Influence of Analytic Techniques on Comparing Dti-Derived Measurements in Early Stage Parkinson\u27s Disease

Diffusion tensor imaging (DTI) studies in early Parkinson\u27s disease (PD) to understand pathologic changes in white matter (WM) organization are variable in their findings. Evaluation of different analytic techniques frequently employed to understand the DTI-derived change in WM organization in a multisite, well-characterized, early stage PD cohort should aid the identification of the most robust analytic techniques to be used to investigate WM pathology in this disease, an important unmet need in the field. Thus, region of interest (ROI)-based analysis, voxel-based morphometry (VBM) analysis with varying spatial smoothing, and the two most widely used skeletonwise approaches (tract-based spatial statistics, TBSS, and tensor-based registration, DTI-TK) were evaluated in a DTI dataset of early PD and Healthy Controls (HC) from the Parkinson\u27s Progression Markers Initiative (PPMI) cohort. Statistical tests on the DTI-derived metrics were conducted using a nonparametric approach from this cohort of early PD, after rigorously controlling for motion and signal artifacts during DTI scan which are frequent confounds in this disease population. Both TBSS and DTI-TK revealed a significantly negative correlation of fractional anisotropy (FA) with disease duration. However, only DTI-TK revealed radial diffusivity (RD) to be driving this FA correlation with disease duration. HC had a significantly positive correlation of MD with cumulative DaT score in the right middle-frontal cortex after a minimum smoothing level (at least 13mm) was attained. The present study found that scalar DTI-derived measures such as FA, MD, and RD should be used as imaging biomarkers with caution in early PD as the conclusions derived from them are heavily dependent on the choice of the analysis used. This study further demonstrated DTI-TK may be used to understand changes in DTI-derived measures with disease progression as it was found to be more accurate than TBSS. In addition, no singular region was identified that could explain both disease duration and severity in early PD. The results of this study should help standardize the utilization of DTI-derived measures in PD in an effort to improve comparability across studies and time, and to minimize variability in reported results due to variation in techniques

Prevalence of Dyskinesia and OFF by 30-Minute Intervals Through the Day and Assessment of Daily Episodes of Dyskinesia and OFF: Novel Analyses of Diary Data from Gocovri Pivotal Trials.

BACKGROUND: Parkinson\u27s disease (PD) patients using levodopa commonly develop dyskinesia and OFF episodes that reduce quality of life. OBJECTIVE: Evaluate prevalence of troublesome dyskinesia and OFF through the day, assessed by 30-minute intervals, as well as the mean number and duration of troublesome dyskinesia and OFF episodes, transitions between PD states, and effects of Gocovri® (amantadine) extended release capsules on these episodes. METHODS: Evaluate diary data from pooled Gocovri phase 3, placebo-controlled trials-analyzed for 17 hours following wake-up-at baseline and week 12. RESULTS: Diaries were evaluable for 162 patients. At baseline, 67% of patients woke up OFF, with prevalence decreasing to 13% at 2 hours and then remaining relatively steady at ∼12% (range, 6-17%) across half-hour intervals thereafter. Troublesome dyskinesia prevalence rose steadily from 5% to 24% over the first 2 hours, then fluctuated between 20% and 44% through the rest of the waking day. At baseline, patients experienced a mean of 3.0 daily episodes of troublesome dyskinesia (average duration 2.0 hours each), and 2.2 daily episodes of OFF (average duration 1.1 hour each). At week 12, Gocovri-treated patients showed greater reductions than placebo in troublesome dyskinesia and OFF episodes per day (treatment difference: -1.0 episodes and -0.4 episodes, respectively) and average episode duration (treatment difference: -0.6 hours and -0.3 hours, respectively). Mean duration of individual episodes of ON without troublesome dyskinesia (Good ON) increased by 5.0 hours for Gocovri, compared with 2.0 hours for placebo. Patients taking Gocovri experienced 2.2 fewer transitions between states than patients taking placebo. CONCLUSIONS: Troublesome dyskinesia and OFF occurred in the morning and throughout the waking day. Gocovri-treated patients experienced fewer, shorter episodes of both troublesome dyskinesia and OFF, thereby increasing the duration of continuous Good ON episodes and reducing the frequency of transitions between motor states

