pearson's correlation coefficients and Lin's concordance coefficients of air charged and microtip catheters were r = 0.82 and rho = 0.79 for maximum urethral closure pressure at rest, and r = 0.73 and rho = 0.7 for functional profile length, respectively. When applying the Bland and Altman method, air charged catheters gave higher readings than microtip catheters for maximum urethral closure pressure at rest (mean difference 7.5 cm H(2)O) and functional profile length (mean difference 1.8 mm). There were wide 95% limits of agreement for differences in maximum urethral closure pressure at rest (-24.1 to 39 cm H(2)O) and functional profile length (-7.7 to 11.3 mm). For urethral pressure measurement the air charged catheter is at least as reliable as the microtip catheter and it generally gives higher readings. However, air charged and microtip catheters cannot be used interchangeably for clinical purposes because of insufficient agreement. Hence, clinicians should be aware that air charged and microtip catheters may yield completely different results, and these differences should be acknowledged during clinical decision making.

  13. Telephone-delivered psychoeducational intervention for Hong Kong Chinese dementia caregivers: a single-blinded randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kwok T

    2013-09-01

    Full Text Available Timothy Kwok,1,2 Bel Wong,2 Isaac Ip,2 Kenny Chui,2 Daniel Young,2 Florence Ho2 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region; 2Jockey Club Centre for Positive Ageing, Hong Kong, Special Administrative Region Purpose: Many family caregivers of persons with dementia (PWD are unable to participate in community center-based caregiver support services because of logistical constraints. This study evaluated the effectiveness of a telephone-delivered psychoeducational intervention for family caregivers of PWD in alleviating caregiver burden and enhancing caregiving self-efficacy. Subjects and methods: In a single-blinded randomized controlled trial, 38 family caregivers of PWD were randomly allocated into an intervention group or a control group. The intervention group received psychoeducation from a registered social worker over the phone for 12 sessions. Caregivers in the control group were given a DVD containing educational information about dementia caregiving. Outcomes of the intervention were measured by the Chinese versions of the Zarit Burden Interview and the Revised Scale for Caregiving Self-efficacy. Mann–Whitney U tests were used to compare the differences between the intervention and control groups. Results: The level of burden of caregivers in the intervention group reduced significantly compared with caregivers in the control group. Caregivers in the intervention group also reported significantly more gain in self-efficacy in obtaining respite than the control group. Conclusion: A structured telephone intervention can benefit dementia caregivers in terms of self-efficacy and caregiving burden. The limitations of the research and recommendations for intervention are discussed. Keywords: telephone intervention, psychoeducation, dementia caregivers

  14. Mind the gap in clinical trials: A participatory action analysis with citizen collaborators.

    Science.gov (United States)

    Price, Amy; Liew, Su May; Kirkpatrick, Jo; Price, Jazmin; Lopreto, Taylor; Nelken, Yasmin

    2017-02-01

    What are the strengths, gaps, expectations, and barriers to research engagement in clinical trials as communicated through social media? Clinical trials test treatments to provide reliable information for safety and effectiveness. Trials are building blocks in which what is learned in earlier research can be used to improve treatments, compare alternatives, and improve quality of life. For 20 years, the percentages of clinical trials volunteers have decreased whereas the costs of running clinical trials have multiplied. Participants enroll in trials to access latest treatments, to help others, and to advance science, but there is growing unrest. The priorities of those running the trials differ from those of the participants, and the roles for public research involvement lack clarity. Changes to bridge these gaps in the research culture are proposed through the use of participatory action research (PAR) in which stakeholders collaborate to improve research methodology, galvanize citizen participation, multiply health knowledge, problem-solve barriers to access, and explore the value of research volunteers as collaborators. PAR enabled the inclusion of citizens as full collaborators. Social media data were gathered for 120 days until saturation was reached. De-identified data were organized into a Strengths Weaknesses, Opportunities and Threats framework and coded into themes for analysis. After the analysis, the authors prioritized potential solutions for improving research engagement. Strengths and opportunities remained constant through trial phases, disease burdens, and interventions. Threats included alienation, litigation, disparity, and shaming. Poor management and barriers to inclusion were identified as weaknesses. Opportunities included improving resource management and information quality. Barriers were minimized when relationships between staff and participants were inclusive, respectful, tolerant, and open to change. Participants' communications

  15. Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis.

    Science.gov (United States)

    Uthman, Olalekan A; van der Windt, Danielle A; Jordan, Joanne L; Dziedzic, Krysia S; Healey, Emma L; Peat, George M; Foster, Nadine E

    2014-11-01

    Which types of exercise intervention are most effective in relieving pain and improving function in people with lower limb osteoarthritis? As of 2002 sufficient evidence had accumulated to show significant benefit of exercise over no exercise. An approach combining exercises to increase strength, flexibility, and aerobic capacity is most likely to be effective for relieving pain and improving function. Current international guidelines recommend therapeutic exercise (land or water based) as "core" and effective management of osteoarthritis. Evidence from this first network meta-analysis, largely based on studies in knee osteoarthritis, indicates that an intervention combining strengthening exercises with flexibility and aerobic exercise is most likely to improve outcomes of pain and function. Further trials of exercise versus no exercise are unlikely to overturn this positive result. 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.

  16. Antipyretic therapy in critically ill patients with established sepsis: a trial sequential analysis.

    Directory of Open Access Journals (Sweden)

    Zhongheng Zhang

    Full Text Available antipyretic therapy for patients with sepsis has long been debated. The present study aimed to explore the beneficial effect of antipyretic therapy for ICU patients with sepsis.systematic review and trial sequential analysis of randomized controlled trials.Pubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014.Mortality was dichotomized as binary outcome variable and odds ratio (OR was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients.A total of 6 randomized controlled trials including 819 patients were included into final analysis. Overall, there was no beneficial effect of antipyretic therapy on mortality risk in patients with established sepsis (OR: 1.02, 95% CI: 0.50-2.05. The required information size (IS was 2582 and our analysis has not yet reached half of the IS. The Z-curve did not cross the O'Brien-Fleming α-spending boundary or reach the futility, indicating that the non-significant result was probably due to lack of statistical power.our study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis.

  17. Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

    Science.gov (United States)

    Stapleton, Laura M.; Pituch, Keenan A.; Dion, Eric

    2015-01-01

    This article presents 3 standardized effect size measures to use when sharing results of an analysis of mediation of treatment effects for cluster-randomized trials. The authors discuss 3 examples of mediation analysis (upper-level mediation, cross-level mediation, and cross-level mediation with a contextual effect) with demonstration of the…

  18. The Digital Single Market and Legal Certainty : A Critical Analysis

    NARCIS (Netherlands)

    Castermans, A.G.; Graaff, de R.; Haentjens, M.; Colombi, Ciacchi A.

    2016-01-01

    This chapter critically examines the CESL from the viewpoint of its capability to provide legal certainty for commercial actors. This chapter’s analysis focuses on three important stages in the life cycle of a contract, seen from a business perspective: the scope rules that determine whether the

  19. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials

    Science.gov (United States)

    Swerdlow, Daniel I; Preiss, David; Kuchenbaecker, Karoline B; Holmes, Michael V; Engmann, Jorgen E L; Shah, Tina; Sofat, Reecha; Stender, Stefan; Johnson, Paul C D; Scott, Robert A; Leusink, Maarten; Verweij, Niek; Sharp, Stephen J; Guo, Yiran; Giambartolomei, Claudia; Chung, Christina; Peasey, Anne; Amuzu, Antoinette; Li, KaWah; Palmen, Jutta; Howard, Philip; Cooper, Jackie A; Drenos, Fotios; Li, Yun R; Lowe, Gordon; Gallacher, John; Stewart, Marlene C W; Tzoulaki, Ioanna; Buxbaum, Sarah G; van der A, Daphne L; Forouhi, Nita G; Onland-Moret, N Charlotte; van der Schouw, Yvonne T; Schnabel, Renate B; Hubacek, Jaroslav A; Kubinova, Ruzena; Baceviciene, Migle; Tamosiunas, Abdonas; Pajak, Andrzej; Topor-Madry, Romanvan; Stepaniak, Urszula; Malyutina, Sofia; Baldassarre, Damiano; Sennblad, Bengt; Tremoli, Elena; de Faire, Ulf; Veglia, Fabrizio; Ford, Ian; Jukema, J Wouter; Westendorp, Rudi G J; de Borst, Gert Jan; de Jong, Pim A; Algra, Ale; Spiering, Wilko; der Zee, Anke H Maitland-van; Klungel, Olaf H; de Boer, Anthonius; Doevendans, Pieter A; Eaton, Charles B; Robinson, Jennifer G; Duggan, David; Kjekshus, John; Downs, John R; Gotto, Antonio M; Keech, Anthony C; Marchioli, Roberto; Tognoni, Gianni; Sever, Peter S; Poulter, Neil R; Waters, David D; Pedersen, Terje R; Amarenco, Pierre; Nakamura, Haruo; McMurray, John J V; Lewsey, James D; Chasman, Daniel I; Ridker, Paul M; Maggioni, Aldo P; Tavazzi, Luigi; Ray, Kausik K; Seshasai, Sreenivasa Rao Kondapally; Manson, JoAnn E; Price, Jackie F; Whincup, Peter H; Morris, Richard W; Lawlor, Debbie A; Smith, George Davey; Ben-Shlomo, Yoav; Schreiner, Pamela J; Fornage, Myriam; Siscovick, David S; Cushman, Mary; Kumari, Meena; Wareham, Nick J; Verschuren, W M Monique; Redline, Susan; Patel, Sanjay R; Whittaker, John C; Hamsten, Anders; Delaney, Joseph A; Dale, Caroline; Gaunt, Tom R; Wong, Andrew; Kuh, Diana; Hardy, Rebecca; Kathiresan, Sekar; Castillo, Berta A; van der Harst, Pim; Brunner, Eric J; Tybjaerg-Hansen, Anne; Marmot, Michael G; Krauss, Ronald M; Tsai, Michael; Coresh, Josef; Hoogeveen, Ronald C; Psaty, Bruce M; Lange, Leslie A; Hakonarson, Hakon; Dudbridge, Frank; Humphries, Steve E; Talmud, Philippa J; Kivimäki, Mika; Timpson, Nicholas J; Langenberg, Claudia; Asselbergs, Folkert W; Voevoda, Mikhail; Bobak, Martin; Pikhart, Hynek; Wilson, James G; Reiner, Alex P; Keating, Brendan J; Hingorani, Aroon D; Sattar, Naveed

