Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
A class of potent, nonsteroidal, selective indazole ether-based glucocorticoid receptor modulators (SGRMs) was developed for the inhaled treatment of respiratory diseases. Starting from an orally available compound with demonstrated anti-inflammatory activity in rat, a soft-drug strategy was implemented to ensure rapid elimination of drug candidates to minimize systemic GR activation. The first clinical candidate 1b (AZD5423) displayed a potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate, 15m (AZD7594), that demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, indicating potential for once-daily treatment.
Adolescents with undiagnosed exercise-induced dyspnea have respiratory symptoms and are affected in daily life but have the same level of physical activity as adolescents without exercise-induced respiratory symptoms.
Objectives
To study the prevalence of exercise‐induced bronchoconstriction (EIB) and exercise‐induced laryngeal obstruction (EILO) in adolescent athletes.
Methods
All adolescents (n = 549) attending first year at a sports high school in 2016 and 2017, were invited to answer a questionnaire on respiratory symptoms. The 367 responding participants were divided into two groups based on whether they reported exercise‐induced dyspnea (dyspnea group) or not (nondyspnea group). Randomly selected participants in each group were invited to undergo two standardized exercise tests, an EIB test and a continuous laryngoscopy exercise (CLE) test, to investigate EILO.
Results
In total, 98 participants completed an EIB test, 75 of whom also completed a CLE test. Positive EIB tests: eight of 41 in the dyspnea group and 16 of 57 in the nondyspnea group. Positive CLE tests: 5 of 34 in the dyspnea group and three of 41 in the nondyspnea group. The estimated prevalence of EIB was 23.1% (95% confidence interval [CI]: 14.5–33.8) and of EILO 8.1% (95% CI: 2.5–18.5) in the whole study population. No differences in prevalence of EIB or EILO were found between the dyspnea and the nondyspnea groups.
Conclusion
EIB was highly prevalent in this cohort of adolescent athletes. EILO was less prevalent, but represents an important differential diagnosis to EIB. Self‐reported exercise‐induced dyspnea is a weak indicator for both EIB and EILO and standardized testing should be provided.
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