Clinical Utility of Molecular Profiling in Recurrent Glioblastoma Multiforme

Introduction: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor found in adults. GBM has limited therapeutic options. Initial tumor sampling establishes the histopathologic diagnosis, identifies prognostic and therapeutic biomarkers, and provides an opportunity for molecular profiling. By contrast, the utility of repeat tumor sampling and molecular profiling in recurrent GBM is not well established. Clinical Findings: We present a 69-year-old woman with GBM whose tumor recurred after standard treatment with temozolomide (TMZ) and concurrent radiation, followed by adjuvant TMZ. This patient had a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, which ordinarily predicts a favorable response to TMZ. Main Diagnosis, Therapeutic Interventions, and Outcomes: Our patient’s recurrent tumor was rechallenged with TMZ based on persistent methylation of the MGMT promoter. However, her tumor was refractory to TMZ, and she floridly progressed through multiple treatments. We performed retrospective molecular profiling using next-generation sequencing (NGS) on her recurrent tumor. The NGS results showed a TMZ hypermutation signature that confers resistance to TMZ. This signature impacted our patient’s treatment plan in real time and prompted an immediate discontinuation of TMZ. Conclusions: Advances in NGS provide further insight into the molecular landscape of GBM. As NGS becomes more timely and cost-effective, molecular profiling of recurrent tumors could impact treatment decisions through either avoiding a particular treatment paradigm or identifying a potential targetable mutation. For this reason, we suggest that clinical practice routinely consider repeat biopsy and molecular profiling for recurrent GBM

Flow separation control over a rounded ramp with spanwise alternating wall actuation

An implicit large-eddy simulation is carried out to study turbulent boundary-layer separation from a backward-facing rounded ramp with active wall actuation control. This method, called spanwise alternating distributed strips control, is imposed onto the flat plate surface upstream of a rounded ramp by alternatively applying out-of-phase control and in-phase control to the wall-normal velocity component in the spanwise direction. As a result, the local turbulence intensity is alternatively suppressed and enhanced, leading to the creation of vertical shear-layers, which is responsible for the presence of large-scale streamwise vortices. These vortices exert a predominant influence on the suppression of the flow separation. The interaction between the large-scale vortices and the downstream recirculation zone and free shear-layer is studied by examining flow statistics. It is found that in comparison with the non-controlled case the flow separation is delayed, the reattachment point is shifted upstream, and the length of the mean recirculation zone is reduced up to 8.49%. The optimal control case is achieved with narrow in-phase control strips. An in-depth analysis shows that the delay of the flow separation is attributed to the activation of the near-wall turbulence by the in-phase control strips and the improvement of the reattachment location is mainly due to the large-scale streamwise vortices, which enhance the momentum transport between the main flow and separated region

Equivariant comparison of quantum homogeneous spaces

We prove the deformation invariance of the quantum homogeneous spaces of the q-deformation of simply connected simple compact Lie groups over the Poisson-Lie quantum subgroups, in the equivariant KK-theory with respect to the translation action by maximal tori. This extends a result of Neshveyev-Tuset to the equivariant setting. As applications, we prove the ring isomorphism of the K-group of Gq with respect to the coproduct of C(Gq), and an analogue of the Borsuk-Ulam theorem for quantum spheres.Comment: 21 page

Sex, sex chromosomes and gene expression

The X chromosome has fewer testis-specific genes than autosomes in many species. This bias is commonly attributed to X inactivation in spermatogenesis but a recent paper in BMC Biology provides evidence against X inactivation in Drosophila and proposes that somatic tissue- and testis- but not ovary-specific genes tend not to be located on the X chromosome. Here, we discuss possible mechanisms underlying this bias, including sexual antagonism and dosage compensation

Frontal and superior temporal auditory processing abnormalities in schizophrenia

AbstractBackgroundAlthough magnetoencephalography (MEG) studies show superior temporal gyrus (STG) auditory processing abnormalities in schizophrenia at 50 and 100ms, EEG and corticography studies suggest involvement of additional brain areas (e.g., frontal areas) during this interval. Study goals were to identify 30 to 130ms auditory encoding processes in schizophrenia (SZ) and healthy controls (HC) and group differences throughout the cortex.MethodsThe standard paired-click task was administered to 19 SZ and 21 HC subjects during MEG recording. Vector-based Spatial–temporal Analysis using L1-minimum-norm (VESTAL) provided 4D maps of activity from 30 to 130ms. Within-group t-tests compared post-stimulus 50ms and 100ms activity to baseline. Between-group t-tests examined 50 and 100ms group differences.ResultsBilateral 50 and 100ms STG activity was observed in both groups. HC had stronger bilateral 50 and 100ms STG activity than SZ. In addition to the STG group difference, non-STG activity was also observed in both groups. For example, whereas HC had stronger left and right inferior frontal gyrus activity than SZ, SZ had stronger right superior frontal gyrus and left supramarginal gyrus activity than HC.ConclusionsLess STG activity was observed in SZ than HC, indicating encoding problems in SZ. Yet auditory encoding abnormalities are not specific to STG, as group differences were observed in frontal and SMG areas. Thus, present findings indicate that individuals with SZ show abnormalities in multiple nodes of a concurrently activated auditory network

