The ability to resolve single retinal cells in rodents in vivo has applications in rodent models of the visual system and retinal disease. The authors have characterized the performance of a ...fluorescence adaptive optics scanning laser ophthalmoscope (fAOSLO) that provides cellular and subcellular imaging of rat retina in vivo.
Enhanced green fluorescent protein (eGFP) was expressed in retinal ganglion cells of normal Sprague-Dawley rats via intravitreal injections of adeno-associated viral vectors. Simultaneous reflectance and fluorescence retinal images were acquired using the fAOSLO. fAOSLO resolution was characterized by comparing in vivo images with subsequent imaging of retinal sections from the same eyes using confocal microscopy.
Retinal capillaries and eGFP-labeled ganglion cell bodies, dendrites, and axons were clearly resolved in vivo with adaptive optics. Adaptive optics correction reduced the total root mean square wavefront error, on average, from 0.30 microm to 0.05 microm (measured at 904 nm, 1.7-mm pupil). The full width at half maximum (FWHM) of the average in vivo line-spread function (LSF) was approximately 1.84 microm, approximately 82% greater than the FWHM of the diffraction-limited LSF.
With perfect aberration compensation, the in vivo resolution in the rat eye could be approximately 2x greater than that in the human eye because of its large numerical aperture (approximately 0.43). Although the fAOSLO corrects a substantial fraction of the rat eye's aberrations, direct measurements of retinal image quality reveal some blur beyond that expected from diffraction. Nonetheless, subcellular features can be resolved, offering promise for using adaptive optics to investigate the rodent eye in vivo with high resolution.
Digital system designs are the product of valuable effort and know-how. Their embodiments, from software and hardware description language program down to device-level netlist and mask data, ...represent carefully guarded intellectual property (IP). Hence, design methodologies based on IP reuse require new mechanisms to protect the rights of IP producers and owners. This paper establishes principles of watermarking-based IP protection, where a watermark is a mechanism for identification that is: (1) nearly invisible to human and machine inspection; (2) difficult to remove; and (3) permanently embedded as an integral part of the design. Watermarking addresses IP protection by tracing unauthorized reuse and making untraceable unauthorized reuse as difficult as recreating given pieces of IP from scratch. We survey related work in cryptography and design methodology, then develop desiderata, metrics, and concrete protocols for constraint-based watermarking at various stages of the very large scale integration (VLSI) design process. In particular, we propose a new preprocessing approach that embeds watermarks as constraints into the input of a black-box design tool and a new postprocessing approach that embeds watermarks as constraints into the output of a black-box design tool. To demonstrate that our protocols can be transparently integrated into existing design flows, we use a testbed of commercial tools for VLSI physical design and embed watermarks into real-world industrial designs. We show that the implementation overhead is low-both in terms of central processing unit time and such standard physical design metrics as wirelength, layout area, number of vias, and routing congestion. We empirically show that the placement and routing applications considered in our methods achieve strong proofs of authorship and are resistant to tampering and do not adversely influence timing.
Use of magnetic resonance imaging (MRI) as a tool to aid in neuroprognostication after cardiac arrest (CA) has been described, yet details of specific indications, timing, and sequences are unknown. ...We aim to define the current practices in use of brain MRI in prognostication after pediatric CA.
A survey was distributed to pediatric institutions participating in three international studies. Survey questions related to center demographics, clinical practice patterns of MRI after CA, neuroimaging resources, and details regarding MRI decision support.
Response rate was 31% (44 of 143). Thirty-four percent (15 of 44) of centers have a clinical pathway informing the use of MRI after CA. Fifty percent (22 of 44) of respondents reported that an MRI is obtained in nearly all patients with CA, and 32% (14 of 44) obtain an MRI in those who do not return to baseline neurological status. Poor neurological examination was reported as the most common factor (91% 40 of 44) determining the timing of the MRI. Conventional sequences (T1, T2, fluid-attenuated inversion recovery, and diffusion-weighted imaging/apparent diffusion coefficient) are routinely used at greater than 97% of centers. Use of advanced imaging techniques (magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI) were reported by less than half of centers.
Conventional brain MRI is a common practice for prognostication after CA. Advanced imaging techniques are used infrequently. The lack of standardized clinical pathways and variability in reported practices support a need for higher-quality evidence regarding the indications, timing, and acquisition protocols of clinical MRI studies.
Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child's DSD, have not been ...examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency).
Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling.
Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ21 = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction.
Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.
Nitric oxide (NO) is emitted in large quantities from coal-burning power plants. During the day, the plumes from these sources are efficiently mixed into the boundary layer, while at night, they may ...remain concentrated due to limited vertical mixing during which they undergo horizontal fanning. At night, the degree to which NO is converted to HNO3 and therefore unable to participate in next-day ozone (O3) formation depends on the mixing rate of the plume, the composition of power plant emissions, and the composition of the background atmosphere. In this study, we use observed plume intercepts from the Wintertime INvestigation of Transport, Emissions and Reactivity (WINTER) campaign to test sensitivity of overnight NOx removal to the N2O5 loss rate constant, plume mixing rate, background O3, and background levels of volatile organic compounds using a 2-D box model of power plant plume transport and chemistry. The factor that exerted the greatest control over NOx removal was the loss rate constant of N2O5. At the lowest observed N2O5 loss rate constant, no other combination of conditions converts more than 10 percent of the initial NOx to HNO3. The other factors did not influence NOx removal to the same degree.
Diagnostic criteria are presented for degenerative, inflammatory, nonneoplastic proliferative, and neoplastic lesions in the liver of medaka (Oryzias latipes), a small fish species frequently used in ...carcinogenesis studies. The criteria are the consensus of a Pathology Working Group (PWG) convened by the National Toxicology Program. The material examined by the PWG was from Medaka exposed to N-nitrosodiethylamine for 28 days, removed to clean water, and sacrificed 4, 6, or 9 mo after initiation of exposure. Degenerative lesions included hepatocellular intracytoplasmic vacuolation, hepatocellular necrosis, spongiosis hepatis, hepatic cysts, and hepatocellular hyalinization. Inflammatory lesions consisted of granulomas, chronic inflammation, macrophage aggregates, and focal lymphocytic infiltration. Nonneoplastic proliferative lesions comprised foci of cellular alteration (basophilic focus, eosinophilic focus, vacuolated focus, and clear cell focus) and bile duct hyperplasia. Neoplastic lesions included hepatocellular adenoma, hepatocellular carcinoma, cholangioma, and cholangiocarcinoma. Two lesions composed mainly of spindle cells were noted, hemangiopericytoma and spindle cell proliferation. Rather than being an exhaustive treatment of medaka liver lesions, this report draws from the published literature on carcinogen-induced liver lesions in medaka and other fish species and attempts to consolidate lesion criteria into a simplified scheme that might be useful to pathologists and other researchers using medaka lesions for risk assessment or regulatory purposes.
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