The inhibitory effect of word neighborhood size when reading with central field loss is modulated by word predictability and reading proficiency.

For normally sighted readers, word neighborhood size (i.e., the total number of words that can be formed from a single word by changing only one letter) has a facilitator effect on word recognition. When reading with central field loss (CFL) however, individual letters may not be correctly identified, leading to possible misidentifications and a reverse neighborhood size effect. Here we investigate this inhibitory effect of word neighborhood size on reading performance and whether it is modulated by word predictability and reading proficiency. Nineteen patients with binocular CFL from 32 to 89 years old (mean ± SD = 75 ± 15) read short sentences presented with the self-paced reading paradigm. Accuracy and reading time were measured for each target word read, along with its predictability, i.e., its probability of occurrence following the two preceding words in the sentence using a trigram analysis. Linear mixed effects models were then fit to estimate the individual contributions of word neighborhood size, predictability, frequency and length on accuracy and reading time, while taking patients' reading proficiency into account. For the less proficient readers, who have given up daily reading as a consequence of their visual impairment, we found that the effect of neighborhood size was reversed compared to normally sighted readers and of higher amplitude than the effect of frequency. Furthermore, this inhibitory effect is of greater amplitude (up to 50% decrease in reading speed) when a word is not easily predictable because its chances to occur after the two preceding words in a specific sentence are rather low. Severely impaired patients with CFL often quit reading on a daily basis because this task becomes simply too exhausting. Based on our results, we envision lexical text simplification as a new alternative to promote effective rehabilitation in these patients. By increasing reading accessibility for those who struggle the most, text simplification might be used as an efficient rehabilitation tool and daily reading assistive technology, fostering overall reading ability and fluency through increased practice.

The influence of word frequency on word reading speed when individuals with macular diseases read text.

People with central field loss (CFL) use peripheral vision to identify words. Eccentric vision provides ambiguous visual inputs to the processes leading to lexical access. Our purpose was to explore the hypothesis that this ambiguity leads to strong influences of inferential processes, our prediction being that increasing word frequency would decrease word reading time. Individuals with bilateral CFL induced by macular diseases read French sentences displayed with a self-paced reading method. Reading time of the last word of each sentence (target word) was recorded. Each target word (in sentence n) was matched with a synonym word (in sentence n+1) of the same length. When using absolute frequency value (Analysis 1), we found that reading time of target words decreased when word frequency increases, even when controlling for word length. The amplitude of this effect is larger than reported in previous investigations of reading with normal subjects. When comparing the effect of relative frequency (low vs. high) within each pair of synonyms (Analysis 2), results show the same pattern as the one observed in Analysis 1. Our results demonstrate clear-cut frequency effects on word reading time and suggest that inferential processes are stronger in CFL readers than in normally sighted observers. These results might also help design text simplification tools tailored for low-vision patients.

Long-distance impact of Iceland plume on Norway's rifted margin.

Results of a 3D modeling study inspired by recent seismic tomography of the Northern Atlantic mantle suggest that a complex pattern of hot mantle distribution with long horizontal flows originating from the Iceland mantle plume has been the norm in the geological past. In the Northern Atlantic the Iceland plume has a strong long-distance impact on intraplate deformation affecting both onshore and offshore parts of Norway's rifted margin. As a result, this margin is characterized by large magnitude differential topography sustained over at least several tens of Myr. Here we use high-resolution 3D thermo-mechanical modeling to demonstrate that the long-distance plume impact can be explained by its fast lateral propagation controlled by pre-existing lithosphere structures. Numerical models show that these structures strongly affect the style of horizontal flow of plume head material. This results in long-distance propagation of hot material emplaced at the lithosphere-asthenosphere boundary causing long-wavelength anomalies in onshore topography of Norway's rifted margin. Short-wavelength offshore topographic domes are likely caused by joint occurrence of plume-related thermal perturbations and gravitational forces related to plate thickening (ridge push). Our 3D modeling brings together plume impingement, spreading ridge dynamics, and the formation of anomalous intraplate structures offshore Norway in one scenario.

Predictive factors for final pathologic ureteral sections on 700 radical cystectomy specimens: Implications for intraoperative frozen section decision-making.

