Peripheral Nerve Tumors in Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis

Neurofibromatosis was first described in the nineteenth century. At the time, Friederich Daniel Von Recklinghausen detailed two cases of multiple neurofibromas. Although reports of similar cases had been published before his, Von Recklinghausen is credited with the initial description in 1882, postulating that the tumors originated from nerve sheath and plexal connective tissue. Similarly, in 1822 John Henry Wishart described what is believed to be neurofibromatosis type 2; however, it was Harvey Cushing’s description of a case of bilateral vestibular schwannomas in 1916 that highlighted and increased awareness of the disease (albeit the original presentation was thought to be in the context of neurofibromatosis type 1). Since their original description, understanding of these neurocutaneous diseases has greatly expanded. Knowledge of the genotypic mutations and molecular mechanisms underlying the disease pathophysiology has resulted in natural history enlightenment and optimal treatment refinement. However, many aspects of neurofibromatosis have yet to be explained and remain active areas of investigation. In this chapter, clinical, radiological, and surgical considerations for peripheral nerve tumor management in the context of neurocutaneous disorders are reviewed. More specifically, clinical presentations, pathological and imaging findings, as well as management for neurofibromatosis type 1, type 2, and schwannomatosis are comprehensively discussed

Investigating the contribution of extended radio sources to the Epoch of Reionization power spectrum

We investigate the contribution of extended radio sources such as Centaurus A, and Galactic supernova remnants (SNRs) to our ability to detect the statistical 21-cm signal from the Epoch of Reionisation (EoR) with the Murchison Widefield Array (MWA). These sources are typically ignored because they are in highly attenuated parts of the MWA primary beam, however, in aggregate, these sources have apparent flux densities of 10, Jy on angular scales we expect to detect the 21-cm signal. We create bespoke multicomponent 2D Gaussian models for Galactic SNRs and for Centaurus A, and simulate the visibilities for two MWA snapshot observations. We grid those visibilities and then Fourier transform them with respect to frequency, averaging them both spherically and cylindrically to produce the 1D and 2D power spectra. We compare the simulated 1D power spectra to the expected 21-$\rm {cm}$ power spectrum. We find that although these extended sources are in highly attenuated parts of the MWA primary beam pattern, collectively they have enough power (∼104-105 m mK2 it h-3, Mpc3) on EoR significant modes (| k| ≲ 0.1\, h\,\rm Mpc-1) to prohibit detection of the 21-rm cm signal (∼104 rm mK2\, ⁢ h-3,\rm Mpc3). We find that 50-90 per cent of sources must be removed in order to reduce leakage to a level of ∼ 10-20 per cent of the 21-rm cm power spectrum on EoR significant modes. The effects of wide-field extended sources will have implications on the detectability of the 21-rm cm signal for the MWA and with the future Square Kilometre Array (SKA)

Radiological data of brachial plexus avulsion injury associated spinal cord herniation (BPAI-SCH) and comparison to anterior thoracic spinal cord herniation (ATSCH).

Spinal cord herniation (SCH) is a rare cause of myelopathy. When reported, SCH has most commonly been described as occurring spontaneously in the thoracic spine, and being idiopathic in nature (anterior thoracic spinal cord herniation, ATSCH) [1-3]. Several theories have been proposed to explain its occurrence, including congenital, inflammatory, and traumatic etiologies alike [1-4]. Even more rarely, SCH has been described to occur in the cervical spine in association with brachial plexus avulsion injuries (BPAI-SCH). In our accompanying article, Late Cervical Spinal Cord Herniation Resulting from Post-Traumatic Brachial Plexus Avulsion Injury, two cases of BPAI-SCH are presented and discussed in the context of the reviewed literature [5]. Here, pertinent accompanying follow-up data was collected and is presented for the cases, including postoperative radiographic outcome imaging. Furthermore, a table is presented comparing and contrasting ATSCH to BPAI-SCH. Although the two phenomena have been previously grouped together, this table highlights ATSCH and BPAI-SCH as distinct entities; more specifically, BPAI-SCH is a separate, long-term complicating feature of BPAI. This supplementary data helps treating physicians by increasing awareness and knowledge of BPAI-SCH as a distinct entity from ATSCH and cause of delayed neurological deterioration

Foraminal Ligaments Tether Upper Cervical Nerve Roots: A Potential Cause of Postoperative C5 Palsy.

Background Nerve root tethering upon dorsal spinal cord (SC) migration has been proposed as a potential mechanism for postoperative C5 palsy (C5P). To our knowledge, this is the first study to investigate this relationship by anatomically comparing C5-C6 nerve root translation before and after root untethering by cutting the cervical foraminal ligaments (FL). Objective The aim of this study is to determine if C5 root untethering through FL cutting results in increased root translation. Methods Six cadaveric dissections were performed. Nerve roots were exposed via C4-C6 corpectomies and supraclavicular brachial plexus exposure. Pins were inserted into the C5-C6 roots and adjacent foraminal tubercle. Translation was measured as the distance between pins after the SC was dorsally displaced 5 mm before and after FL cutting. Clinical feasibility of FL release was examined by comparing root translation between standard and extended (complete foraminal decompression) foraminotomies. Translation of root levels before and after FL cutting was compared by two-way repeated measures analysis of variance. Statistical significance was set at 0.05. Results Significantly more nerve root translation was observed if the FL was cut versus not-cut, p = 0.001; no difference was seen between levels, p = 0.33. Performing an extended cervical foraminotomy was technically feasible allowing complete FL release and root untethering, whereas a standard foraminotomy did not. Conclusion FL tether upper cervical nerve roots in their foramina; cutting these ligaments untethers the root and increases translation suggesting they could be harmful in the context of C5P. Further investigation is required examining the value of root untethering in the context of C5P

Robust statistics towards detection of the 21 cm signal from the Epoch of Reionization

© 2019 The Author(s) Published by Oxford University Press on behalf of the Royal Astronomical Society. We explore methods for robust estimation of the 21 cm signal from the Epoch of Reionization (EoR). A Kernel Density Estimator (KDE) is introduced for measuring the spatial temperature fluctuation power spectrum from the EoR. The KDE estimates the underlying probability distribution function of fluctuations as a function of spatial scale, and contains different systematic biases and errors to the typical approach to estimating the fluctuation power spectrum. Extraction of histograms of visibilities allows moments analysis to be used to discriminate foregrounds from 21 cm signal and thermal noise. We use the information available in the histograms, along with the statistical dis-similarity of foregrounds from two independent observing fields, to robustly separate foregrounds from cosmological signal, while making no assumptions about the Gaussianity of the signal. Using two independent observing fields to robustly discriminate signal from foregrounds is crucial for the analysis presented in this paper. We apply the techniques to 13 h of Murchison Widefield Array EoR data over two observing fields. We compare the output to that obtained with a comparative power spectrum estimation method, and demonstrate the reduced foreground contamination using this approach. Using the second moment obtained directly from the KDE distribution functions yields a factor of 2-3 improvement in power for k < 0.3 h Mpc-1 compared with a matched delay space power estimator, while weighting data by additional statistics does not offer significant improvement beyond that available for thermal noise-only weights

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe