Three biomarker tests to help diagnose preterm labour: a systematic review and economic evaluation

Background: Preterm birth may result in short- and long-term health problems for the child. Accurate diagnoses of preterm births could prevent unnecessary (or ensure appropriate) admissions into hospitals or transfers to specialist units. Objectives: The purpose of this report is to assess the test accuracy, clinical effectiveness and cost-effectiveness of the diagnostic tests PartoSure™ (Parsagen Diagnostics Inc., Boston, MA, USA), Actim® Partus (Medix Biochemica, Espoo, Finland) and the Rapid Fetal Fibronectin (fFN)® 10Q Cassette Kit (Hologic, Inc., Marlborough, MA, USA) at thresholds ≠50 ng/ml [quantitative fFN (qfFN)] for women presenting with signs and symptoms of preterm labour relative to fFN at 50 ng/ml. Methods: Systematic reviews of the published literature were conducted for diagnostic test accuracy (DTA) studies of PartoSure, Actim Partus and qfFN for predicting preterm birth, the clinical effectiveness following treatment decisions informed by test results and economic evaluations of the tests. A model-based economic evaluation was also conducted to extrapolate long-term outcomes from the results of the diagnostic tests. The model followed the structure of the model that informed the 2015 National Institute for Health and Care Excellence guidelines on preterm labour diagnosis and treatment, but with antenatal steroids use, as opposed to tocolysis, driving health outcomes. Results: Twenty studies were identified evaluating DTA against the reference standard of delivery within 7 days and seven studies were identified evaluating DTA against the reference standard of delivery within 48 hours. Two studies assessed two of the index tests within the same population. One study demonstrated that depending on the threshold used, qfFN was more or less accurate than Actim Partus, whereas the other indicated little difference between PartoSure and Actim Partus. No study assessing qfFN and PartoSure in the same population was identified. The test accuracy results from the other included studies revealed a high level of uncertainty, primarily attributable to substantial methodological, clinical and statistical heterogeneity between studies. No study compared all three tests simultaneously. No clinical effectiveness studies evaluating any of the three biomarker tests were identified. One partial economic evaluation was identified for predicting preterm birth. It assessed the number needed to treat to prevent a respiratory distress syndrome case with a ‘treat-all’ strategy, relative to testing with qualitative fFN. Because of the lack of data, our de novo model involved the assumption that management of pregnant women fully adhered to the results of the tests. In the base-case analysis for a woman at 30 weeks’ gestation, Actim Partus had lower health-care costs and fewer quality-adjusted life-years (QALYs) than qfFN at 50 ng/ml, reducing costs at a rate of £56,030 per QALY lost compared with qfFN at 50 ng/ml. PartoSure is less costly than Actim Partus while being equally effective, but this is based on diagnostic accuracy data from a small study. Treatment with qfFN at 200 ng/ml and 500 ng/ml resulted in lower cost savings per QALY lost relative to fFN at 50 ng/ml than treatment with Actim Partus. In contrast, qfFN at 10 ng/ml increased QALYs, by 0.002, and had a cost per QALY gained of £140,267 relative to fFN at 50 ng/ml. Similar qualitative results were obtained for women presenting at different gestational ages. Conclusion: There is a high degree of uncertainty surrounding the test accuracy and cost-effectiveness results. We are aware of four ongoing UK trials, two of which plan to enrol > 1000 participants. The results of these trials may significantly alter the findings presented here. Study registration: The study is registered as PROSPERO CRD42017072696. Funding: The National Institute for Health Research Health Technology Assessment programme

A co-registration investigation of inter-word spacing and parafoveal preview: Eye movements and fixation-related potentials

