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However, use of ensemble averaging method with a large number of SEP trials may minimize time-variant abnormalities of conductivity [15]. To obtain a reliable estimation of single evoked potential response, several methods have been developed under poor signal-to-noise ratio [13, 19--21]. In 1979, Kearney proposed to use Weiner filtering to the estimate tonic electromyography activity responses after electrical stimulation of the foot [22]. Results showed a significant reduction in the number of averaging, but it did not prove the usefulness in single trial SEP extraction. It is much more difficult to extract single-trial SEP than other evoked potentials like evoked electromyography, visual evoked potentials and audio evoked potentials. Recently, improved performance has been reported for blind source separation, which is a technique that recovers unknown source signals from mixed and observed data sets [13, 19, 20]. Compared with other blind identification algorithms for SEP detection, second-order blind identification has many advantages such as simplicity, reliability, robustness, and applicable Gaussian signals [13, 19, 20]. More importantly, second-order blind identification is robust for short serial-signals [23]. Therefore, second-order blind identification offers a favorable alternative for detecting neural transmission variation [13].


Single trial SEP measured using second order blind identification with a reference in CSM patients. The 50 single trial SEP are presented with latency and amplitude values. The above is the three dimensional map of single-trial SEP in latency-amplitude-trial number, and the below is the projection on latency-trial number coordinate. The color presents the values of single-trial SEP amplitude with a latency between 10 ms to 20 ms




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The following steps were taken to find out if a study had been registered. First, the full text of the included articles was checked for a trial registration number. When this number was not reported, the corresponding author was asked through email whether the study had been registered and, if so, in which registry and under which registration number. Contact attempts were limited to three emails, each sent in a week's gap. If no answer was received, the WHO Search Portal, which searches several registries, was used. In addition, we searched ClinicalTrials.gov, the International Standard Randomised Controlled Trial Number Register and national trial registers of the country of the first author. In these registries, we searched for the names of first, last and corresponding authors, publication title, evaluated tests and target disease/outcome. We matched registered records with publications by comparing the data on study design, sample size, country, outcomes and contact information. If no registration number was found, a study was considered as not registered. When a paper included in our review was a secondary (post hoc) analysis, we also considered the study as registered if we were able to identify a registered record for the initial study, in which the data had been collected. We categorised studies as those where the data collection had and had not been registered. We further classified studies with a registered data collection as those that had registered the published primary outcomes, those that had registered the published primary aim but vaguer or slightly different, and those that had not registered the primary outcomes or aims.


The search identified 1941 articles of which 351 fulfilled the inclusion criteria (figure 1). Characteristics of included studies are summarised in table 1. The majority of studies (71%) evaluated the accuracy of a diagnostic test, while 29% evaluated a prognostic test. Comparable numbers of studies focused on imaging tests and tests based on a laboratory technique: 33% and 36%, respectively. The remainder focused on another type of test (24%), such as physical examination, electrocardiography (ECG) or pathology, or on (a combination of) tests that were assigned to more than one category (8%). Some form of industry involvement was reported by 19% of the included studies, while 58% reported sources of funding that did not include an industrial party. The remainder (23%) did not have or report an (external) source of funding. 2ff7e9595c


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