    2015-01-01

    Summary Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05–0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18–0·43), waist circumference (0·32 cm, 0·16–0·47), plasma insulin concentration (1·62%, 0·53–2·72), and plasma glucose concentration (0·23%, 0·02–0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00–1·05); the rs12916-T allele association was consistent (1·06, 1·03–1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18–1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10–0·38 in all trials; 0·33 kg, 95% CI 0·24–0·42 in placebo or standard care controlled trials and −0·15 kg, 95% CI −0·39 to 0·08 in intensive

  20. Numerical Analysis of Hydrodynamic Flow in Microfluidic Biochip for Single-Cell Trapping Application

    Directory of Open Access Journals (Sweden)

    Amelia Ahmad Khalili

    2015-11-01

    Full Text Available Single-cell analysis has become the interest of a wide range of biological and biomedical engineering research. It could provide precise information on individual cells, leading to important knowledge regarding human diseases. To perform single-cell analysis, it is crucial to isolate the individual cells before further manipulation is carried out. Recently, microfluidic biochips have been widely used for cell trapping and single cell analysis, such as mechanical and electrical detection. This work focuses on developing a finite element simulation model of single-cell trapping system for any types of cells or particles based on the hydrodynamic flow resistance (Rh manipulations in the main channel and trap channel to achieve successful trapping. Analysis is carried out using finite element ABAQUS-FEA™ software. A guideline to design and optimize single-cell trapping model is proposed and the example of a thorough optimization analysis is carried out using a yeast cell model. The results show the finite element model is able to trap a single cell inside the fluidic environment. Fluid’s velocity profile and streamline plots for successful and unsuccessful single yeast cell trapping are presented according to the hydrodynamic concept. The single-cell trapping model can be a significant important guideline in designing a new chip for biomedical applications.

  1. Changing cluster composition in cluster randomised controlled trials: design and analysis considerations

    Science.gov (United States)

    2014-01-01

    Background There are many methodological challenges in the conduct and analysis of cluster randomised controlled trials, but one that has received little attention is that of post-randomisation changes to cluster composition. To illustrate this, we focus on the issue of cluster merging, considering the impact on the design, analysis and interpretation of trial outcomes. Methods We explored the effects of merging clusters on study power using standard methods of power calculation. We assessed the potential impacts on study findings of both homogeneous cluster merges (involving clusters randomised to the same arm of a trial) and heterogeneous merges (involving clusters randomised to different arms of a trial) by simulation. To determine the impact on bias and precision of treatment effect estimates, we applied standard methods of analysis to different populations under analysis. Results Cluster merging produced a systematic reduction in study power. This effect depended on the number of merges and was most pronounced when variability in cluster size was at its greatest. Simulations demonstrate that the impact on analysis was minimal when cluster merges were homogeneous, with impact on study power being balanced by a change in observed intracluster correlation coefficient (ICC). We found a decrease in study power when cluster merges were heterogeneous, and the estimate of treatment effect was attenuated. Conclusions Examples of cluster merges found in previously published reports of cluster randomised trials were typically homogeneous rather than heterogeneous. Simulations demonstrated that trial findings in such cases would be unbiased. However, simulations also showed that any heterogeneous cluster merges would introduce bias that would be hard to quantify, as well as having negative impacts on the precision of estimates obtained. Further methodological development is warranted to better determine how to analyse such trials appropriately. Interim recommendations

  2. Analysis of ripple formation in single crystal spot welds

    Energy Technology Data Exchange (ETDEWEB)

    Rappaz, M. [Ecole Polytechnique Federale de Lausanne (Switzerland). Lab de Metallurgie Physique; Corrigan, D.; Boatner, L.A. [Oak Ridge National Lab., TN (United States). Solid State Div.

    1997-10-01

    Stationary spot welds have been made at the (001) surface of Fe-l5%Ni-15%Cr single crystals using a Gas Tungsten Arc (GTA). On the top surface of the spot welds, very regular and concentric ripples were observed after solidification by differential interference color microscopy. Their height (typically 1--5 {micro}m) and spacing (typically {approximately} 60 {micro}m) decreased with the radius of the pool. These ripples were successfully accounted for in terms of capillary-wave theory using the fundamental mode frequency f{sub 0} given by the first zero of the zero-order Bessel function. The spacing d between the ripples was then equated to v{sub s}/f{sub 0}, where v{sub s} is the solidification rate. From the measured ripple spacing, the velocity of the pool was deduced as a function of the radius, and this velocity was in good agreement with the results of a heat-flow simulation.

  3. Single Nucleotide Polymorphism Analysis of Protamine Genes in Infertile Men

    Directory of Open Access Journals (Sweden)

    Ahamad Salamian

    2008-01-01

    Full Text Available Background: Single nucleotide polymorphism (SNPs are considered as one of the underlyingcauses of male infertility. Proper sperm chromatin packaging which involves replacement ofhistones with protamines has profound effect on male fertility. Over 20 SNPs have been reportedfor the protamine 1 and 2.Materials and Methods: The aim of this study was to evaluate the frequency of two previouslyreported SNPs using polymerase chain reaction (PCR-restriction fragment length polymorphism(RFLP approach in 35, 96 and 177 normal, oligozoospermic and azoospermic individuals. TheseSNPs are: 1. A base pair substitution (G at position 197 instead of T in protamine type 1 Openreading frame (ORF including untranslated region, which causes an Arg residue change to Serresidue in a highly conserved region. 2. cytidine nucleotide change to thymidine in position of 248of protamine type 2 ORF which caused a nonsense point mutation.Results: The two mentioned SNPs were not present in the studied population, thus concluding thatthese SNPs can not serves as molecular markers for male infertility diagnosis.Conclusion: The results of our study reveal that in a selected Iranian population, the SNP G197Tand C248T are completely absent and are not associated with male infertility and therefore theseSNPs may not represent a molecular marker for genetic diagnosis of male infertility.

  4. Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

    Science.gov (United States)

    Paterson, Charlotte; Karatzias, Thanos; Dickson, Adele; Harper, Sean; Dougall, Nadine; Hutton, Paul

    2018-04-16

    The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and

  5. Headache : The placebo effects in the control groups in randomized clinical trials; An analysis of systematic reviews

    NARCIS (Netherlands)

    de Groot, Femke M.; Voogt-Bode, Annieke; Passchier, Jan; Berger, Marjolein Y.; Koes, Bart W.; Verhagen, Arianne P.

    Objective: The purpose of this study is to describe the effects in the placebo and "no treatment" arms in trials with headache patients. Method: This is a secondary analysis of randomized controlled trials from 8 systematic reviews and selected trials with a "no treatment" or placebo control group.

  6. Antibiotic prophylaxis in hematopoietic stem cell transplantation. A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kimura, Shun-ichi; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Nakasone, Hideki; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Junya; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2014-07-01

    We performed a meta-analysis to evaluate the impact of systemic antibiotic prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients. We collected reports from PubMed, the Cochrane Library, EMBASE, CINAHL, and Web of Science, along with references cited therein. We included prospective, randomized studies on systemic antibiotic prophylaxis in HSCT recipients. Seventeen trials with 1453 autologous and allogeneic HSCT recipients were included. Systemic antibiotic prophylaxis was compared with placebo or no prophylaxis in 10 trials and with non-absorbable antibiotics in two trials. Systemic antibiotics other than fluoroquinolones were evaluated in five of these 12 trials. Four trials evaluated the effect of the addition of antibiotics for gram-positive bacteria to fluoroquinolones. One trial compared two different systemic antibiotic regimens: fluoroquinolones versus trimethoprim-sulfamethoxazole. As a result, systemic antibiotic prophylaxis reduced the incidence of febrile episodes (OR 0.16; 95%CI 0.09-0.30), clinically or microbiologically documented infection (OR 0.38; 95%CI 0.22-0.63) and bacteremia (OR 0.31; 95%CI 0.16-0.59) without significantly affecting all-cause mortality or infection-related mortality. Systemic antibiotic prophylaxis successfully reduced the incidence of infection. However, there was no significant impact on mortality. The clinical benefits of prophylaxis with fluoroquinolones were inconclusive because of the small number of clinical trials evaluated. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  7. A virtual dosimetry audit - Towards transferability of gamma index analysis between clinical trial QA groups.

