BRAF mutation testing with a rapid,fully integrated molecular diagnostics system

Fast and accurate diagnostic systems are needed for further implementation of precision therapy of BRAF-mutant and other cancers. The novel Idylla^TM BRAF Mutation Test has high sensitivity and shorter turnaround times compared to other methods. We used Idylla to detect BRAF V600 mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples and compared these results with those obtained using the cobas 4800 BRAF V600 Mutation Test or MiSeq deep sequencing system and with those obtained by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory employing polymerase chain reaction–based sequencing, mass spectrometric detection, or next-generation sequencing. In one set of 60 FFPE tumor samples (15 with BRAF mutations per Idylla), the Idylla and cobas results had an agreement of 97%. Idylla detected BRAF V600 mutations in two additional samples. The Idylla and MiSeq results had 100% concordance. In a separate set of 100 FFPE tumor samples (64 with BRAF mutation per Idylla), the Idylla and CLIA-certified laboratory results demonstrated an agreement of 96% even though the tests were not performed simultaneously and different FFPE blocks had to be used for 9 cases. The Idylla^TM BRAF Mutation Test produced results quickly (sample to results time was about 90 minutes with about 2 minutes of hands on time) and the closed nature of the cartridge eliminates the risk of PCR contamination. In conclusion, our observations demonstrate that the Idylla test is rapid and has high concordance with other routinely used but more complex BRAF mutation–detecting tests.     

Impact of teleconsultation on visual and refractive outcomes in patients undergoing laser refractive surgery during COVID-19

Purpose:To assess the role of remote teleconsultation (TC) follow-up care following a successful and uneventful laser vision correction.Methods:The study is a retrospective, comparative analysis of patients undergoing laser vision correction at tertiary care eye hospital in Southern India. The patients were divided into two groups. The first group included patients operated on before the coronavirus disease (COVID-19) pandemic and were followed up with physical consultations during their follow-up visit (Group 1). The second group comprised patients operated on during the pandemic and had at least one remote TC during their post-operative follow-up (Group 2).Results:A total of 1088 eyes of 564 patients and 717 eyes of 372 patients were included in Group 1 and 2, respectively. The mean number of visits for the patients from Group 2 during the COVID period (2.56 +/- 0.74 days) was significantly lesser (P < 0.0001) than that of Group 1 in the pre-COVID period (3.53 +/- 1.07 days). Close to 90% of the eyes achieved an uncorrected distance visual acuity (UDVA) of 20/20 in both groups (P = 0.925). 96.50% of the eyes in Group 1 and 98.18% of the eyes in Group 2 achieved UCVA 20/25 or better (P = 0.049). Eight eyes (0.73%) in Group 1 and one eye (0.14%) in Group 2 reported a loss of 2 or more lines. However, the results were not statistically significant (P = 0.156). None of the groups had any patients who had a sight-threatening complication.Conclusion:Remote TC following refractive surgery is safe and can be effectively integrated into routine refractive practice to reduce travel to the hospital for a physical consult.     

Apprehending the NAD+–ADPr-Dependent Systems in the Virus World

NAD⁺ and ADP-ribose (ADPr)-containing molecules are at the interface of virus–host conflicts across life encompassing RNA processing, restriction, lysogeny/dormancy and functional hijacking. We objectively defined the central components of the NAD⁺–ADPr networks involved in these conflicts and systematically surveyed 21,191 completely sequenced viral proteomes representative of all publicly available branches of the viral world to reconstruct a comprehensive picture of the viral NAD⁺–ADPr systems. These systems have been widely and repeatedly exploited by positive-strand RNA and DNA viruses, especially those with larger genomes and more intricate life-history strategies. We present evidence that ADP-ribosyltransferases (ARTs), ADPr-targeting Macro, NADAR and Nudix proteins are frequently packaged into virions, particularly in phages with contractile tails (Myoviruses), and deployed during infection to modify host macromolecules and counter NAD⁺-derived signals involved in viral restriction. Genes encoding NAD⁺–ADPr-utilizing domains were repeatedly exchanged between distantly related viruses, hosts and endo-parasites/symbionts, suggesting selection for them across the virus world. Contextual analysis indicates that the bacteriophage versions of ADPr-targeting domains are more likely to counter soluble ADPr derivatives, while the eukaryotic RNA viral versions might prefer macromolecular ADPr adducts. Finally, we also use comparative genomics to predict host systems involved in countering viral ADP ribosylation of host molecules.     

Influence of intensive lipid‐lowering on CT derived fractional flow reserve in patients with stable chest pain: Rationale and design of the FLOWPROMOTE study

IntroductionCoronary CT angiography (CTA) derived fractional flow reserve (FFR_CT) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated.AimTo test whether lipid lowering therapy is associated with significant improvement in FFR_CT, and whether there is a dose–response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery.MethodsInvestigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first‐line CTA, and FFR_CT ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFR_CT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18‐month difference in FFR_CT using (1) the FFR_CT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study.ConclusionThe results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease.     

Experimental Tests and Numerical Simulations on the Ballistic Impact Response of a Highly Inhomogeneous Aluminium Foam

A sandwich structure is a composite material consisting of thin skins encapsulating a cellular core. Such structures have proven to be excellent energy absorbents and are frequently found in various types of protection. Even so, few studies exist in the open literature on the response of the core material itself under extreme loadings such as blast and impact. Since a blast load is usually accompanied by numerous fragments, it is important to understand and be able to predict the ballistic impact resistance of the often highly inhomogeneous cellular core materials in design. In this study, the ballistic impact response of an aluminium foam with a complex cell structure has been investigated both experimentally and numerically. First, an extensive material test program involving compression tests on cubic specimens loaded in the thickness direction of the foam was carried out to reveal the mechanical properties of the material. In addition, several of the specimens were scanned before testing using X-ray Micro Computed Tomography (XRMCT) to map the multi-scale topology and morphology of the material. These data were later analysed to extract density-variation plots in many different material orientations. Second, ballistic impact tests were conducted using a gas gun where rigid spheres were launched towards aluminium foam plates, and the ballistic limit velocity and curve of the foam material were established. Finally, numerical simulations of both the material tests and the ballistic impact tests were carried out using LS-DYNA and different modelling approaches based on the XRMCT data. It will be shown that, independent of the modelling strategy applied, good agreement between the experimental impact tests and the numerical predictions can be obtained. However, XRMCT data are important if the final goal is to numerically optimise and improve the behaviour of inhomogeneous foams with respect to energy absorption, thermal isolation, or similar properties.