A history of the renewal of the corneal epithelium : a 3D animation

Background: To compare the different schemes that have been proposed during the last thirteen years to explain the renewal of the corneal epithelium. Material and Methods:We analyzed all the data present in the literature to explain the renewal of the corneal epithelium in mammals. According to the schemes proposed in the literature we developed a 3D animation to facilitate the understanding of the different concepts. Results:Three different schemes have been proposed to explain the renewal of the corneal epithelium in mammals during the last thirteen years. 1950-1981: the corneal epithelium was thought being renewed by mitosis of cells located in the basal layer. At this time scientist were not talking about stem cells. 1981-1986 was the period of the "XYZ hypothesis" or the transdifferentiation paradigm. At this time the conjunctival epithelium renewed the corneal epithelium in a centripetal migration. 1986-2008: the limbal stem cell paradigm, there were no stem cells in the corneal epithelium, all the corneal stem cells were located in the limbus and renewed the central cornea after a migration of 6 to 7 mm of transient amplifying cells toward the centre of the cornea. 2008, epithelial stem cells were found in the central cornea in mammals (Nature, Majo et al. November 2008). Discussion:We thought that the renewal of the corneal epithelium was completely defined. According to the last results we published in Nature, the current paradigm will be revisited. The experiments we made were on animals and the final demonstration on human has still to be done. If we find the same results in human, a new paradigm will be define and will change the way we consider ocular surface therapy and reconstruction.

3D dose reconstruction for narrow beams using ion chamber array measurements.

3D dose reconstruction is a verification of the delivered absorbed dose. Our aim was to describe and evaluate a 3D dose reconstruction method applied to phantoms in the context of narrow beams. A solid water phantom and a phantom containing a bone-equivalent material were irradiated on a 6 MV linac. The transmitted dose was measured by using one array of a 2D ion chamber detector. The dose reconstruction was obtained by an iterative algorithm. A phantom set-up error and organ interfraction motion were simulated to test the algorithm sensitivity. In all configurations convergence was obtained within three iterations. A local reconstructed dose agreement of at least 3% / 3mm with respect to the planned dose was obtained, except in a few points of the penumbra. The reconstructed primary fluences were consistent with the planned ones, which validates the whole reconstruction process. The results validate our method in a simple geometry and for narrow beams. The method is sensitive to a set-up error of a heterogeneous phantom and interfraction heterogeneous organ motion.

Statistical Modeling of the Eye for Multimodal Treatment Planning for External Beam Radiation Therapy of Intraocular Tumors.

PURPOSE: Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors. METHODS AND MATERIALS: Manual and automatic segmentations were compared for 17 patients, based on head computed tomography (CT) volume scans. A 3D statistical shape model of the cornea, lens, and sclera as well as of the optic disc position was developed. Furthermore, an active shape model was built to enable automatic fitting of the eye model to CT slice stacks. Cross-validation was performed based on leave-one-out tests for all training shapes by measuring dice coefficients and mean segmentation errors between automatic segmentation and manual segmentation by an expert. RESULTS: Cross-validation revealed a dice similarity of 95% ± 2% for the sclera and cornea and 91% ± 2% for the lens. Overall, mean segmentation error was found to be 0.3 ± 0.1 mm. Average segmentation time was 14 ± 2 s on a standard personal computer. CONCLUSIONS: Our results show that the solution presented outperforms state-of-the-art methods in terms of accuracy, reliability, and robustness. Moreover, the eye model shape as well as its variability is learned from a training set rather than by making shape assumptions (eg, as with the spherical or elliptical model). Therefore, the model appears to be capable of modeling nonspherically and nonelliptically shaped eyes.

Improving the Accuracy and Usability of Iowa Falling Weight Deflectometer Data, May 2013

This study aims to improve the accuracy and usability of Iowa Falling Weight Deflectometer (FWD) data by incorporating significant enhancements into the fully-automated software system for rapid processing of the FWD data. These enhancements include: (1) refined prediction of backcalculated pavement layer modulus through deflection basin matching/optimization, (2) temperature correction of backcalculated Hot-Mix Asphalt (HMA) layer modulus, (3) computation of 1993 AASHTO design guide related effective SN (SNeff) and effective k-value (keff ), (4) computation of Iowa DOT asphalt concrete (AC) overlay design related Structural Rating (SR) and kvalue (k), and (5) enhancement of user-friendliness of input and output from the software tool. A high-quality, easy-to-use backcalculation software package, referred to as, I-BACK: the Iowa Pavement Backcalculation Software, was developed to achieve the project goals and requirements. This report presents theoretical background behind the incorporated enhancements as well as guidance on the use of I-BACK developed in this study. The developed tool, I-BACK, provides more fine-tuned ANN pavement backcalculation results by implementation of deflection basin matching optimizer for conventional flexible, full-depth, rigid, and composite pavements. Implementation of this tool within Iowa DOT will facilitate accurate pavement structural evaluation and rehabilitation designs for pavement/asset management purposes. This research has also set the framework for the development of a simplified FWD deflection based HMA overlay design procedure which is one of the recommended areas for future research.