    Science.gov (United States)

    Hussein, Mohammad; Clementel, Enrico; Eaton, David J; Greer, Peter B; Haworth, Annette; Ishikura, Satoshi; Kry, Stephen F; Lehmann, Joerg; Lye, Jessica; Monti, Angelo F; Nakamura, Mitsuhiro; Hurkmans, Coen; Clark, Catharine H

    2017-12-01

    Quality assurance (QA) for clinical trials is important. Lack of compliance can affect trial outcome. Clinical trial QA groups have different methods of dose distribution verification and analysis, all with the ultimate aim of ensuring trial compliance. The aim of this study was to gain a better understanding of different processes to inform future dosimetry audit reciprocity. Six clinical trial QA groups participated. Intensity modulated treatment plans were generated for three different cases. A range of 17 virtual 'measurements' were generated by introducing a variety of simulated perturbations (such as MLC position deviations, dose differences, gantry rotation errors, Gaussian noise) to three different treatment plan cases. Participants were blinded to the 'measured' data details. Each group analysed the datasets using their own gamma index (γ) technique and using standardised parameters for passing criteria, lower dose threshold, γ normalisation and global γ. For the same virtual 'measured' datasets, different results were observed using local techniques. For the standardised γ, differences in the percentage of points passing with γ audit has been an informative step in understanding differences in the verification of measured dose distributions between different clinical trial QA groups. This work lays the foundations for audit reciprocity between groups, particularly with more clinical trials being open to international recruitment. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations.

    Science.gov (United States)

    Jørgensen, Karsten J; Johansen, Helle Krogh; Gøtzsche, Peter C

    2006-01-19

    We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before.

  9. Progesterone Therapy for the Prevention of Preterm Labor in Women with Single Risk-factor: A Systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    Kefayat Chaman-Ara

    2016-04-01

    Full Text Available Background: Preterm labor is a common complication of pregnancy which has become a main health concern around the world due to its negative consequences. Objective: To investigate the efficacy of progesterone therapy in the prevention of preterm labor in women with single risk factor. Search strategy: A PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Science Direct, Scopus, OVID, EMBASE, SID, Magiran and Google Scholar search (date last searched April 2016 without any time, language and location restriction was done. Inclusion criteria: All randomized clinical trials of singleton pregnancies with single risk factor (prior preterm labor without short cervical length or short cervical length without prior preterm labor which were randomized to progesterone and control groups were included in our meta-analysis. Primary outcome: Our primary outcome was gestational age at delivery. Results: 13 studies (1259 subjects and 2653 control women were included in the meta-analysis. Using random effect model showed that mean gestational age at delivery of progesterone group is 0.74 (0.41-1.06 month longer than that of control group with CI=95% which is significant statically. Conclusions: Progesterone therapy is an effective intervention for the prevention of preterm labor in women with single risk factor. 

  10. Symposium on single cell analysis and genomic approaches, Experimental Biology 2017 Chicago, Illinois, April 23, 2017.

    Science.gov (United States)

    Coller, Hilary A

    2017-09-01

    Emerging technologies for the analysis of genome-wide information in single cells have the potential to transform many fields of biology, including our understanding of cell states, the response of cells to external stimuli, mosaicism, and intratumor heterogeneity. At Experimental Biology 2017 in Chicago, Physiological Genomics hosted a symposium in which five leaders in the field of single cell genomics presented their recent research. The speakers discussed emerging methodologies in single cell analysis and critical issues for the analysis of single cell data. Also discussed were applications of single cell genomics to understanding the different types of cells within an organism or tissue and the basis for cell-to-cell variability in response to stimuli. Copyright © 2017 the American Physiological Society.

  11. "Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1 trials in the UK

    Directory of Open Access Journals (Sweden)

    Woolhead Gillian

    2007-03-01

    Full Text Available Abstract Background The n-of-1 trial offers a more methodologically sound approach to determining optimum treatment for an individual patient than "trials of therapy" routinely conducted in clinical practice. However, such methodology is rarely used in the UK. This pilot study explores the acceptability of n-of-1 trials to patients in the UK. Methods Patients with osteoarthritis of the knee were recruited to their own 12-week n-of-1 trial comparing either two knee supports or an NSAID with simple analgesic. Patients were interviewed at the start and completion of their trial to explore reasons for participation, understanding of the trial design and experiences of participation. Daily diaries were completed to inform future treatment. Results Nine patients participated (5 supports, 4 drugs. Patients were keen to participate, believing that the trial may lead to personal gains such as improved symptom control and quality of life. However, recruitment to the pharmacological comparison was more difficult since this could also entail risk. All patients were eager to complete the trial, even when difficulties were encountered. Completing the daily diary provided some patients with greater insight into their condition, which allowed them to improve their self-management. The n-of-1 trial design was viewed as a 'logical' design offering an efficient method of reaching a personalised treatment decision tailored to suit individual needs and preferences. Conclusion This pilot study suggests that patients perceive the n-of-1 trial as an acceptable approach to the individualisation of treatment. In addition, further benefits over and above any gained from the interventions can be derived from involvement in such a study.

  12. The patient general satisfaction of mandibular single-implant overdentures and conventional complete dentures: Study protocol for a randomized crossover trial.

    Science.gov (United States)

    Kanazawa, Manabu; Tanoue, Mariko; Miyayasu, Anna; Takeshita, Shin; Sato, Daisuke; Asami, Mari; Lam, Thuy Vo; Thu, Khaing Myat; Oda, Ken; Komagamine, Yuriko; Minakuchi, Shunsuke; Feine, Jocelyne

    2018-05-01

    Mandibular overdentures retained by a single implant placed in the midline of edentulous mandible have been reported to be more comfortable and function better than complete dentures. Although single-implant overdentures are still more costly than conventional complete dentures, there are a few studies which investigated whether mandibular single-implant overdentures are superior to complete dentures when patient general satisfaction is compared. The aim of this study is to assess patient general satisfaction with mandibular single-implant overdentures and complete dentures. This study is a randomized crossover trial to compare mandibular single-implant overdentures and complete dentures in edentulous individuals. Participant recruitment is ongoing at the time of this submission. Twenty-two participants will be recruited. New mandibular complete dentures will be fabricated. A single implant will be placed in the midline of the edentulous mandible. The mucosal surface of the complete denture around the implant will be relieved for 3 months. The participants will then be randomly allocated into 2 groups according to the order of the interventions; group 1 will receive single-implant overdentures first and will wear them for 2 months, followed by complete dentures for 2 months. Group 2 will receive the same treatments in a reverse order. After experiencing the 2 interventions, the participants will choose one of the mandibular prostheses, and yearly follow-up visits are planned for 5 years. The primary outcome of this trial is patient ratings of general satisfaction on 100 mm visual analog scales. Assessments of the prostheses and oral health-related quality of life will also be recorded as patient-reported outcomes. The secondary outcomes are cost and time for treatment. Masticatory efficiency and cognitive capacity will also be recorded. Furthermore, qualitative research will be performed to investigate the factors associated with success of these mandibular

  13. Structured triglyceride for parenteral nutrition: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhou, Yong; Wu, Xiao-Ting; Li, Ni; Zhuang, Wen; Liu, Guanjian; Wu, Taixiang; Wei, Mao-Ling

    2006-01-01

    This study assessed the safety and efficacy of structured triglyceride (ST) for parenteral nutrition. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in March 2005. Language was restricted to Chinese and English. Literature references were checked at the same time. Only RCTs were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of triglyceride (LCT), and the combined results showed that the ST had significant effect on resting energy expenditure (weighted mean difference [WMD] =1.54, 95%CI [ 1.26, 1.82], ptriglycerides (WMD = -0.10, 95%CI [-0.30, 0.10], P=0.32). Only two RCTs compared ST with the physical mixture of medium- and long-chain triglyceride (MCT/LCT), data from trials were not combined due to clinical differences between trials, and conclusions can not be drew from the present data. ST appeared to be safe and well tolerated. Further trials are required, especially compared with the MCT/LCT, with sufficient size and rigorous design.

  14. Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Holte, Kathrine; Krag, Aleksander; Gluud, Lise Lotte

    2012-01-01

    Aim:  The objective of this systematic review and meta-analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods:  Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation...... Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure...... was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I(2) . Results:  Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly...

  15. Microscopic analysis on showers recorded as single core on X-ray films

    International Nuclear Information System (INIS)

    Amato, N.M.; Arata, N.; Maldonado, R.H.C.

    1983-01-01

    Cosmic-ray particles recorded as single dark spots on X-ray films with use of the emulsion chamber data of Brazil-Japan Collaboration are studied. Some results of microscopic analysis of such single-core-like showers on nuclear emulsion plates are reported. (Author) [pt

  16. Manipulation and analysis of a single dopant atom in GaAs

    NARCIS (Netherlands)

    Wijnheijmer, A.P.