The Fictive Reflex : A Fresh Look at Reflexiveness and Narrative Representation

Reflexiveness in literary contexts tends to be assimilated to self-reference; to the various ways in which a work may foreground the artifice and conventionality of its own features as representation, narrative or language. In this sense it is equated with metafiction, and regarded as a sophisticated and highly self-conscious use of narrative; here, however, I offer a contrary view of reflexiveness, one which sees it as elementary, pervasive, and constitutive of fictionality. In this view, there is a continuity between the basic logic of mimesis and the self-conscious “baring of the device” that, for the Russian Formalists, defines the literary. I begin by clarifying the nature of (fictive) representation as an act, and identify its intrinsic reflexiveness, and go on to compare this perspective with both the metafictional notion of reflexiveness and the theoretical discourse on reflexiveness around “mirror neurons” in cognitive literary studies. I then situate reflexiveness within a broader interdisciplinary environment, framed by complex systems science and the conceptualization of emergence in terms of representational recursiveness, which allows the two sides of the discussion so far to be understood as complementary aspects of reflexiveness, one of which aligns with the cultivation of (self-) consciousness, the other with the simple enactment of systemic relations. Finally I address the conceptual challenge presented by an account of narrative, and fiction, based upon reflexiveness, and suggest some ways in which it can be understood

The FAD Cofactor of RebC Shifts to an IN Conformation upon Flavin Reduction†,‡

RebC is a putative flavin hydroxylase functioning together with RebP to carry out a key step in the biosynthesis of rebeccamycin. To probe the mechanism of flavin-based chemistry in RebC, we solved the structure of RebC with reduced flavin. Upon flavin reduction, the RebC crystal undergoes a change in its unit cell dimension concurrent with a 5 Å movement of the isoalloxazine ring, positioning the flavin ring adjacent to the substrate-binding pocket. Additionally, a disordered helix becomes ordered upon flavin reduction, closing off one side of the substrate-binding pocket. This structure, along with previously reported structures, increases our understanding of the RebC enzyme mechanism, indicating that either the reduction of the flavin itself or binding of substrate is sufficient to drive major conformational changes in RebC to generate a closed active site. Our finding that flavin reduction seals the active site such that substrate cannot enter suggests that our reduced flavin RebC structure is off-pathway and that substrate binding is likely to precede flavin reduction during catalysis. Along with kinetic data presented here, these structures suggest that the first cycle of catalysis in RebC may resemble that of p-hydroxybenzoate hydroxylase, with substrate binding promoting flavin reduction

Solvent Engineered Synthesis of Layered SnO Nanoparticles for High-Performance Anodes

Batteries are the most abundant form of electrochemical energy storage. Lithium and sodium ion batteries account for a significant portion of the battery market, but high-performance electrochemically active materials still need to be discovered and optimized for these technologies. Recently, tin(II) oxide (SnO) has emerged as a highly-promising battery electrode. In this work, we present a facile synthesis method to produce SnO nanoparticles whose size and shape can be tailored by changing the solvent nature. We study the complex relationship between wet chemistry synthesis conditions and resulting layered nanoparticle morphology. Furthermore, high-level electronic structure theory, including dispersion corrections to account for van der Waals forces, are employed to enhance our understanding of the underlying chemical mechanisms. The electronic vacuum alignment and surface energies are determined, allowing the prediction of the thermodynamically-favoured crystal shape (Wulff construction) and surface-weighted work function. Finally, the synthesized nanomaterials were tested as Li-ion battery anodes, demonstrating significantly enhanced electrochemical performance for morphologies obtained from specific synthesis conditions

Image Flux Ratios of Gravitationally Lensed HS 0810+2554 with High Resolution Infrared Imaging

We report near simultaneous imaging using LMIRCam on the LBTI of the quadruply imaged lensed quasar HS 0810+2554 at wavelengths of 2.16, 3.7 and $4.78~\mu$m with a Full Width Half Max (FWHM) spatial resolution of $0^{\prime\prime}\!\!.13$, $0^{\prime\prime}\!\!.12$ and $0^{\prime\prime}\!\!.15$ respectively, comparable to HST optical imaging. In the $\rm{z} = 1.5$ rest frame of the quasar, the observed wavelengths correspond to 0.86, 1.48, and $1.91~\mu$m respectively. The two brightest images in the quad, A and B, are clearly resolved from each other with a separation of $0.187^{\prime\prime}$. The flux ratio of these two images (A/B) trends from 1.79 to 1.23 from 2.16 to $4.78~\mu$m. The trend in flux ratio is consistent with the $2.16~\mu$m flux originating from a small sized accretion disk in the quasar that experiences only microlensing. The excess flux above the contribution from the accretion disk at the two longer wavelengths originates from a larger sized region that experiences no microlensing. A simple model employing multiplicative factors for image B due to stellar microlensing $(m)$ and sub-structure millilensing $(M)$ is presented. The result is tightly constrained to the product $m\times M=1.79$. Given the observational errors, the 60\% probability contour for this product stretches from $m= 2.6$, $M = 0.69$ to $m= 1.79$, $M = 1.0$, where the later is consistent with microlensing only.Comment: accepted A

