Methylation-based algorithms for diagnosis: experience from neuro-oncology

Brain tumours are the most common tumour‐related cause of death in young people. Survivors are at risk of significant disability, at least in part related to the effects of treatment. Therefore, there is a need for a precise diagnosis that stratifies patients for the most suitable treatment, matched to the underlying biology of their tumour. Although traditional histopathology has been accurate in predicting treatment responses in many cases, molecular profiling has revealed a remarkable, previously unappreciated, level of biological complexity in the classification of these tumours. Among different molecular technologies, DNA methylation profiling has had the most pronounced impact on brain tumour classification. Furthermore, using machine learning‐based algorithms, DNA methylation profiling is changing diagnostic practice. This can be regarded as an exemplar for how molecular pathology can influence diagnostic practice and illustrates some of the unanticipated benefits and risks. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Resistance training volume load with and without exercise displacement

Monitoring the resistance training volume load (VL) (sets × reps × load) is essential to managing resistance training and the recovery⁻adaptation process. Eight trained weightlifters, seven of which were at national level, participated in the study. VL was measured both with (VLwD) and without (VL) the inclusion of barbell displacement, across twenty weeks of training, in order to allow for comparisons to be made of these VL calculating methods. This consisted of recording the load, repetition count, and barbell displacement for every set executed. Comparisons were made between VL and VLwD for individual blocks of training, select training weeks, and select training days. Strong, statistically significant correlations (r ≥ 0.78, < 0.001) were observed between VL and VLwD between all training periods analyzed. -tests revealed statistically significant ( ≤ 0.018) differences between VL and VLwD in four of the seven training periods analyzed. The very strong relationship between VL and VLwD suggest that a coach with time constraints and a large number of athletes can potentially spare the addition of displacement. However, differences in percent change indicate that coaches with ample time should include displacement in VL calculations, in an effort to acquire more precise workload totals

Direct mapping of surface plasmon dispersion using imaging scatterometry

© 2013 American Institute of PhysicsThe iso-frequency contours of diffracted surface plasmons on metallic bigratings have been directly recorded using imaging scatterometry. Metallic rectangular bigratings, formed of two “crossed” surface relief gratings, are used to demonstrate this measurement technique. By deepening one of the constituent gratings, control of the surface plasmon dispersion anisotropy is shown in the recorded iso-frequency maps. Collating the iso-frequency contours over a range of wavelengths from 500 nm to 700 nm leads to a three-dimensional map of the surface plasmon dispersion

Normalization of early isometric force production as a percentage of peak force during multijoint isometric assessment

Purpose: To determine the reliability of early force production (50-, 100-, 150-, 200-, 250 ms) relative to peak force (PF) during an isometric mid-thigh pull (IMTP) and assess the relationships between these variables. Methods: Male collegiate athletes (n = 29; age: 21.1 ± 2.9 years; height: 1.71 ± 0.07 m; body mass: 71.3 ± 13.6 kg) performed IMTPs during two separate testing sessions. Net PF and net force produced at each epoch were calculated. Within- and between-session reliability were determined by using intraclass correlation coefficients (ICC) and coefficient of variation (CV%). Additionally, Pearson’s correlation coefficients and coefficient of determination, were calculated to examine the relationships between PF and time-specific force production. Results: Net PF and time-specific force demonstrated very high to almost perfect reliability both within- and between-sessions (ICCs 0.82-0.97; CV% 0.35-1.23%). Similarly, time-specific force expressed as a percentage of PF demonstrated very high to almost perfect reliability both within- and between-sessions (ICCs 0.76-0.86; CV% 0.32-2.51%). Strong to nearly perfect relationships (r = 0.615-0.881) exist between net PF and time-specific net force, with relationships improving over longer epochs. Conclusion: Based on the smallest detectable difference, a change in force at 50 ms expressed relative to PF >10% and early force production (100-, 150-, 200- and 250 ms) expressed relative to PF of >2% should be considered meaningful. Expressing early force production as a percentage of PF is reliable and may provide greater insight into the adaptations to the previous training phase than PF alone