    2011-01-01

    This thesis focuses on the manipulation and analysis of single dopant atoms in GaAs by scanning tunneling microscopy (STM) and spectroscopy (STS) at low temperatures. The observation of ionization rings is one of the key results, showing that we can control the charge state of a single dopant atom

  17. Quantitative Synthesis and Component Analysis of Single-Participant Studies on the Picture Exchange Communication System

    Science.gov (United States)

    Tincani, Matt; Devis, Kathryn

    2011-01-01

    The "Picture Exchange Communication System" (PECS) has emerged as the augmentative communication intervention of choice for individuals with autism spectrum disorder (ASD), with a supporting body of single-participant studies. This report describes a meta-analysis of 16 single-participant studies on PECS with percentage of nonoverlapping data…

  18. Stress Analysis of Single Spacer Grid Support considering Fuel Rod

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Y. G.; Jung, D. H.; Kim, J. H. [Chungnam National University, Daejeon (Korea, Republic of); Park, J. K.; Jeon, K. L. [Korea Nuclear Fuel, Daejeon (Korea, Republic of)

    2010-10-15

    Pressurized water reactor (PWR) nuclear fuel assembly is mainly composed of a top-end piece, a bottom-end piece, lots of fuel rods, and several spacer grids. Among them, the main function of spacer grid is protecting fuel rods from Fluid Induced Vibration (FIV). The cross section of spacer grid assembled by laser welding in upper and lower point. When the fuel rod inserted in spacer gird, spring and dimple and around of welded area got a stresses. The main hypothesis of this analysis is the boundary area of HAZ and base metal can get a lot of damage than other area by FIV. So, design factors of spacer grid mainly considered to preventing the fatigue failure in HAZ and spring and dimple of spacer grid. From previous researching, the environment in reactor verified. Pressure and temperature of light water observed 15MPa and 320 .deg. C, and vibration of the fuel rod observed within 0 {approx} 50Hz. In this study, mechanical properties of zirconium alloy that extracted from the test and the spacer grid model which used in the PWR were applied in stress analyzing. General-purpose finite element analysis program was used ANSYS Workbench 12.0.1 version. 3-D CAD program CATIA was used to create spacer grid model

  19. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    John T Kissel

    Full Text Available BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA might benefit patients with spinal muscular atrophy (SMA. The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend, timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP, handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

  20. Essentials of single-cell analysis concepts, applications and future prospects

    CERN Document Server

    Santra, Tuhin

    2016-01-01

    This book provides an overview of single-cell isolation, separation, injection, lysis and dynamics analysis as well as a study of their heterogeneity using different miniaturized devices. As an important part of single-cell analysis, different techniques including electroporation, microinjection, optical trapping, optoporation, rapid electrokinetic patterning and optoelectronic tweezers are described in detail. It presents different fluidic systems (e.g. continuous micro/nano-fluidic devices, microfluidic cytometry) and their integration with sensor technology, optical and hydrodynamic stretchers etc., and demonstrates the applications of single-cell analysis in systems biology, proteomics, genomics, epigenomics, cancer transcriptomics, metabolomics, biomedicine and drug delivery systems. It also discusses the future challenges for single-cell analysis, including the advantages and limitations. This book is enjoyable reading material while at the same time providing essential information to scientists in acad...

  1. Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

    Science.gov (United States)

    Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

    2017-09-01

    Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

  2. Analysis of photoluminescence spectra of lead-tungstate single crystals

    International Nuclear Information System (INIS)

    Kim, Do Hyung; Lee, Sang Yun; Lee, Myoung Bok

    2003-01-01

    In addition to the intrinsic blue emission band near 430 nm for an ideal PbWO 4 scheelite structure, the presence of three extra emission bands peaking near blue-green and green-red colors was clearly identified for thermally synthesized bulk crystals with the help of a reliable fitting process applicable for microscopic analysis of recorded PL spectra. The origin, nature, and electro-optical behaviors of the extra emission bands are strongly related to the structural change from an ideal scheelite to modified ones, so now we can more closely track down the nature and the relevant behaviors, which are still in dispute, of the apparent colors of the PbWO 4 scintillating medium by constructing structural models and by considering the energy transfer mechanism between the color centers

  3. Interconnecting smartphone, image analysis server, and case report forms in clinical trials for automatic skin lesion tracking in clinical trials

    Science.gov (United States)

    Haak, Daniel; Doma, Aliaa; Gombert, Alexander; Deserno, Thomas M.

    2016-03-01

    Today, subject's medical data in controlled clinical trials is captured digitally in electronic case report forms (eCRFs). However, eCRFs only insufficiently support integration of subject's image data, although medical imaging is looming large in studies today. For bed-side image integration, we present a mobile application (App) that utilizes the smartphone-integrated camera. To ensure high image quality with this inexpensive consumer hardware, color reference cards are placed in the camera's field of view next to the lesion. The cards are used for automatic calibration of geometry, color, and contrast. In addition, a personalized code is read from the cards that allows subject identification. For data integration, the App is connected to an communication and image analysis server that also holds the code-study-subject relation. In a second system interconnection, web services are used to connect the smartphone with OpenClinica, an open-source, Food and Drug Administration (FDA)-approved electronic data capture (EDC) system in clinical trials. Once the photographs have been securely stored on the server, they are released automatically from the mobile device. The workflow of the system is demonstrated by an ongoing clinical trial, in which photographic documentation is frequently performed to measure the effect of wound incision management systems. All 205 images, which have been collected in the study so far, have been correctly identified and successfully integrated into the corresponding subject's eCRF. Using this system, manual steps for the study personnel are reduced, and, therefore, errors, latency and costs decreased. Our approach also increases data security and privacy.

  4. Combined EGFR and VEGFR versus single EGFR signaling pathways inhibition therapy for NSCLC: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xinji Zhang

    Full Text Available BACKGROUND: Lung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR, progression-free survival (PFS, overall survival (OS and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets. Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89-1.05; P=0.472. Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67-0.95; P=0.011. There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95-2.18; P=0.085. Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy. CONCLUSIONS: There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination

  5. Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

    Science.gov (United States)

    Leurent, Baptiste; Gomes, Manuel; Carpenter, James R

    2018-06-01

    Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption. © 2018 The Authors Health Economics published by John Wiley & Sons Ltd.

  6. Garlic powder intake and cardiovascular risk factors: a meta-analysis of randomized controlled clinical trials.

    Science.gov (United States)

    Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik; Kwon, Oran

    2014-12-01

    Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD risk factors. We searched PubMed, Cochrane, Science Direct and EMBASE through May 2014. A random-effects meta-analysis was performed on 22 trials reporting total cholesterol (TC), 17 trials reporting LDL cholesterol (LDL-C), 18 trials reporting HDL cholesterol (HDL-C), 4 trials reporting fasting blood glucose (FBG), 9 trials reporting systolic blood pressure (SBP) and 10 trials reporting diastolic blood pressure (DBP). The overall garlic powder intake significantly reduced blood TC and LDL-C by -0.41 mmol/L (95% confidence interval [CI], -0.69, -0.12) (-15.83 mg/dL [95% CI, -26.64, -4.63]) and -0.21 mmol/L (95% CI, -0.40, -0.03) (-8.11 mg/dL [95% CI, -15.44, -1.16]), respectively. The mean difference in the reduction of FBG levels was -0.96 mmol/L (95% CI, -1.91, -0.01) (-17.30 mg/dL [95% CI, -34.41, -0.18]). Evidence for SBP and DBP reduction in the garlic supplementation group was also demonstrated by decreases of -4.34 mmHg (95% CI, -8.38, -0.29) and -2.36 mmHg (95% CI, -4.56, -0.15), respectively. This meta-analysis provides consistent evidence that garlic powder intake reduces the CVD risk factors of TC, LDL-C, FBG and BP.

  7. Long Detection Programming in Single-Chamber Defibrillators Reduces Unnecessary Therapies and Mortality: The ADVANCE III Trial.

    Science.gov (United States)

    Gasparini, Maurizio; Lunati, Maurizio G; Proclemer, Alessandro; Arenal, Angel; Kloppe, Axel; Martínez Ferrer, Josè B; Hersi, Ahmad S; Gulaj, Marcin; Wijffels, Maurits C E; Santi, Elisabetta; Manotta, Laura; Varma, Niraj

    2017-11-01

    This study sought to evaluate the effects of programming a long detection in single-chamber (VVI) implantable cardioverter-defibrillators (ICDs) in the multicenter prospective ADVANCE III (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III) trial. Programming strategies may reduce unnecessary ICD shocks and their adverse effects but to date have been described only for dual-chamber ICDs. A total of 545 subjects (85% male; atrial fibrillation 25%, left ventricular ejection fraction 31%, ischemic etiology 68%, secondary prevention indications 32%) receiving a VVI ICD were randomized to long detection (30 of 40 intervals) or standard programming (18 of 24 intervals) based on device type, atrial fibrillation history, and indication. In both arms, antitachycardia pacing (ATP) therapy during charging was programmed for episodes with cycle length 320 to 200 ms and shock only for cycle length functions enabled. Therapies delivered were compared using a negative binomial regression model. A total of 267 patients were randomized to long detection and 278 to the control group. Median follow-up was 12 months. One hundred twelve therapies (shocks and ATP) occurred in the long detection arm versus 257 in the control arm, for a 48% reduction with 30 of 40 intervals (95% confidence interval [CI]: 0.36 to 0.76; p = 0.002). In the long detection arm, overall shocks were reduced by 40% compared to the control arm (48 vs. 24; 95% CI: 0.38 to 0.94; p = 0.026) and appropriate shocks by 51% (34 vs. 74; 95% CI: 0.26 to 0.94; p = 0.033). Syncopal events did not differ between arms, but survival improved in the long detection arm. Among patients implanted with a VVI ICD, programming with the long detection interval significantly reduced appropriate therapies, shocks, and all-cause mortality. (Avoid DeliVering TherApies for Non-sustained Arrhythmias in ICD PatiEnts III [ADVANCEIII]; NCT00617175). Copyright © 2017 The Authors. Published by Elsevier Inc. All

  8. Effects of single-shot and steady-state propofol anaesthesia on rocuronium dose-response relationship: a randomised trial.

    Science.gov (United States)

    Stäuble, C G; Stäuble, R B; Schaller, S J; Unterbuchner, C; Fink, H; Blobner, M

    2015-08-01

    Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration. After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of propofol, n = 36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16. A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30 min of propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose-response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2 min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg (0.296-0.520)]. The ED50 were not different between groups. The potency of rocuronium was significantly enhanced after propofol infusion for 30 min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Measuring skin necrosis in a randomised controlled feasibility trial of heat preconditioning on wound healing after reconstructive breast surgery: study protocol and statistical analysis plan for the PREHEAT trial.