PURPOSE: To identify preoperative predictive factors for final ureteral section invasion after radical cystectomy (RC) and to validate significant factors on an external independent cohort. MATERIAL AND METHODS: We retrospectively reviewed data of all consecutive RC performed for bladder cancer in 2 high-volume institutions. Clinical, pathological, and follow-up data were collected prospectively and reviewed retrospectively. Pathological evaluation was performed by 2 well-trained uropathologists in each center. Logistic regression analyses were performed to identify predictive factors for final ureteral sections involvement. Significant factors in cohort A were validated in cohort B. Receiver operating curve and area under curve were modeled to evaluate predictive accuracy of the markers. RESULTS: A total of 441 RC were performed in center A and 307 RC were performed in center B. Mean follow-ups were 36.2 and 38.1 months, respectively. Invasion of the final ureteral section was observed on 5.5% of patients in cohort A and 4.8% of patients in cohort B. In cohort A, multivariable logistic regression identified preoperative hydronephrosis on computed tomography scan (odds ratio [OR] = 4.9, P = 0.004) and presence of Carcinoma in situ (CIS, OR = 3.9, P = 0.01) as the only factors associated with ureteral sections positivity. In cohort B, hydronephrosis and CIS were both associated with ureteral sections positivity in univariable analysis. In multivariable analysis, only hydronephrosis remained significant (OR = 5.9, P = 0.01). Predictive accuracy of hydronephrosis and CIS combined in 1 variable was 0.72. CONCLUSION: Hydronephrosis and bladder CIS have good accuracy in predicting ureteral sections positivity after RC. In the presence of those factors, ureteral frozen sections should be performed.

Exudative retinopathy, cerebral calcifications, duodenal atresia, preaxial polydactyly, micropenis, microcephaly and short stature: a new syndrome?

The association of Coats disease with intrauterine growth retardation, intracranial calcification, leukodystrophy, brain cysts, osteopenia, and gastrointestinal bleeding defines Coats plus syndrome caused by mutations in the CTC1 gene, encoding conserved telomere maintenance component 1. Here, we report on a child with exudative retinopathy, cerebral calcifications, duodenal atresia, preaxial polydactyly, micropenis, microcephaly, and short stature, in whom no mutations in CTC1 were found. Our patient shares some features seen in other diseases associated with telomere shortening including Hoyeraal-Hreidarsson and Revesz syndromes. We therefore measured telomere length by Flow-Fish which was normal. The association of duodenal atresia and microcephaly also suggested a diagnosis of Feingold syndrome. However, direct sequencing of MYCN was normal, and we did not detect any hemizygous deletion of the miR-17∼92 polycistronic miRNA cluster. To our knowledge, the phenotype we report on has not been described previously, leading us to speculate that this condition may represent a new syndrome.

Cell culture tracking by multivariate analysis of raw LCMS data.

Liquid chromatography mass spectrometry (LCMS) is a powerful technique that could serve to rapidly characterize cell culture protein expression profile and be used as a process monitoring and control tool. However, this application is often hampered by both the sample proteome and the LCMS signal complexities as well as the variability of this signal. To alleviate this problem, culture samples are usually extensively fractionated and pretreated before being analyzed by top-end instruments. Such an approach precludes LCMS usage for routine on-line or at-line application. In this work, by applying multivariate analysis (MA) directly on raw LCMS signals, we were able to extract relevant information from cell culture samples that were simply lyzed. By using the recombinant adenovirus production process as a model, we were able to follow the accumulation of the three major proteins produced, identified their accumulation dynamics, and draw useful conclusions from these results. The combination of LCMS and MA provides a simple, rapid, and precise means to monitor cell culture.

Multivariate analysis of single quadrupole LC-MS spectra for routine characterization and quantification of intact proteins.

Modern high-throughput proteomic platforms allow incomparable protein mixture resolution and identification. However, such sophisticated facilities are expensive and not always accessible for routine analysis of simple mixtures. In this paper, we propose a simple methodology, based on detection of intact, nondigested proteins by LC coupled to single quadrupole MS (sqLC-MS), followed by the analysis of the resulting spectra by multivariate analysis (MA). By doing so, even large molecular weight (MW) proteins, generating complex spectra, can be characterized to a level that allows isoform discrimination, while standard algorithms, such as MS spectrum deconvolution, cannot. To demonstrate the effectiveness of the proposed approach, we have analyzed the spectra of a set of purified, intact albumins from seven different organisms (bovine, human, rabbit, rat, sheep, mouse, and pig) as a model of microheterogenous proteins, using Projection to Latent Structure Discriminant Analysis (PLS-DA). Although these proteins are very similar (less than 1% difference in MW), sqLC-MS/MA allowed their classification, and the identification of unknown source samples. In addition, MA allowed precise protein quantification from the same data (calibration curve R2 = 0.9966). The ability to rapidly characterize and quantify proteins, together with simplicity and affordability, could make of combined sqLC-MS/MA a routine method for the characterization of simple mixture of known proteins.