Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas.

Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy. SIGNIFICANCE: True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.

Can Synchronous Online Near-Peer Teaching Offer the Same Benefits as the Face-to-Face Version When Used in Clinical Neuroanatomy Education?

COVID-19 sparked massive educational change and dictated that traditional courses rapidly transitioned online. This presented a unique challenge for anatomy, a visually orientated subject that has conventionally relied heavily on face-to-face teaching. Near-peer teaching (NPT) is one method with the potential to address this challenge. When given more responsibility, student-teachers are more likely to deliver effective teaching sessions and include the most appropriate resources for the learners. Current literature surrounding the use of NPT in both frontline and supplementary settings have already demonstrated its potential, however, its efficacy in an online environment is still largely unknown. The Faculty of Medicine at the University of Southampton has a well-established NPT programme as part of its 5 year undergraduate course (BM5). A quasi-experimental cohort study was conducted to determine whether the benefits associated with NPT are preserved when delivered online. Two cohorts of second year BM5 students received cranial nerve NPT as part of their formal clinical neuroanatomy module, one face to face (N = 150) and the other online (N = 168). Knowledge tests were undertaken by participants to assess knowledge gain and retention, and an established Likert style survey instrument was administered to assess student perceptions. Both online and face-to-face NPT sessions resulted in significant increases in student knowledge gain (p < 0.0001), yet the difference between the two was insignificant (p = 0.2432). Subsequent knowledge retention tests were also shown to be similar (p = 0.7732). Students perceived both methods of NPT delivery positively but found online NPT less enjoyable (p < 0.0001) and considered it to be a more inefficient use of time (p = 0.0035). This research suggests that online NPT can be deployed without a detrimental risk to learning when compared to traditional NPT applications in pre-clinical neuroanatomy teaching.

Unusual complication of late presentation deceleration aortic injury.

A 50-year-old patient presented with a stroke. An ascending aortic mass noted by computed tomography was attached to the aortic wall and was found to be thrombus at surgery. Pathologic examination revealed an intraluminal thrombus attached to a focal segment of intimal fragmentation. Sectioning of the aortic wall revealed what were findings consistent with what would be noted with a previously unrecognized traumatic ascending aortic deceleration injury. To our knowledge, this is the first case of a late presentation of deceleration aortic injury, presenting with a thrombus within the ascending aorta.

A hybrid approach to identifying and assessing interactions between climate action (SDG13) policies and a range of SDGs in a UK context.

In 2015 the United Nations drafted the Paris Agreement and established the Sustainable Development Goals (SDGs) for all nations. A question of increasing relevance is the extent to which the pursuit of climate action (SDG 13) interacts both positively and negatively with other SDGs. We tackle this question through a two-pronged approach: a novel, automated keyword search to identify linkages between SDGs and UK climate-relevant policies; and a detailed expert survey to evaluate these linkages through specific examples. We consider a particular subset of SDGs relating to health, economic growth, affordable and clean energy and sustainable cities and communities. Overall, we find that of the 89 UK climate-relevant policies assessed, most are particularly interlinked with the delivery of SDG 7 (Affordable and Clean Energy) and SDG 11 (Sustainable Cities and Communities) and that certain UK policies, like the Industrial Strategy and 25-Year Environment Plan, interlink with a wide range of SDGs. Focusing on these climate-relevant policies is therefore likely to deliver a wide range of synergies across SDGs 3 (Good Health and Well-being), 7, 8 (Decent Work and Economic Growth), 9 (Industry, Innovation and Infrastructure), 11, 14 (Life Below Water) and 15 (Life on Land). The expert survey demonstrates that in addition to the range of mostly synergistic interlinkages identified in the keyword search, there are also important potential trade-offs to consider. Our analysis provides an important new toolkit for the research and policy communities to consider interactions between SDGs, which can be employed across a range of national and international contexts. Supplementary Information: The online version contains supplementary material available at 10.1007/s43621-021-00051-w.

Motion of the lips of brass players during extremely loud playing.

When a brass instrument is played loudly, the energy level of the higher harmonics increases dramatically. The generally accepted explanation for this is non-linear steepening of the wavefront and generation of shock waves within the instrument bore. However, it has also been suggested that changes in the player's lip vibration could play a role in generating this "brassy" sound. To test this hypothesis, the dependence of lip opening-area on time has been measured for different dynamic levels in trombones and horns. Results suggest that the behavior of the open area does not change dramatically when the instrument enters the brassy regime.