    Science.gov (United States)

    Cro, Suzie; Mehta, Saahil; Farhadi, Jian; Coomber, Billie; Cornelius, Victoria

    2018-01-01

    Essential strategies are needed to help reduce the number of post-operative complications and associated costs for breast cancer patients undergoing reconstructive breast surgery. Evidence suggests that local heat preconditioning could help improve the provision of this procedure by reducing skin necrosis. Before testing the effectiveness of heat preconditioning in a definitive randomised controlled trial (RCT), we must first establish the best way to measure skin necrosis and estimate the event rate using this definition. PREHEAT is a single-blind randomised controlled feasibility trial comparing local heat preconditioning, using a hot water bottle, against standard care on skin necrosis among breast cancer patients undergoing reconstructive breast surgery. The primary objective of this study is to determine the best way to measure skin necrosis and to estimate the event rate using this definition in each trial arm. Secondary feasibility objectives include estimating recruitment and 30 day follow-up retention rates, levels of compliance with the heating protocol, length of stay in hospital and the rates of surgical versus conservative management of skin necrosis. The information from these objectives will inform the design of a larger definitive effectiveness and cost-effectiveness RCT. This article describes the PREHEAT trial protocol and detailed statistical analysis plan, which includes the pre-specified criteria and process for establishing the best way to measure necrosis. This study will provide the evidence needed to establish the best way to measure skin necrosis, to use as the primary outcome in a future RCT to definitively test the effectiveness of local heat preconditioning. The pre-specified statistical analysis plan, developed prior to unblinded data extraction, sets out the analysis strategy and a comparative framework to support a committee evaluation of skin necrosis measurements. It will increase the transparency of the data analysis for the

  10. Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

    Science.gov (United States)

    Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

    2011-01-01

    Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

  11. Retrospective analysis of paediatric achalasia in India: Single centre experience

    Directory of Open Access Journals (Sweden)

    Sunita Singh

    2012-01-01

    Full Text Available Background: Developing countries at tertiary referral centre. The aim of this study was to share our experience of paediatric achalasia in Indian scenario. Materials and Methods: This was a retrospective analysis of children <16 years, operated for achalasia at our centre, from December 1998 to December 2011. Results: Total 40 patients (mean age 39 ± 4.29 months, including 1 patient of megaesophagus were operated over 13 years of period; 17 patients (associated congenital H-type tracheoesophageal fistula in one patient, non- responders/ lost follow-up for minimum of 3 years in 16 patients were excluded from the study. The response rate of parents in follow-up was 60.0%. Mean symptoms duration was 27.88 ± 2 months. Most common symptoms were regurgitation and failure to thrive (78.2%. Mean symptom scoring in follow-up after 3 year was 1 ± 0.7 compared to 5 ± 0.51 at the time of admission (P < 0.012. One infant expired (mediastenitis, one developed adhesive intestinal obstruction and one needed posterior re-myotomy (for megaesophagus. There were no treatment failures in mean follow-up of 40.2 ± 5.07 months. Conclusions: Cardiomyotomy with partial fundoplication is the best modality of treatment for paediatric achalasia cardia, even from parents′ perspective.

  12. Overnight Glucose Control with Dual- and Single-Hormone Artificial Pancreas in Type 1 Diabetes with Hypoglycemia Unawareness: A Randomized Controlled Trial.

    Science.gov (United States)

    Abitbol, Alexander; Rabasa-Lhoret, Remi; Messier, Virginie; Legault, Laurent; Smaoui, Mohamad; Cohen, Nathan; Haidar, Ahmad

    2018-03-01

    The dual-hormone (insulin and glucagon) artificial pancreas may be justifiable in some, but not all, patients. We sought to compare dual- and single-hormone artificial pancreas systems in patients with hypoglycemia unawareness and documented nocturnal hypoglycemia. We conducted a randomized crossover trial comparing the efficacy of dual- and single-hormone artificial pancreas systems in controlling plasma glucose levels over the course of one night's sleep. We recruited 18 adult participants with hypoglycemia unawareness and 17 participants with hypoglycemia awareness, all of whom had documented nocturnal hypoglycemia during 2 weeks of screening. Outcomes were calculated using plasma glucose. In participants with hypoglycemia unawareness, the median (interquartile range [IQR]) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on dual-hormone artificial pancreas nights and 0% (0-10) on single-hormone artificial pancreas nights (P = 0.20). Additionally, participants with hypoglycemia unawareness experienced two hypoglycemic events (dual-hormone artificial pancreas nights and three hypoglycemic events on single-hormone artificial pancreas nights. In participants with hypoglycemia awareness, the median (IQR) percentage of time that plasma glucose was below 4.0 mmol/L was 0% (0-0) on both dual- and single-hormone artificial pancreas nights. Hypoglycemia awareness participants experienced zero hypoglycemic events on dual-hormone artificial pancreas nights and one event on single-hormone artificial pancreas nights. In this study, dual-hormone and single-hormone systems performed equally well in preventing nocturnal hypoglycemia in participants with hypoglycemia unawareness. Longer studies over the course of multiple days and nights may be needed to explore possible specific benefits in this population. ClinicalTrials.gov No. NCT02282254.

  13. Subgroup Analysis of Trials Is Rarely Easy (SATIRE: a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

    Directory of Open Access Journals (Sweden)

    Malaga German

    2009-11-01

    Full Text Available Abstract Background Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1 to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2 to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3 to examine the analysis, and interpretation of subgroup effects for each study's primary outcome. Methods We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes. Discussion A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize

  14. Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

    Science.gov (United States)

    Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

    2009-09-01

    The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to

  15. Cupping therapy versus acupuncture for pain-related conditions: a systematic review of randomized controlled trials and trial sequential analysis.

    Science.gov (United States)

    Zhang, Ya-Jing; Cao, Hui-Juan; Li, Xin-Lin; Yang, Xiao-Ying; Lai, Bao-Yong; Yang, Guo-Yang; Liu, Jian-Ping

    2017-01-01

    Both cupping therapy and acupuncture have been used in China for a long time, and their target indications are pain-related conditions. There is no systematic review comparing the effectiveness of these two therapies. To compare the beneficial effectiveness and safety between cupping therapy and acupuncture for pain-related conditions to provide evidence for clinical practice. Protocol of this review was registered in PROSPERO (CRD42016050986). We conducted literature search from six electronic databases until 31st March 2017. We included randomized trials comparing cupping therapy with acupuncture on pain-related conditions. Methodological quality of the included studies was evaluated by risk of bias tool. Mean difference, risk ratio, risk difference and their 95% confidence interval were used to report the estimate effect of the pooled results through meta-analysis or the results from each individual study. Trial sequential analysis (TSA) was applied to adjust random errors and calculate the sample size. Twenty-three randomized trials with 2845 participants were included covering 12 pain-related conditions. All included studies were of poor methodological quality. Three meta-analyses were conducted, which showed similar clinical beneficial effects of cupping therapy and acupuncture for the rate of symptom improvement in cervical spondylosis (RR 1.13, 95% CI 1.01 to 1.26; n = 646), lateral femoral cutaneous neuritis (RR 1.10, 95% CI 1.00 to 1.22; n = 102) and scapulohumeral periarthritis (RR 1.31, 95% CI 1.15 to 1.51; n = 208). Results from other outcomes (such as visual analogue and numerical rating scale) in each study also showed no statistical significant difference between these two therapies for all included pain-related conditions. The results of TSA for cervical spondylosis demonstrated that the current available data have not reached a powerful conclusion. No serious adverse events related to cupping therapy or acupuncture was found in included

  16. Effects of Daikenchuto on Abdominal Bloating Accompanied by Chronic Constipation: A Prospective, Single-Center Randomized Open Trial

    Directory of Open Access Journals (Sweden)

    Mika Yuki

    2015-12-01

    Conclusions: DKT treatment improved quality of life for patients with chronic constipation regardless of the presence of SIBO and showed no effects on small intestine bacteria. UMIN Clinical Trial Registry identifier: UMIN000008070.

  17. ECL-IAA and ECL-GADA Can Identify High-Risk Single Autoantibody-Positive Relatives in the TrialNet Pathway to Prevention Study.

    Science.gov (United States)

    Steck, Andrea K; Fouts, Alexandra; Miao, Dongmei; Zhao, Zhiyuan; Dong, Fran; Sosenko, Jay; Gottlieb, Peter; Rewers, Marian J; Yu, Liping

    2016-07-01

    Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time. Affinity assays were performed on a subset of single autoantibody-positive subjects at initial and most recent visits. After a mean follow-up of 5.3 years, 20 subjects developed type 1 diabetes. Among either single GADA or single mIAA subjects, those who were positive in the ECL assay showed higher affinity at the initial visit, and affinity results stayed consistent over time. No converting events from low to high or high to low affinity were seen over time. Confirmed positivity for ECL is associated with high affinity and can help staging of risk for type 1 diabetes in single autoantibody-positive subjects.