Village Water Ozonation System

The Village Water Ozonation System (VWOS) team’s core mission statement is to provide economically sustainable and culturally sensitive drinking water solutions for communities, to empower communities with the ability to properly maintain their drinking water supply, and to transform people’s lives by decreasing the occurrences of waterborne diseases. Currently, the VWOS team is partnering with Friends in Action to design and implement two drinking water treatment systems for the community living on Rama Cay, an island in the Bluefields Lagoon on the eastern coastline of Nicaragua. The wells on the island are contaminated with E. coli and other bacteria and contain high levels of salt that cause the water to be unhealthy, distasteful, and corrosive to metal equipment in the system. The team hopes to design a system that will disinfect the water, remove salinity from the well water with a safe and efficient disposal of all byproducts, and decrease corrosion agents. VWOS is partnering with Forward Edge International for the third time (Nicaragua 2009 and Mexico 2016) to design water treatment systems for communities in Oaxaca, Mexico and Kijabe, Kenya. The system for Oaxaca is ready for implementation and awaits availability to travel. The system for Kijabe is in the initial stage of communicating with the client on specifics for the design.https://mosaic.messiah.edu/engr2021/1018/thumbnail.jp

The impact of Stieltjes' work on continued fractions and orthogonal polynomials

Stieltjes' work on continued fractions and the orthogonal polynomials related to continued fraction expansions is summarized and an attempt is made to describe the influence of Stieltjes' ideas and work in research done after his death, with an emphasis on the theory of orthogonal polynomials

The DNA methylome of human sperm is distinct from blood with little evidence for tissue-consistent obesity associations

Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in spermatozoa. We profiled genome-wide DNA methylation using the Illumina MethylationEPIC array in a cross-sectional study of matched human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) males to analyse tissue covariation of DNA methylation, and identify obesity-associated methylomic signatures. We found that DNA methylation signatures of human blood and spermatozoa are highly discordant, and methylation levels are correlated at only a minority of CpG sites (~1%). At the majority of these sites, DNA methylation appears to be influenced by genetic variation. Obesity-associated DNA methylation in blood was not generally reflected in spermatozoa, and obesity was not associated with altered covariation patterns or accelerated epigenetic ageing in the two tissues. However, one cross-tissue obesity-specific hypermethylated site (cg19357369; chr4:2429884; P = 8.95 × 10^{-8}; 2% DNA methylation difference) was identified, warranting replication and further investigation. When compared to a wide range of human somatic tissue samples (n = 5,917), spermatozoa displayed differential DNA methylation across pathways enriched in transcriptional regulation. Overall, human sperm displays a unique DNA methylation profile that is highly discordant to, and practically uncorrelated with, that of matched peripheral blood. We observed that obesity was only nominally associated with differential DNA methylation in sperm, and therefore suggest that spermatozoal DNA methylation is an unlikely mediator of intergenerational effects of metabolic traits

Molecular characteristics of long-term epilepsy-associated tumours (LEATs) and mechanisms for tumour-related epilepsy (TRE)

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour-related epilepsy has a profound impact on patients with brain tumours and these seizures are often refractory to anti-epileptic treatments, resulting in long-term disability and patient morbidity. Despite the drastic impact epilepsy-associated tumours have on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards furthering our understanding of the molecular and developmental backgrounds of specific epilepsy associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of tumour-related epilepsy. In this review, we aim to summarise the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy-associated tumours. This article is protected by copyright. All rights reserved

Improving the measurement and acoustic performance of transparent face masks and shields

Opaque face masks harm communication by preventing speech-reading (lip-reading) and attenuating high-frequency sound. Although transparent masks and shields (visors) with clear plastic inserts allow speech-reading, they usually create more sound attenuation than opaque masks. Consequently, an iterative process was undertaken to create a better design, and the instructions to make it are published. The experiments showed that lowering the mass of the plastic inserts decreases the high-frequency sound attenuation. A shield with a clear thermoplastic polyurethane (TPU) panel had an insertion loss of (2.0 ± 1.1) dB for 1.25–8 kHz, which improves on previous designs that had attenuations of 11.9 dB and above. A cloth mask with a TPU insert was designed and had an insertion loss of (4.6 ± 2.3) dB for 2–8 kHz, which is better than the 9–22 dB reported previously in the literature. The speech intelligibility index was also evaluated. Investigations to improve measurement protocols that use either mannikins or human talkers were undertaken. Manufacturing variability and inconsistency of human speaking were greater sources of experimental error than fitting differences. It was shown that measurements from a mannikin could match those from humans if insertion losses from four human talkers were averaged