The use of high frequency oscillations to guide neocortical resections in children with medically-intractable epilepsy: How do we ethically apply surgical innovations to patient care?

AbstractPurposeResective surgical strategies are increasingly applied to treat medically-intractable epilepsy in children as uncontrolled seizures are associated with poor cognitive, developmental and behavioral outcomes. Innovative surgical strategies are, however, needed to improve outcomes and minimize the morbidity of such procedures.MethodThe current article utilizes an axiological approach to explore and highlight ethical issues in the use of high frequency oscillations (HFOs) to guide surgical resections in children with medically-intractable epilepsy. We frame our discussion in the context of the broader challenges in the application of surgical innovation to patient care.ResultsDespite a paucity of knowledge regarding their pathogenesis, limited evidence suggests the use of HFOs as biomarkers of epileptogenicity in resective procedures can improve seizure outcome. Clinicians must therefore weigh deficiencies in knowledge against the limited evidence supporting the utility of HFOs and make ethical decisions for the treatment of individual patients. Important ethical considerations for clinicians include the extent of deviation from established practice, the extent of evidence required to establish clinical validity, and the impact of technique implementation on equitable distribution of healthcare.ConclusionThe use of HFO signatures to guide neocortical resections represents a novel approach for the treatment of epilepsy. It is hoped that the issues discussed herein will contribute to and advance meaningful dialog on the ethical application of this surgical innovation to the treatment of a very vulnerable patient population

On the elliptic nonabelian Fourier transform for unipotent representations of p-adic groups

In this paper, we consider the relation between two nonabelian Fourier transforms. The first one is defined in terms of the Langlands-Kazhdan-Lusztig parameters for unipotent elliptic representations of a split p-adic group and the second is defined in terms of the pseudocoefficients of these representations and Lusztig's nonabelian Fourier transform for characters of finite groups of Lie type. We exemplify this relation in the case of the p-adic group of type G_2.Comment: 17 pages; v2: several minor corrections, references added; v3: corrections in the table with unipotent discrete series of G

Lowest Q^2 Measurement of the gamma*p -> Delta Reaction: Probing the Pionic Contribution

To determine nonspherical angular momentum amplitudes in hadrons at long ranges (low Q^2), data were taken for the p(\vec{e},e'p)\pi^0 reaction in the Delta region at Q^2=0.060 (GeV/c)^2 utilizing the magnetic spectrometers of the A1 Collaboration at MAMI. The results for the dominant transition magnetic dipole amplitude and the quadrupole to dipole ratios at W=1232 MeV are: M_{1+}^{3/2} = (40.33 +/- 0.63_{stat+syst} +/- 0.61_{model}) (10^{-3}/m_{\pi^+}),Re(E_{1+}^{3/2}/M_{1+}^{3/2}) = (-2.28 +/- 0.29_{stat+syst} +/- 0.20_{model})%, and Re(S_{1+}^{3/2}/M_{1+}^{3/2}) = (-4.81 +/- 0.27_{stat+syst} +/- 0.26_{model})%. These disagree with predictions of constituent quark models but are in reasonable agreement with lattice calculations with non-linear (chiral) pion mass extrapolations, with chiral effective field theory, and with dynamical models with pion cloud effects. These results confirm the dominance, and general Q^2 variation, of the pionic contribution at large distances.Comment: 6 pages, 3 figures, 1 tabl

Locus-specific editing of histone modifications at endogenous enhancers using programmable TALE-LSD1 fusions

Mammalian gene regulation is dependent on tissue-specific enhancers that can act across large distances to influence transcriptional activity1-3. Mapping experiments have identified hundreds of thousands of putative enhancers whose functionality is supported by cell type–specific chromatin signatures and striking enrichments for disease-associated sequence variants4-11. However, these studies did not address the in vivo functions of the putative elements or their chromatin states and could not determine which genes, if any, a given enhancer regulates. Here we present a strategy to investigate endogenous regulatory elements by selectively altering their chromatin state using programmable reagents. Transcription activator–like (TAL) effector repeat domains fused to the LSD1 histone demethylase efficiently remove enhancer-associated chromatin modifications from target loci, without affecting control regions. We find that inactivation of enhancer chromatin by these fusion proteins frequently causes down-regulation of proximal genes, revealing enhancer target genes. Our study demonstrates the potential of ‘epigenome editing’ tools to characterize an important class of functional genomic elements

4-(2,4-Dichlorophenyl)-2-(1H-indol-3-yl)-6-methoxypyridine-3,5-dicarbonitrile

In the title compound, C22H12Cl2N4O, the indole ring system and the benzene ring form dihedral angles of 21.18 (7)° and 68.43 (8)°, respectively, with the pyridine ring. The meth­oxy group is coplanar with the pyridine ring. In the crystal structure N—H⋯N inter­molecular hydrogen bonds link the mol­ecules into C(10) chains running along [011]. Intramolec­ular C—H⋯N hydrogen bonds are also observed

Dark Matter in the Galaxy Cluster CL J1226+3332 at Z=0.89

We present a weak-lensing analysis of the galaxy cluster CL J1226+3332 at z=0.89 using Hubble Space Telescope Advanced Camera for Surveys images. The cluster is the hottest (>10 keV), most X-ray luminous system at z>0.6 known to date. The relaxed X-ray morphology, as well as its high temperature, is unusual at such a high redshift. Our mass reconstruction shows that on a large scale the dark matter distribution is consistent with a relaxed system with no significant substructures. However, on a small scale the cluster core is resolved into two mass clumps highly correlated with the cluster galaxy distribution. The dominant mass clump lies close to the brightest cluster galaxy whereas the other less massive clump is located ~40" (~310 kpc) to the southwest. Although this secondary mass clump does not show an excess in the X-ray surface brightness, the gas temperature of the region is much higher (12~18 keV) than those of the rest. We propose a scenario in which the less massive system has already passed through the main cluster and the X-ray gas has been stripped during this passage. The elongation of the X-ray peak toward the southwestern mass clump is also supportive of this possibility. We measure significant tangential shears out to the field boundary (~1.5 Mpc), which are well described by an Navarro-Frenk-White profile with a concentration parameter of c200=2.7+-0.3 and a scale length of rs=78"+-19" (~600 kpc) with chi^2/d.o.f=1.11. Within the spherical volume r200=1.6 Mpc, the total mass of the cluster becomes M(r<r200)=(1.4+-0.2) x 10^15 solar mass. Our weak-lensing analysis confirms that CL1226+3332 is indeed the most massive cluster known to date at z>0.6.Comment: Accepted for publication in Ap

Oddification of the cohomology of type A Springer varieties

We identify the ring of odd symmetric functions introduced by Ellis and Khovanov as the space of skew polynomials fixed by a natural action of the Hecke algebra at q=-1. This allows us to define graded modules over the Hecke algebra at q=-1 that are `odd' analogs of the cohomology of type A Springer varieties. The graded module associated to the full flag variety corresponds to the quotient of the skew polynomial ring by the left ideal of nonconstant odd symmetric functions. The top degree component of the odd cohomology of Springer varieties is identified with the corresponding Specht module of the Hecke algebra at q=-1.Comment: 21 pages, 2 eps file