  18. Medulloblastoma in adults. A retrospective single institution analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hadi, Indrawati; Roengvoraphoj, Olarn; Niyazi, Maximilian; Nachbichler, Silke Birgit [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); Roeder, Falk [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); German Cancer Research Center (DKFZ), Molecular Radiation Oncology, Heidelberg (Germany); Schueller, Ulrich [University Medical Center, Institute of Neuropathology, Hamburg-Eppendorf (Germany); Research Institute Children' s Cancer Center, Hamburg (Germany); University Medical Center, Department of Pediatric Hematology and Oncology, Hamburg-Eppendorf (Germany); Belka, Claus [LMU Munich, Department of Radiation Oncology, University Hospital, Munich (Germany); German Cancer Consortium (DKTK), Munich (Germany)

    2018-03-15

    Adult medulloblastoma is a rare disease treated according to the current pediatric treatment guidelines. This retrospective analysis investigated the clinical outcomes and prognostic factors of adult medulloblastoma patients, who received multimodal therapy at our institution. Treatment charts of all patients over the age of 15 years of age with de novo medulloblastoma, who had been treated at our institution between 2001 and 2014, were retrospectively analyzed. Patients' demographic parameters, initial symptoms, treatment modalities, toxicities, and survival outcomes were investigated. In all, 21 patients with a median age of 30.2 years were identified. The most frequent histologies were desmoplastic and classic, and the most common molecular subtype was sonic hedgehog (SHH). After tumor resection, all patients received craniospinal irradiation (median dose 35.2 Gy) and a boost to the posterior fossa (median dose 19.8 Gy). Simultaneous chemotherapy with vincristine was given to 20 patients and sequential chemotherapy to 15 patients. The most common side effects were hematological toxicities. Median overall survival (OS) has not been reached after a median follow-up of 92 months. Estimated 5- and 10-year OS was 89 and 80%, respectively. Estimated 5- and 10-year progression-free survival (PFS) was 89 and 81%, respectively. In univariate analysis, a shorter interval between tumor resection and end of irradiation was significantly associated with improved OS and PFS, anaplastic histology with worse OS and PFS. The combined modality treatment showed a good outcome in adults with medulloblastoma. Treatment time was revealed to be prognostic and should be kept as short as possible. (orig.) [German] Das Medulloblastom des Erwachsenen ist eine seltene Erkrankung, die analog paediatrischer Behandlungsprotokolle therapiert wird. Diese retrospektive Analyse untersuchte die klinischen Ergebnisse und prognostischen Faktoren von erwachsenen Medulloblastompatienten, die eine

  19. Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

    International Nuclear Information System (INIS)

    Petrelli, Fausto; Comito, Tiziana; Ghidini, Antonio; Torri, Valter; Scorsetti, Marta; Barni, Sandro

    2017-01-01

    Purpose: Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results: A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions: The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.

  20. Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer: A Systematic Review and Pooled Analysis of 19 Trials

    Energy Technology Data Exchange (ETDEWEB)

    Petrelli, Fausto, E-mail: faupe@libero.it [Oncology Unit, Department of Oncology, ASST Bergamo Ovest, Treviglio (Italy); Comito, Tiziana [Department of Radiosurgery and Radiotherapy, Istituto Clinico Humanitas Cancer Center and Research Hospital, Milan (Italy); Ghidini, Antonio [Oncology Unit, Igea Hospital, Milan (Italy); Torri, Valter [Department of Biomedical Sciences, Humanitas University and Radiotherapy and Radiosurgery Department-Humanitas Research Hospital, Milan (Italy); Scorsetti, Marta [Department of Radiosurgery and Radiotherapy, Istituto Clinico Humanitas Cancer Center and Research Hospital, Milan (Italy); Barni, Sandro [Oncology Unit, Department of Oncology, ASST Bergamo Ovest, Treviglio (Italy)

    2017-02-01

    Purpose: Although surgery is the standard of care for resectable pancreatic cancer (PC), standard-dose chemoradiation therapy and chemotherapy alone are suitable for patients with unresectable disease. Stereotactic body radiation therapy (SBRT) is an alternative, focused local therapy that delivers high radiation doses within a few fractions to the cancer, sparing the surrounding critical tissue. We performed a systematic review and pooled analysis of published trials to evaluate the efficacy and safety of this emerging treatment modality. Methods and Materials: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, SCOPUS, the Web of Science, and CINAHL for publications regarding SBRT for locally advanced PC. The 1-year overall survival (OS) rate was the primary endpoint, and the median OS, 2-year OS rate, 1-year locoregional control (LRC) rate, and grade 3 to 4 toxicities were the secondary endpoints. A multivariate random-effects meta-analysis was performed to calculate the aggregated OS rates at 1 and 2 years and the 1-year LRC rate. Results: A total of 19 studies, encompassing 1009 patients, were included in the present analysis. The pooled 1-year OS was 51.6% in 13 trials with data available. The median OS ranged from 5.7 to 47 months (median 17). The LRC rate at 1 year was 72.3%. Overall, the occurrence of severe adverse events did not exceed 10%. LRC appeared to correlate with the total SBRT dose and the number of fractions. Conclusions: The advantages of SBRT in terms of treatment time, satisfactory OS, and LRC indicate that it is an effective option for inoperable PC. However, a definitive validation of this treatment modality in large randomized studies is required, owing to the nonrandomized nature of the included studies and the limitations of small single-center series that include mixed populations.

  1. [Esthetic analysis on immediate single-tooth implant restoration in anterior maxilla].

    Science.gov (United States)

    Li, Shao-wei; Wang, Guo-shi; Sha, Yan-zhi

    2015-10-01

    To evaluate the esthetic outcomes of immediate single-tooth implant restoration in anterior maxilla with the pink esthetic score (PES). Nine patients were treated with 9 Straumann implants by immediate single-tooth implant restoration in anterior maxilla. Assessment of PES after crown placement at 1 week (baseline) and 6 months after implantation was conducted. Statistical analysis was performed using SPSS 16.0 software package. Nine implants achieved a retention rate of 100%. PES for single-tooth implant was 10.33 ± 1.50 at 1 week and 11.44 ± 0.88 at 6 months after crown placement. The difference was significant(P=0.021). This study indicates that immediate single-tooth implant restoration in anterior maxilla is predictable. Immediate single-tooth implantation can result in good clinical esthetic results in most patients with single-tooth missing in anterior maxilla.

  2. Sensitivity Analysis of Per-Protocol Time-to-Event Treatment Efficacy in Randomized Clinical Trials

    Science.gov (United States)

    Gilbert, Peter B.; Shepherd, Bryan E.; Hudgens, Michael G.

    2013-01-01

    Summary Assessing per-protocol treatment effcacy on a time-to-event endpoint is a common objective of randomized clinical trials. The typical analysis uses the same method employed for the intention-to-treat analysis (e.g., standard survival analysis) applied to the subgroup meeting protocol adherence criteria. However, due to potential post-randomization selection bias, this analysis may mislead about treatment efficacy. Moreover, while there is extensive literature on methods for assessing causal treatment effects in compliers, these methods do not apply to a common class of trials where a) the primary objective compares survival curves, b) it is inconceivable to assign participants to be adherent and event-free before adherence is measured, and c) the exclusion restriction assumption fails to hold. HIV vaccine efficacy trials including the recent RV144 trial exemplify this class, because many primary endpoints (e.g., HIV infections) occur before adherence is measured, and nonadherent subjects who receive some of the planned immunizations may be partially protected. Therefore, we develop methods for assessing per-protocol treatment efficacy for this problem class, considering three causal estimands of interest. Because these estimands are not identifiable from the observable data, we develop nonparametric bounds and semiparametric sensitivity analysis methods that yield estimated ignorance and uncertainty intervals. The methods are applied to RV144. PMID:24187408

  3. A meta-analysis of randomised placebo-controlled treatment trials for depression and anxiety in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Lakkhina Troeung

    Full Text Available Psychopharmacotherapy currently constitutes the first-line treatment for depression and anxiety in Parkinson's disease (PD however the efficacy of antidepressant treatments in PD is unclear. Several alternative treatments have been suggested as potentially more viable alternatives including dopamine agonists, repetitive transcranial magnetic stimulation, and cognitive behavioural therapy (CBT.A meta-analysis of randomised placebo-controlled trials for depression and/or anxiety in PD was conducted to systematically examine the efficacy of current treatments for depression and anxiety in PD.Nine trials were included. There was only sufficient data to calculate a pooled effect for antidepressant therapies. The pooled effect of antidepressants for depression in PD was moderate but non-significant (d = .71, 95% CI = -1.33 to 3.08. The secondary effect of antidepressants on anxiety in PD was large but also non-significant (d = 1.13, 95% CI = -.67 to 2.94. Two single-trials of non-pharmacological treatments for depression in PD resulted in significant large effects; Omega-3 supplementation (d = .92, 95% CI = .15 to 1.69 and CBT (d = 1.57, 95% CI = 1.06 to 2.07, and warrant further exploration.There remains a lack of controlled trials for both pharmacological and non-pharmacological treatments for depression and anxiety in PD which limits the conclusions which can be drawn. While the pooled effects of antidepressant therapies in PD were non-significant, the moderate to large magnitude of each pooled effect is promising. Non-pharmacological approaches show potential for depression in PD however more research is required.

  4. Fluidic Logic Used in a Systems Approach to Enable Integrated Single-cell Functional Analysis

    Directory of Open Access Journals (Sweden)

    Naveen Ramalingam

    2016-09-01

    Full Text Available The study of single cells has evolved over the past several years to include expression and genomic analysis of an increasing number of single cells. Several studies have demonstrated wide-spread variation and heterogeneity within cell populations of similar phenotype. While the characterization of these populations will likely set the foundation for our understanding of genomic- and expression-based diversity, it will not be able to link the functional differences of a single cell to its underlying genomic structure and activity. Currently, it is difficult to perturb single cells in a controlled environment, monitor and measure the response due to perturbation, and link these response measurements to downstream genomic and transcriptomic analysis. In order to address this challenge, we developed a platform to integrate and miniaturize many of the experimental steps required to study single-cell function. The heart of this platform is an elastomer-based Integrated Fluidic Circuit (IFC that uses fluidic logic to select and sequester specific single cells based on a phenotypic trait for downstream experimentation. Experiments with sequestered cells that have been performed include on-chip culture, exposure to a variety of stimulants, and post-exposure image-based response analysis, followed by preparation of the mRNA transcriptome for massively parallel sequencing analysis. The flexible system embodies experimental design and execution that enable routine functional studies of single cells.