Effect of head size and rotation on taper corrosion in a hip simulator

Aims This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads. Methods In all, six 28 mm and six 36 mm titanium stem-cobalt chrome head pairs with polyethylene sockets were tested in a novel instrumented hip simulator. Samples were tested using simulated gait data with incremental increasing loads to determine corrosion onset load and electrochemical activity. Half of each head size group were then cycled with simulated gait and the other half with gait compression only. Damage was measured by area and maximum linear wear depth. Results Overall, 36 mm heads had lower corrosion onset load (p = 0.009) and change in open circuit potential (OCP) during simulated gait with (p = 0.006) and without joint movement (p = 0.004). Discontinuing gait’s joint movement decreased corrosion currents (p = 0.042); however, wear testing showed no significant effect of joint movement on taper damage. In addition, 36 mm heads had greater corrosion area (p = 0.050), but no significant difference was found for maximum linear wear depth (p = 0.155). Conclusion Larger heads are more susceptible to taper corrosion; however, not due to frictional torque as hypothesized. An alternative hypothesis of taper flexural rigidity differential is proposed. Further studies are necessary to investigate the clinical significance and underlying mechanism of this finding

First results from Faint Infrared Grism Survey (FIGS): first simultaneous detection of Lyman-alpha emission and Lyman break from a galaxy at z=7.51

Galaxies at high redshifts provide a valuable tool to study cosmic dawn, and therefore it is crucial to reliably identify these galaxies. Here, we present an unambiguous and first simultaneous detection of both the Lyman-alpha emission and the Lyman break from a z = 7.512+/- 0.004 galaxy, observed in the Faint Infrared Grism Survey (FIGS). These spectra, taken with G102 grism on Hubble Space Telescope (HST), show a significant emission line detection (6 sigma) in multiple observational position angles (PA), with total integrated Ly{\alpha} line flux of 1.06+/- 0.12 e10-17erg s-1cm-2. The line flux is nearly a factor of four higher than the previous MOSFIRE spectroscopic observations of faint Ly{\alpha} emission at {\lambda} = 1.0347{\mu}m, yielding z = 7.5078+/- 0.0004. This is consistent with other recent observations implying that ground-based near-infrared spectroscopy underestimates total emission line fluxes, and if confirmed, can have strong implications for reionization studies that are based on ground-based Lyman-{\alpha} measurements. A 4-{\sigma} detection of the NV line in one PA also suggests a weak Active Galactic Nucleus (AGN), potentially making this source the highest-redshift AGN yet found. Thus, this observation from the Hubble Space Telescope clearly demonstrates the sensitivity of the FIGS survey, and the capability of grism spectroscopy to study the epoch of reionization.Comment: Published in ApJL; matches published versio

Spectrophotometrically Identified stars in the PEARS-N and PEARS-S fields

Deep ACS slitless grism observations and identification of stellar sources are presented within the Great Observatories Origins Deep Survey (GOODS) North and South fields which were obtained in the Probing Evolution And Reionization Spectroscopically (PEARS) program. It is demonstrated that even low resolution spectra can be a very powerful means to identify stars in the field, especially low mass stars with stellar types M0 and later. The PEARS fields lay within the larger GOODS fields, and we used new, deeper images to further refine the selection of stars in the PEARS field, down to a magnitude of mz = 25 using a newly developed stellarity parameter. The total number of stars with reliable spectroscopic and morphological identification was 95 and 108 in the north and south fields respectively. The sample of spectroscopically identified stars allows constraints to be set on the thickness of the Galactic thin disk as well as contributions from a thick disk and a halo component. We derive a thin disk scale height, as traced by the population of M4 to M9 dwarfs along two independent lines of sight, of h_thin = 370 +60/-65 pc. When including the more massive M0 to M4 dwarf population, we derive h_thin = 300 +/- 70pc. In both cases, we observe that we must include a combination of thick and halo components in our models in order to account for the observed numbers of faint dwarfs. The required thick disk scale height is typically h_thick=1000 pc and the acceptable relative stellar densities of the thin disk to thick disk and the thin disk to halo components are in the range of 0.00025<f_halo<0.0005 and 0.05<f_thick<0.08 and are somewhat dependent on whether the more massive M0 to M4 dwarfs are included in our sample