Developmental specialization of the left parietal cortex for the semantic representation of Arabic numerals: an fMR-adaptation study

The way the human brain constructs representations of numerical symbols is poorly understood. While increasing evidence from neuroimaging studies has indicated that the intraparietal sulcus (IPS) becomes increasingly specialized for symbolic numerical magnitude representation over developmental time, the extent to which these changes are associated with age-related differences in symbolic numerical magnitude representation or with developmental changes in non-numerical processes, such as response selection, remains to be uncovered. To address these outstanding questions we investigated developmental changes in the cortical representation of symbolic numerical magnitude in 6- to 14-year-old children using a passive functional magnetic resonance imaging adaptation design, thereby mitigating the influence of response selection. A single-digit Arabic numeral was repeatedly presented on a computer screen and interspersed with the presentation of novel digits deviating as a function of numerical ratio (smaller/larger number). Results demonstrated a correlation between age and numerical ratio in the left IPS, suggesting an age-related increase in the extent to which numerical symbols are represented in the left IPS. Brain activation of the right IPS was modulated by numerical ratio but did not correlate with age, indicating hemispheric differences in IPS engagement during the development of symbolic numerical representation

Developmental dyscalculia: compensatory mechanisms in left intraparietal regions in response to nonsymbolic magnitudes

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies investigating the neural mechanisms underlying developmental dyscalculia are scarce and results are thus far inconclusive. Main aim of the present study is to investigate the neural correlates of nonsymbolic number magnitude processing in children with and without dyscalculia. METHODS: 18 children (9 with dyscalculia) were asked to solve a non-symbolic number magnitude comparison task (finger patterns) during brain scanning. For the spatial control task identical stimuli were employed, instructions varying only (judgment of palm rotation). This design enabled us to present identical stimuli with identical visual processing requirements in the experimental and the control task. Moreover, because numerical and spatial processing relies on parietal brain regions, task-specific contrasts are expected to reveal true number-specific activations. RESULTS: Behavioral results during scanning reveal that despite comparable (almost at ceiling) performance levels, task-specific activations were stronger in dyscalculic children in inferior parietal cortices bilaterally (intraparietal sulcus, supramarginal gyrus, extending to left angular gyrus). Interestingly, fMRI signal strengths reflected a group x task interaction: relative to baseline, controls produced significant deactivations in (intra)parietal regions bilaterally in response to number but not spatial processing, while the opposite pattern emerged in dyscalculics. Moreover, beta weights in response to number processing differed significantly between groups in left - but not right - (intra)parietal regions (becoming even positive in dyscalculic children). CONCLUSION: Overall, findings are suggestive of (a) less consistent neural activity in right (intra)parietal regions upon processing nonsymbolic number magnitudes; and (b) compensatory neural activity in left (intra)parietal regions in developmental dyscalculia.(VLID)218888

Common and distinct predictors of non-symbolic and symbolic ordinal number processing across the early primary school years

What are the cognitive mechanisms supporting non-symbolic and symbolic order processing? Preliminary evidence suggests that non-symbolic and symbolic order processing are partly distinct constructs. The precise mechanisms supporting these skills, however, are still unclear. Moreover, predictive patterns may undergo dynamic developmental changes during the first years of formal schooling. This study investigates the contribution of theoretically relevant constructs (non-symbolic and symbolic magnitude comparison, counting and storage and manipulation components of verbal and visuo-spatial working memory) to performance and developmental change in non-symbolic and symbolic numerical order processing. We followed 157 children longitudinally from Grade 1 to 3. In the order judgement tasks, children decided whether or not triplets of dots or digits were arranged in numerically ascending order. Non-symbolic magnitude comparison and visuo-spatial manipulation were significant predictors of initial performance in both non-symbolic and symbolic ordering. In line with our expectations, counting skills contributed additional variance to the prediction of symbolic, but not of non-symbolic ordering. Developmental change in ordering performance from Grade 1 to 2 was predicted by symbolic comparison skills and visuo-spatial manipulation. None of the predictors explained variance in developmental change from Grade 2 to 3. Taken together, the present results provide robust evidence for a general involvement of pair-wise magnitude comparison and visuo-spatial manipulation in numerical ordering, irrespective of the number format. Importantly, counting-based mechanisms appear to be a unique predictor of symbolic ordering. We thus conclude that there is only a partial overlap of the cognitive mechanisms underlying non-symbolic and symbolic order processing

The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis

Purpose This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort.Methods Patients who underwent (68) Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS.Results Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values >= median (p = 0.071), SUVmax values >= 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results.Conclusion The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary

Noninvasive monitoring of myocardial function after surgical and cytostatic therapy in a peritoneal metastasis rat model: assessment with tissue Doppler and non-Doppler 2D strain echocardiography