  5. Clinical trials in allied medical fields: A cross-sectional analysis of World Health Organization International Clinical Trial Registry Platform

    Directory of Open Access Journals (Sweden)

    S. Kannan

    2016-03-01

    Conclusion: The number of clinical trials done in allied fields of medicine other than the allopathic system has lowered down, and furthermore focus is required regarding the methodological quality of these trials and more support from various organizations.

  6. A hierarchy of patient-reported outcome measures for meta-analysis of knee osteoarthritis trials

    DEFF Research Database (Denmark)

    Juhl, Carsten Bogh; Lund, Hans; Guyatt, GH

    2010-01-01

    Title A hierarchy of patient-reported outcome measures for meta-analysis of knee osteoarthritis trials: empirical evidence from a survey of high impact journals Objective To develop a prioritized list for extracting patient-reported outcomes (PROs) measuring pain and disability for meta-analyses ......Title A hierarchy of patient-reported outcome measures for meta-analysis of knee osteoarthritis trials: empirical evidence from a survey of high impact journals Objective To develop a prioritized list for extracting patient-reported outcomes (PROs) measuring pain and disability for meta...... composite disability scores. Conclusions As choosing the most favorable PROs from individual trials can overestimate the effect compared to a systematic approach, using a prioritized list as presented in this study is recommended to reduce reviewer's likelihood of biased selection of PROs in meta-analyses....

  7. Interim analysis: A rational approach of decision making in clinical trial.

    Science.gov (United States)

    Kumar, Amal; Chakraborty, Bhaswat S

    2016-01-01

    Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

  8. Missing data and censoring in the analysis of progression-free survival in oncology clinical trials.

    Science.gov (United States)

    Denne, J S; Stone, A M; Bailey-Iacona, R; Chen, T-T

    2013-01-01

    Progression-free survival (PFS) is increasingly used as a primary endpoint in oncology clinical trials. However, trial conduct is often such that PFS data on some patients may be partially missing either due to incomplete follow-up for progression, or due to data that may be collected but confounded by patients stopping randomized therapy or starting alternative therapy prior to progression. Regulatory guidance on how to handle these patients in the analysis and whether to censor these patients differs between agencies. We present results of a reanalysis of 28 Phase III trials from 12 companies or institutions performed by the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert Team. We show that analyses not adhering to the intention-to-treat principle tend to give hazard ratio estimates further from unity and describe several factors associated with this shift. We present illustrative simulations to support these findings and provide recommendations for the analysis of PFS.

  9. Interim analysis: A rational approach of decision making in clinical trial

    Directory of Open Access Journals (Sweden)

    Amal Kumar

    2016-01-01

    Full Text Available Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

  10. Marine Oil Supplements for Arthritis Pain: A Systematic Review and Meta-Analysis of Randomized Trials

    Directory of Open Access Journals (Sweden)

    Ninna K. Senftleber

    2017-01-01

    Full Text Available Arthritis patients often take fish oil supplements to alleviate symptoms, but limited evidence exists regarding their efficacy. The objective was to evaluate whether marine oil supplements reduce pain and/or improve other clinical outcomes in patients with arthritis. Six databases were searched systematically (24 February 2015. We included randomized trials of oral supplements of all marine oils compared with a control in arthritis patients. The internal validity was assessed using the Cochrane Risk of Bias tool and heterogeneity was explored using restricted maximum of likelihood (REML-based meta-regression analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE was used to rate the overall quality of the evidence. Forty-two trials were included; 30 trials reported complete data on pain. The standardized mean difference (SMD suggested a favorable effect (−0.24; 95% confidence interval, CI, −0.42 to −0.07; heterogeneity, I2 = 63%. A significant effect was found in patients with rheumatoid arthritis (22 trials; −0.21; 95% CI, −0.42 to −0.004 and other or mixed diagnoses (3 trials; −0.63; 95% CI, −1.20 to −0.06, but not in osteoarthritis patients (5 trials; −0.17; 95% CI, −0.57–0.24. The evidence for using marine oil to alleviate pain in arthritis patients was overall of low quality, but of moderate quality in rheumatoid arthritis patients.

  11. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

    Science.gov (United States)

    Federer, Callie; Yoo, Minjae; Tan, Aik Choon

    2016-12-01

    Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

  12. Clinical Marginal and Internal Adaptation of Maxillary Anterior Single All-Ceramic Crowns and 2-year Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Akın, Aslı; Toksavul, Suna; Toman, Muhittin

    2015-07-01

    The aims of this randomized-controlled clinical trial were to compare marginal and internal adaptation of all-ceramic crowns fabricated with CAD/CAM and heat-pressed (HP) techniques before luting and to evaluate the clinical outcomes at baseline and at 6, 12, and 24 months after luting. Fifteen CAD/CAM (CC) and 15 HP all-ceramic crowns were placed in 15 patients. A silicone replica was obtained to measure marginal and internal adaptation of each all-ceramic crown before luting, and they were sectioned buccolingually and mesiodistally. Marginal and internal adaptations were measured using computerized light microscope at 40× magnification. Clinical evaluations took place at baseline (2 days after luting) and at 6, 12, and 24 months after luting. Replica scores were analyzed with Mann-Whitney U and Student's t-test (α = 0.05). Survival rate of crowns was determined using Kaplan-Meier statistical analysis. The median marginal gap for the CC group was 132.2 μm and was 130.2 μm for the HP group. The mean internal adaptation for the CC group was 220.3 ± 51.3 μm and 210.5 ± 31 μm for the HP group. There were no statistically significant differences with respect to marginal opening (Mann-Whitney U test; p = 0.95) and internal adaptation (Student's t-test; p = 0.535) between the 2 groups. Based on modified Ryge criteria, 100% of the crowns were rated satisfactory during the 2-year period. In this in vivo study, CAD/CAM and HP all-ceramic crowns exhibited similar marginal and internal adaptations. A 100% success rate was recorded for the 15 CAD/CAM and for the 15 HP all-ceramic crowns during the 2-year period. © 2014 by the American College of Prosthodontists.

  13. Deviation from intention to treat analysis in randomised trials and treatment effect estimates: meta-epidemiological study.

    Science.gov (United States)

    Abraha, Iosief; Cherubini, Antonio; Cozzolino, Francesco; De Florio, Rita; Luchetta, Maria Laura; Rimland, Joseph M; Folletti, Ilenia; Marchesi, Mauro; Germani, Antonella; Orso, Massimiliano; Eusebi, Paolo; Montedori, Alessandro

    2015-05-27

    To examine whether deviation from the standard intention to treat analysis has an influence on treatment effect estimates of randomised trials. Meta-epidemiological study. Medline, via PubMed, searched between 2006 and 2010; 43 systematic reviews of interventions and 310 randomised trials were included. From each year searched, random selection of 5% of intervention reviews with a meta-analysis that included at least one trial that deviated from the standard intention to treat approach. Basic characteristics of the systematic reviews and randomised trials were extracted. Information on the reporting of intention to treat analysis, outcome data, risk of bias items, post-randomisation exclusions, and funding were extracted from each trial. Trials were classified as: ITT (reporting the standard intention to treat approach), mITT (reporting a deviation from the standard approach), and no ITT (reporting no approach). Within each meta-analysis, treatment effects were compared between mITT and ITT trials, and between mITT and no ITT trials. The ratio of odds ratios was calculated (value deviated from the intention to treat analysis showed larger intervention effects than trials that reported the standard approach. Where an intention to treat analysis is impossible to perform, authors should clearly report who is included in the analysis and attempt to perform multiple imputations. © Abraha et al 2015.

  14. Design and analysis of group-randomized trials in cancer: A review of current practices.

    Science.gov (United States)

    Murray, David M; Pals, Sherri L; George, Stephanie M; Kuzmichev, Andrey; Lai, Gabriel Y; Lee, Jocelyn A; Myles, Ranell L; Nelson, Shakira M

    2018-06-01

    The purpose of this paper is to summarize current practices for the design and analysis of group-randomized trials involving cancer-related risk factors or outcomes and to offer recommendations to improve future trials. We searched for group-randomized trials involving cancer-related risk factors or outcomes that were published or online in peer-reviewed journals in 2011-15. During 2016-17, in Bethesda MD, we reviewed 123 articles from 76 journals to characterize their design and their methods for sample size estimation and data analysis. Only 66 (53.7%) of the articles reported appropriate methods for sample size estimation. Only 63 (51.2%) reported exclusively appropriate methods for analysis. These findings suggest that many investigators do not adequately attend to the methodological challenges inherent in group-randomized trials. These practices can lead to underpowered studies, to an inflated type 1 error rate, and to inferences that mislead readers. Investigators should work with biostatisticians or other methodologists familiar with these issues. Funders and editors should ensure careful methodological review of applications and manuscripts. Reviewers should ensure that studies are properly planned and analyzed. These steps are needed to improve the rigor and reproducibility of group-randomized trials. The Office of Disease Prevention (ODP) at the National Institutes of Health (NIH) has taken several steps to address these issues. ODP offers an online course on the design and analysis of group-randomized trials. ODP is working to increase the number of methodologists who serve on grant review panels. ODP has developed standard language for the Application Guide and the Review Criteria to draw investigators' attention to these issues. Finally, ODP has created a new Research Methods Resources website to help investigators, reviewers, and NIH staff better understand these issues. Published by Elsevier Inc.