Participants’ eye movements (EMs) and EEG signal were simultaneously recorded to examine foveal and parafoveal processing during sentence reading. All the words in the sentence were manipulated for inter-word spacing (intact spaces vs. spaces replaced by a random letter) and parafoveal preview (identical preview vs. random letter string preview). We observed disruption for unspaced text and invalid preview conditions in both EMs and fixation-related potentials (FRPs). Unspaced and invalid preview conditions received longer reading times than spaced and valid preview conditions. In addition, the FRP data showed that unspaced previews disrupted reading in earlier time windows of analysis, compared to string preview conditions. Moreover, the effect of parafoveal preview was greater for spaced relative to unspaced conditions, in both EMs and FRPs. These findings replicate well-established preview effects, provide novel insight into the neural correlates of reading with and without inter-word spacing and suggest that spatial selection precedes lexical processing

Evaluating Effects of Divided Hemispheric Processing on Word Recognition in Foveal and Extrafoveal Displays: The Evidence from Arabic

Background: Previous studies have claimed that a precise split at the vertical midline of each fovea causes all words to the left and right of fixation to project to the opposite, contralateral hemisphere, and this division in hemispheric processing has considerable consequences for foveal word recognition. However, research in this area is dominated by the use of stimuli from Latinate languages, which may induce specific effects on performance. Consequently, we report two experiments using stimuli from a fundamentally different, non-Latinate language (Arabic) that offers an alternative way of revealing effects of split-foveal processing, if they exist. Methods and Findings: Words (and pseudowords) were presented to the left or right of fixation, either close to fixation and entirely within foveal vision, or further from fixation and entirely within extrafoveal vision. Fixation location and stimulus presentations were carefully controlled using an eye-tracker linked to a fixation-contingent display. To assess word recognition, Experiment 1 used the Reicher-Wheeler task and Experiment 2 used the lexical decision task. Results: Performance in both experiments indicated a functional division in hemispheric processing for words in extrafoveal locations (in recognition accuracy in Experiment 1 and in reaction times and error rates in Experiment 2) but no such division for words in foveal locations. Conclusions: These findings from a non-Latinate language provide new evidence that although a functional division i

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

Investigating the use of world knowledge during on-line comprehension in adults with autism spectrum disorder

The on-line use of world knowledge during reading was examined in adults with autism spectrum disorder (ASD). Both ASD and typically developed (TD) adults read sentences that included plausible, implausible and anomalous thematic relations, as their eye movements were monitored. No group differences in the speed of detection of the anomalous violations were found, but the ASD group showed a delay in detection of implausible thematic relations. These findings suggest that there are subtle differences in the speed of world knowledge processing during reading in ASD

Time on Task Effects during Interactive Visual Search

There is a major shift taking place in airports across the globe, changing from 2D dual-view X-ray screening to 3D CT screening. 3D CT screening is believed to improve target detection since it enables screeners to interact with images of passenger baggage (i.e., rotating and zooming into the displays). The change in screening technology is moving what was once a purely visual search task to an interactive search task. Here, we conducted two experiments with a large sample size during February of 2023 (695 participants) to examine (1) changes in search performance between a simulated dual-view and simulated interactive search task and (2) the effects of time on task upon performance. Consistent with past research, we found that interactive search, when compared with dual-view search, produced higher response accuracy rates coupled with increased reaction times. However, while we found effects of time on task (RTs reduced, and participants became more likely to respond ‘absent’ as the experiments progressed) there was no evidence that these effects differed across simulated dual-view and simulated interactive searches. The results are discussed in relation to benefits of interactive search for supporting target detection by airport screeners

Lysyl oxidase and adipose tissue dysfunction

Lysyl oxidase (LOX) is an enzyme crucial for collagen fibre crosslinking and thus for fibrosis development. Fibrosis is characterised by a surplus of collagen fibre accumulation and is amongst others also a feature of obesity-associated dysfunctional adipose tissue (AT) which has been linked with type 2 diabetes. We hypothesised that in type 2 diabetes and obesity LOX expression and activity will be increased as a consequence of worsening AT dysfunction. This study aimed to provide a comprehensive characterisation of LOX in human AT