Maintaining fixation by children in a virtual reality version of pupil perimetry

The assessment of visual field sensitivities in young children continues to be a challenge. Children often do not sit still, fail to fixate stimuli for longer durations, and have limited verbal capacity to report visibility. We investigated the use of a head-mounted VR display, gaze-contingent flicker pupil perimetry (gcFPP), and three fixation stimulus conditions to determine best practices for optimal fixation and pupil response quality. A total of twenty children (3-11y) passively fixated a dot, counted the repeated appearance of an animated character, and watched an animated movie in separate trials of 80s each. We presented large flickering patches at different eccentricities and angles in the periphery to evoke pupillary oscillations (20 locations, 4s per location). The results showed that gaze precision and accuracy did not differ significantly across the fixation conditions but pupil amplitudes were strongest for the dot and count task. We recommend the use of the fixation counting task for pupil perimetry because children enjoyed it the most and it achieved strongest pupil responses. The VR set-up appears to be an ideal apparatus for children to allow free range of movement, an engaging visual task, and reliable eye measurements

Maintaining fixation by children in a virtual reality version of pupil perimetry

The assessment of the visual field in young children continues to be a challenge. Children often do not sit still, fail to fixate stimuli for longer durations, and have limited verbal ca-pacity to report visibility. Therefore, we introduced a head-mounted VR display with gaze-contingent flicker pupil perimetry (VRgcFPP). We presented large flickering patches at different eccentricities and angles in the periphery to evoke pupillary oscillations, and three fixation stimulus conditions to determine best practices for optimal fixation and pupil response quality. A total of twenty children (3-11y) passively fixated a dot, counted the re-peated appearance of an animated character(counting task), and watched an animated movie in separate trials of 80s each (20 patch locations, 4s per location).The results showed that gaze precision and accuracy did not differ significantly across the fixation conditions but pupil amplitudes were strongest for the dot and count task. The VR set-up appears to be an ideal apparatus for children to allow free range of movement, an engaging visual task, and reliable eye measurements. We recommend the use of the fixation count-ing task for pupil perimetry because children enjoyed it the most and it achieved strongest pupil responses

Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA

The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of the protease-resistant core of the abnormal prion protein, PrP(Sc) (i.e. type 1 migrating at 21 kDa and type 2 at 19 kDa). We previously demonstrated that PrP(Sc) typing by Western blotting is a reliable means of strain typing and disease classification. Limitations of this approach, however, particularly in the interlaboratory setting, are the association of PrP(Sc) types 1 or 2 with more than one clinicopathological phenotype, which precludes definitive case classification if not supported by further analysis, and the difficulty of fully recognizing cases with mixed phenotypic features. In this study, we tested the inter-rater reliability of disease classification based only on histopathological criteria. Slides from 21 cases covering the whole phenotypic spectrum of human sporadic prion diseases, and also including two cases of variant Creutzfeldt-Jakob disease (CJD), were distributed blindly to 13 assessors for classification according to given instructions. The results showed good-to-excellent agreement between assessors in the classification of cases. In particular, there was full agreement (100 %) for the two most common sporadic CJD subtypes and variant CJD, and very high concordance in general for all pure phenotypes and the most common subtype with mixed phenotypic features. The present data fully support the basis for the current classification of sporadic human prion diseases and indicate that, besides molecular PrP(Sc) typing, histopathological analysis permits reliable disease classification with high interlaboratory accuracy

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Multi-objective optimization of genome-scale metabolic models: the case of ethanol production

Ethanol is among the largest fermentation product used worldwide, accounting for more than 90% of all biofuel produced in the last decade. However current production methods of ethanol are unable to meet the requirements of increasing global demand, because of low yields on glucose sources. In this work, we present an in silico multi-objective optimization and analyses of eight genome-scale metabolic networks for the overproduction of ethanol within the engineered cell. We introduce MOME (multi-objective metabolic engineering) algorithm, that models both gene knockouts and enzymes up and down regulation using the Redirector framework. In a multi-step approach, MOME tackles the multi-objective optimization of biomass and ethanol production in the engineered strain; and performs genetic design and clustering analyses on the optimization results. We find in silico E. coli Pareto optimal strains with a knockout cost of 14 characterized by an ethanol production up to 19.74mmolgDW−1h−1 (+832.88% with respect to wild-type) and biomass production of 0.02h−1 (−98.06% ). The analyses on E. coli highlighted a single knockout strategy producing 16.49mmolgDW−1h−1 (+679.29% ) ethanol, with biomass equals to 0.23h−1 (−77.45% ). We also discuss results obtained by applying MOME to metabolic models of: (i) S. aureus; (ii) S. enterica; (iii) Y. pestis; (iv) S. cerevisiae; (v) C. reinhardtii; (vi) Y. lipolytica. We finally present a set of simulations in which constrains over essential genes and minimum allowable biomass were included. A bound over the maximum allowable biomass was also added, along with other settings representing rich media compositions. In the same conditions the maximum improvement in ethanol production is +195.24%