  15. The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan.

    Science.gov (United States)

    Delaney, Anthony P; Peake, Sandra L; Bellomo, Rinaldo; Cameron, Peter; Holdgate, Anna; Howe, Belinda; Higgins, Alisa; Presneill, Jeffrey; Webb, Steve

    2013-09-01

    The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis. In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies. Our statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. We reviewed the data collected by the research team as specified in the study protocol and detailed in the study case report form. We describe information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation, other related therapies and other relevant data with appropriate comparisons between groups. We define the primary, secondary and tertiary outcomes for the study, with description of the planned statistical analyses. We have developed a statistical analysis plan with a trial profile, mock-up tables and figures. We describe a plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies and adverse events. We describe the primary, secondary and tertiary outcomes with identification of subgroups to be analysed. We have developed a statistical analysis plan for the ARISE study, available in the public domain, before the completion of recruitment into the study. This will minimise analytical bias and

  16. Group-sequential analysis may allow for early trial termination

    DEFF Research Database (Denmark)

    Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

    2017-01-01

    BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...... assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis (N = 45) was compared with the group-sequential analysis...... strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. RESULTS: When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis...

  17. A thematic analysis of factors influencing recruitment to maternal and perinatal trials

    Directory of Open Access Journals (Sweden)

    Middleton Philippa F

    2008-08-01

    Full Text Available Abstract Background Recruitment of eligible participants remains one of the biggest challenges to successful completion of randomised controlled trials (RCTs. Only one third of trials recruit on time, often requiring a lengthy extension to the recruitment period. We identified factors influencing recruitment success and potentially effective recruitment strategies. Methods We searched MEDLINE and EMBASE from 1966 to December Week 2, 2006, the Cochrane Library Methodology Register in December 2006, and hand searched reference lists for studies of any design which focused on recruitment to maternal/perinatal trials, or if no studies of maternal or perinatal research could be identified, other areas of healthcare. Studies of nurses' and midwives' attitudes to research were included as none specifically about trials were located. We synthesised the data narratively, using a basic thematic analysis, with themes derived from the literature and after discussion between the authors. Results Around half of the included papers (29/53 were specific to maternal and perinatal healthcare. Only one study was identified which focused on factors for maternal and perinatal clinicians and only seven studies considered recruitment strategies specific to perinatal research. Themes included: participant assessment of risk; recruitment process; participant understanding of research; patient characteristics; clinician attitudes to research and trials; protocol issues; and institutional or organisational issues. While no reliable evidence base for strategies to enhance recruitment was identified in any of the review studies, four maternal/perinatal primary studies suggest that specialised recruitment staff, mass mailings, physician referrals and strategies targeting minority women may increase recruitment. However these findings may only be applicable to the particular trials and settings studied. Conclusion Although factors reported by both participants and clinicians

  18. Ergon-trial: ergonomic evaluation of single-port access versus three-port access video-assisted thoracic surgery.

    Science.gov (United States)

    Bertolaccini, Luca; Viti, Andrea; Terzi, Alberto

    2015-10-01

    Single-port access video-assisted thoracic surgery (VATS), a technique progressively developed from the standard three-port approach in minimally invasive surgery, offers ergonomic advantages but also new challenges for the surgeon. We compared the ergonomics of three-port versus single-port VATS. Posture analysis of surgeons was evaluated during 100 consecutive VATS wedge resections (50 triportal vs. 50 uniportal). Technically demanding procedures (major lung resection) were excluded. Operating table height, monitor height, distance and inclination were adjusted according to operator preference. Body posture was assessed by measuring head-trunk axial rotation and head flexion. Perceived physical strain was self-evaluated on the Borg Category Ratio (CR-10) scale. Mental workload was assessed with the National Aeronautics Space Administration-Task Load indeX (NASA-TLX), a multidimensional tool that rates workloads on six scales (mental, physical and temporal demand; effort; performance; frustration). All procedures were completed without complications. Head-trunk axial rotation was significantly reduced and neck flexion significantly improved in uniportal VATS. Viewing direction significantly declined (p = 0.01), body posture as measured on the Borg CR-10 scale was perceived as more stressful and the NASA-TLX score for overall workload was higher (p = 0.04) during triportal VATS. The NASA-TLX score for frustration was higher with uniportal VATS (p = 0.02), but the score for physical demand was higher in triportal VATS (p = 0.006). The surgeon can maintain a more neutral body posture during uniportal VATS by standing straight and facing the monitor with only minimal neck extension/rotation; however, frustration is greater than with triportal VATS.

  19. Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis

    DEFF Research Database (Denmark)

    Wildt, Signe; Krag, Aleksander; Gluud, Liselotte

    2011-01-01

    Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published...

  20. Statistical analysis plan for the EuroHYP-1 trial

    DEFF Research Database (Denmark)

    Winkel, Per; Bath, Philip M; Gluud, Christian

    2017-01-01

    Score; (4) brain infarct size at 48 +/-24 hours; (5) EQ-5D-5 L score, and (6) WHODAS 2.0 score. Other outcomes are: the primary safety outcome serious adverse events; and the incremental cost-effectiveness, and cost utility ratios. The analysis sets include (1) the intention-to-treat population, and (2...... outcome), logistic regression (binary outcomes), general linear model (continuous outcomes), and the Poisson or negative binomial model (rate outcomes). DISCUSSION: Major adjustments compared with the original statistical analysis plan encompass: (1) adjustment of analyses by nationality; (2) power......) the per protocol population. The sample size is estimated to 800 patients (5% type 1 and 20% type 2 errors). All analyses are adjusted for the protocol-specified stratification variables (nationality of centre), and the minimisation variables. In the analysis, we use ordinal regression (the primary...

  1. Group-sequential analysis may allow for early trial termination

    DEFF Research Database (Denmark)

    Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

    2017-01-01

    BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...

  2. Intra-articular versus intravenous tranexamic acid application in total knee arthroplasty: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mi, Bobin; Liu, Guohui; Zhou, Wu; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

    2017-07-01

    The purpose of this meta-analysis was to compare the blood loss and complications of intra-articular (IA) with intravenous (IV) tranexamic acid (TXA) for total knee arthroplasty (TKA). A comprehensive search of studies was conducted to identify related articles in Pubmed, Embase, Cochrane central Register of Controlled Trials, springerLink, OVID and the Research published from January 1980 to September 2016. All studies that compared IA TXA with IV TXA application on TKA were included. Main outcomes of the two methods were collected and analyzed by using Review Manager 5.3. There were 16 randomized controlled trials with 1308 cases met the criteria. Compared with IV TXA, IA TXA had similar blood volume of drainage, hidden blood loss, transfusion rate and complications (P > 0.05). IA TXA had lower total blood loss than IV TXA, and there was significant difference (P  0.05) when compared with IA TXA. Both IA TXA and single dose of IV TXA are effective in reducing total blood loss and postoperative hemoglobin drop without increasing complications of DVT or PE. The current meta-analysis suggests that 1.5 g TXA by IA administration or 1 g TXA by IV administration 10 min before tourniquet deflation is effective and safe in patients undergoing TKA.

  3. Potassium supplementation and heart rate : A meta-analysis of randomized controlled trials

    NARCIS (Netherlands)

    Gijsbers, L.; Moelenberg, F. J. M.; Bakker, S. J. L.; Geleijnse, J. M.

    Background and aims: Increasing the intake of potassium has been shown to lower blood pressure, but whether it also affects heart rate (HR) is largely unknown. We therefore assessed the effect of potassium supplementation on HR in a meta-analysis of randomized controlled trials. Methods and results:

  4. Training Head Start Teachers to Conduct Trial-Based Functional Analysis of Challenging Behavior

    Science.gov (United States)

    Rispoli, Mandy; Burke, Mack D.; Hatton, Heather; Ninci, Jennifer; Zaini, Samar; Sanchez, Lisa

    2015-01-01

    Trial-based functional analysis (TBFA) is a procedure for experimentally identifying the function of challenging behavior within applied settings. The purpose of this study was to examine the effects of a TBFA teacher-training package in the context of two Head Start centers implementing programwide positive behavior support (PWPBS). Four Head…

  5. Trial-Based Functional Analysis and Functional Communication Training in an Early Childhood Setting

    Science.gov (United States)

    Lambert, Joseph M.; Bloom, Sarah E.; Irvin, Jennifer

    2012-01-01

    Problem behavior is common in early childhood special education classrooms. Functional communication training (FCT; Carr & Durand, 1985) may reduce problem behavior but requires identification of its function. The trial-based functional analysis (FA) is a method that can be used to identify problem behavior function in schools. We conducted…

  6. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.

    LENUS (Irish Health Repository)

    Sattar, Naveed

    2010-02-27

    Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.

  7. A simple sample size formula for analysis of covariance in cluster randomized trials.

    NARCIS (Netherlands)

    Teerenstra, S.; Eldridge, S.; Graff, M.J.; Hoop, E. de; Borm, G.F.

    2012-01-01

    For cluster randomized trials with a continuous outcome, the sample size is often calculated as if an analysis of the outcomes at the end of the treatment period (follow-up scores) would be performed. However, often a baseline measurement of the outcome is available or feasible to obtain. An

  8. The effects of multi-domain versus single-domain cognitive training in non-demented older people: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Cheng Yan

    2012-03-01

    Full Text Available Abstract Background Whether healthy older people can benefit from cognitive training (CogTr remains controversial. This study explored the benefits of CogTr in community dwelling, healthy, older adults and compared the effects of single-domain with multi-domain CogTr interventions. Methods A randomized, controlled, 3-month <