<p>Abstract</p> <p>Objective</p> <p>We sought to evaluate the impact of different antineoplastic treatment methods on systolic and diastolic myocardial function, and the feasibility estimation of regional deformation parameters with non-Doppler 2D echocardiography in rats.</p> <p>Background</p> <p>The optimal method for quantitative assessment of global and regional ventricular function in rats and the impact of complex oncological multimodal therapy on left- and right-ventricular function in rats remains unclear.</p> <p>Methods</p> <p>90 rats after subperitoneal implantation of syngenetic colonic carcinoma cells underwent different onclogical treatment methods and were diveded into one control group and five treatment groups (with 15 rats in each group): group 1 = control group (without operation and without medication), group 2 = operation group without additional therapy, group 3 = combination of operation and photodynamic therapy, group 4 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with mitomycine, and group 5 = operation in combination with hyperthermic intraoperative peritoneal chemotherapy with gemcitabine, group 6 = operation in combination with taurolidin i.p. instillation. Echocardiographic examination with estimation of wall thickness, diameters, left ventricular fractional shortening, ejection fraction, early and late diastolic transmitral and myocardial velocities, radial and circumferential strain were performed 3–4 days after therapy.</p> <p>Results</p> <p>There was an increase of LVEDD and LVESD in all groups after the follow-up period (P = 0.0037). Other LV dimensions, FS and EF as well as diastolic mitral filling parameters measured by echocardiography were not significantly affected by the different treatments. Values for right ventricular dimensions and function remained unchanged, whereas circumferential 2D strain of the inferior wall was slightly, but significantly reduced under the treatment (-18.1 ± 2.5 before and -16.2 ± 2.9 % after treatment; P = 0.001) without differences between the single treatment groups.</p> <p>Conclusion</p> <p>It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats under different oncological therapy. The deformation was decreased under overall treatment without influence by one specific therapy. Therefore, deformation assessment with non-Doppler 2D strain echocardiography is more sensitive than conventional echocardiography for assessing myocardial dysfunction in rats under oncological treatment.</p

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Classification of 2.4-45.2 Micron Spectra from the ISO Short Wavelength Spectrometer

The Infrared Space Observatory observed over 900 objects with the Short Wavelength Spectrometer in full-grating-scan mode (2.4-45.2 micron). We have developed a comprehensive system of spectral classification using these data. Sources are assigned to groups based on the overall shape of the spectral energy distribution (SED). The groups include naked stars, dusty stars, warm dust shells, cool dust shells, very red sources, and sources with emission lines but no detected continuum. These groups are further divided into subgroups based on spectral features that shape the SED such as silicate or carbon-rich dust emission, silicate absorption, ice absorption, and fine-structure or recombination lines. Caveats regarding the data and data reduction, and biases intrinsic to the database, are discussed. We also examine how the subgroups relate to the evolution of sources to and from the main sequence and how this classification scheme relates to previous systems.Comment: 91 pages (40 for Table 6), 6 figures, accepted by ApJS. Figures 1-5 have degraded resolution due to astro-ph size limits. For full-resolution figures see: http://isc.astro.cornell.edu/~sloan/library/swsclass.html and for the classification table (Table 6) in ASCII format, see: http://isc.astro.cornell.edu/~sloan/library/cat.htm

Positional Cloning of Zinc Finger Domain Transcription Factor Zfp69, a Candidate Gene for Obesity-Associated Diabetes Contributed by Mouse Locus Nidd/SJL

Polygenic type 2 diabetes in mouse models is associated with obesity and results from a combination of adipogenic and diabetogenic alleles. Here we report the identification of a candidate gene for the diabetogenic effect of a QTL (Nidd/SJL, Nidd1) contributed by the SJL, NON, and NZB strains in outcross populations with New Zealand Obese (NZO) mice. A critical interval of distal chromosome 4 (2.1 Mbp) conferring the diabetic phenotype was identified by interval-specific congenic introgression of SJL into diabetes-resistant C57BL/6J, and subsequent reporter cross with NZO. Analysis of the 10 genes in the critical interval by sequencing, qRT–PCR, and RACE–PCR revealed a striking allelic variance of Zfp69 encoding zinc finger domain transcription factor 69. In NZO and C57BL/6J, a retrotransposon (IAPLTR1a) in intron 3 disrupted the gene by formation of a truncated mRNA that lacked the coding sequence for the KRAB (Krüppel-associated box) and Znf-C2H2 domains of Zfp69, whereas the diabetogenic SJL, NON, and NZB alleles generated a normal mRNA. When combined with the B6.V-Lepob background, the diabetogenic Zfp69SJL allele produced hyperglycaemia, reduced gonadal fat, and increased plasma and liver triglycerides. mRNA levels of the human orthologue of Zfp69, ZNF642, were significantly increased in adipose tissue from patients with type 2 diabetes. We conclude that Zfp69 is the most likely candidate for the diabetogenic effect of Nidd/SJL, and that retrotransposon IAPLTR1a contributes substantially to the genetic heterogeneity of mouse strains. Expression of the transcription factor in adipose tissue may play a role in the pathogenesis of type 2 diabetes