SMARCB1/INI1 germline mutations contribute to 10% of sporadic schwannomatosis

<p>Abstract</p> <p>Background</p> <p>Schwannomatosis is a disease characterized by multiple non-vestibular schwannomas. Although biallelic <it>NF2 </it>mutations are found in schwannomas, no germ line event is detected in schwannomatosis patients. In contrast, germline mutations of the <it>SMARCB1 </it>(<it>INI1</it>) tumor suppressor gene were described in familial and sporadic schwannomatosis patients.</p> <p>Methods</p> <p>To delineate the <it>SMARCB1 </it>gene contribution, the nine coding exons were sequenced in a series of 56 patients affected with a variable number of non-vestibular schwannomas.</p> <p>Results</p> <p>Nine variants scattered along the sequence of <it>SMARCB1 </it>were identified. Five of them were classified as deleterious. All five patients carrying a <it>SMARCB1 </it>mutation had more multiple schwannomas, corresponding to 10.2% of patients with schwannomatosis. They were also diagnosed before 35 years of age.</p> <p>Conclusions</p> <p>These results suggest that patients with schwannomas have a significant probability of carrying a <it>SMARCB1 </it>mutation. Combined with data available from other studies, they confirm the clinical indications for genetic screening of the <it>SMARCB1 </it>gene.</p

Hepatitis E Virus Genotype 3 Diversity, France

We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected patients in France in 3 parts of the genome and sequenced the full-length HEV genotype 3f genome found in Europe. These strains are closely related to swine strains in Europe, which suggests zoonotic transmission of HEV in France

A giant retroperitoneal lymphangioma in a patient with neurofibromatosis type 1

Neurofibromatosis type 1 (NF-1) is a genetically inherited disorder that may cause skin abnormalities and tumors that form on nerve tissues. These tumors can be small or large and can occur anywhere in the body, including the brain, spinal cord, or other peripheral nerves. Retroperitoneal lymphangiomas are very rare benign malformations of the lymphatic system. About 95% lymphangiomas occur in the skin and the subcutaneous tissues of the head, neck and axillary region and the remaining 5% appear in other parts of the body such as lungs, pleura, pericardium, liver, gallbladder, kidney, and the mesentery. Herein, we report the case of a giant retroperitoneal lymphangioma in a patient with NF-1 with a review of the literature

Prospects of observing a quasar HII region during the Epoch of Reionization with redshifted 21cm

We present a study of the impact of a bright quasar on the redshifted 21cm signal during the Epoch of Reionization (EoR). Using three different cosmological radiative transfer simulations, we investigate if quasars are capable of substantially changing the size and morphology of the H II regions they are born in. We choose stellar and quasar luminosities in a way that is favourable to seeing such an effect. We find that even the most luminous of our quasar models is not able to increase the size of its native H II region substantially beyond those of large H II regions produced by clustered stellar sources alone. However, the quasar H II region is found to be more spherical. We next investigate the prospects of detecting such H II regions in the redshifted 21cm data from the Low Frequency Array (LOFAR) by means of a matched filter technique. We find that H II regions with radii ~ 25 comoving Mpc or larger should have a sufficiently high detection probability for 1200 hours of integration time. Although the matched filter can in principle distinguish between more and less spherical regions, we find that when including realistic system noise this distinction can no longer be made. The strong foregrounds are found not to pose a problem for the matched filter technique. We also demonstrate that when the quasar position is known, the redshifted 21cm data can still be used to set upper limits on the ionizing photon rate of the quasar. If both the quasar position and its luminosity are known, the redshifted 21 cm data can set new constrains on quasar lifetimes.Comment: 17 pages, 12 figures, 3 tables, accepted for publication in MNRAS; changes in introduction and figure

Molecular gas in NGC6946

We present imaging of molecular gas emission in the star-forming spiral galaxy NGC6946. Our CO(1-0) and CO(3-2) images, made at 22" resolution with the IRAM 30-m and the Heinrich Hertz 10-m radio telescopes, are the most extensive CO observations of this galaxy and are among the most extensive observations of molecular gas in any spiral galaxy. The molecular component in NGC6946 is unusually massive, with a ratio of molecular to atomic Hydrogen of 0.57. A star formation efficiency image for NGC6946 ranges by over two orders of magnitude with highest values found in the northeastern spiral arm, and anticorrelates with the 6cm polarized emission image, which traces the regular part of the magnetic field. We analyse the ISM in NGC6946's disk by making 1-D and 2-D comparisons of images made in several wavebands. A point-by-point correlation technique finds that the molecular gas is closely associated with the 7micron-emitting dust. The high correlation found between the MIR emission and the radio continuum at 6cm cannot be due to dust heating and gas ionization in star-forming regions because the thermal radio emission is less correlated with the MIR than the nonthermal emission. A coupling of magnetic fields to gas clouds is proposed as a possible scenario.Comment: A&A accepted, 23 pages, 11 figures. Version with high resolution figures available at: http://cfa-www.harvard.edu/~wwalsh/sp.htm