Improving the Accuracy and Usability of Iowa Falling Weight Deflectometer Data: Tech Transfer Summary, May 2013

This study aims to improve the accuracy and usability of Iowa Falling Weight Deflectometer (FWD) data by incorporating significant enhancements into the fully-automated software system for rapid processing of the FWD data. These enhancements include: (1) refined prediction of backcalculated pavement layer modulus through deflection basin matching/optimization, (2) temperature correction of backcalculated Hot-Mix Asphalt (HMA) layer modulus, (3) computation of 1993 AASHTO design guide related effective SN (SNeff) and effective k-value (keff ), (4) computation of Iowa DOT asphalt concrete (AC) overlay design related Structural Rating (SR) and kvalue (k), and (5) enhancement of user-friendliness of input and output from the software tool. A high-quality, easy-to-use backcalculation software package, referred to as, I-BACK: the Iowa Pavement Backcalculation Software, was developed to achieve the project goals and requirements. This report presents theoretical background behind the incorporated enhancements as well as guidance on the use of I-BACK developed in this study. The developed tool, I-BACK, provides more fine-tuned ANN pavement backcalculation results by implementation of deflection basin matching optimizer for conventional flexible, full-depth, rigid, and composite pavements. Implementation of this tool within Iowa DOT will facilitate accurate pavement structural evaluation and rehabilitation designs for pavement/asset management purposes. This research has also set the framework for the development of a simplified FWD deflection based HMA overlay design procedure which is one of the recommended areas for future research.

Accuracy of plant assemblage predictions from species distribution models varies along environmental gradients

Aim: Climatic niche modelling of species and community distributions implicitly assumes strong and constant climatic determinism across geographic space. This assumption had however never been tested so far. We tested it by assessing how stacked-species distribution models (S-SDMs) perform for predicting plant species assemblages along elevation. Location: Western Swiss Alps. Methods: Using robust presence-absence data, we first assessed the ability of topo-climatic S-SDMs to predict plant assemblages in a study area encompassing a 2800 m wide elevation gradient. We then assessed the relationships among several evaluation metrics and trait-based tests of community assembly rules. Results: The standard errors of individual SDMs decreased significantly towards higher elevations. Overall, the S-SDM overpredicted far more than they underpredicted richness and could not reproduce the humpback curve along elevation. Overprediction was greater at low and mid-range elevations in absolute values but greater at high elevations when standardised by the actual richness. Looking at species composition, the evaluation metrics accounting for both the presence and absence of species (overall prediction success and kappa) or focusing on correctly predicted absences (specificity) increased with increasing elevation, while the metrics focusing on correctly predicted presences (Jaccard index and sensitivity) decreased. The best overall evaluation - as driven by specificity - occurred at high elevation where species assemblages were shown to be under significant environmental filtering of small plants. In contrast, the decreased overall accuracy in the lowlands was associated with functional patterns representing any type of assembly rule (environmental filtering, limiting similarity or null assembly). Main Conclusions: Our study reveals interesting patterns of change in S-SDM errors with changes in assembly rules along elevation. Yet, significant levels of assemblage prediction errors occurred throughout the gradient, calling for further improvement of SDMs, e.g., by adding key environmental filters that act at fine scales and developing approaches to account for variations in the influence of predictors along environmental gradients.

Axial sub-nanometer accuracy in digital holographic microscopy

We present state-of-the-art dual-wavelength digital holographic microscopy (DHM) measurement on a calibrated 8.9 nm high chromium thin step sample and demonstrate sub-nanometer axial accuracy. By using a modified DHM reference calibrated hologram (RCH) reconstruction method, a temporal averaging procedure and a specific dual-wavelength DHM arrangement, it is shown that specimen topography can be measured with an accuracy, defined as the axial standard deviation, reduced to at least 0.9 nm. Indeed for the first time to the best of our knowledge, it is reported that averaging each of the two wavefronts recorded with real-time dual-wavelength DHM can provide up to 30% spatial noise reduction for the given configuration. Moreover, the presented experimental configuration achieves a temporal stability below 0.8 nm, thus paving the way to Angström range for dual-wavelength DHM.

Flow targeted 3D steady-state free-precession coronary MR angiography: comparison of three different imaging approaches.

PURPOSE: To compare 3 different flow targeted magnetization preparation strategies for coronary MR angiography (cMRA), which allow selective visualization of the vessel lumen. MATERIAL AND METHODS: The right coronary artery of 10 healthy subjects was investigated on a 1.5 Tesla MR system (Gyroscan ACS-NT, Philips Healthcare, Best, NL). A navigator-gated and ECG-triggered 3D radial steady-state free-precession (SSFP) cMRA sequence with 3 different magnetization preparation schemes was performed referred to as projection SSFP (selective labeling of the aorta, subtraction of 2 data sets), LoReIn SSFP (double-inversion preparation, selective labeling of the aorta, 1 data set), and inflow SSFP (inversion preparation, selective labeling of the coronary artery, 1 data set). Signal-to-noise ratio (SNR) of the coronary artery and aorta, contrast-to-noise ratio (CNR) between the coronary artery and epicardial fat, vessel length and vessel sharpness were analyzed. RESULTS: All cMRA sequences were successfully obtained in all subjects. Both projection SSFP and LoReIn SSFP allowed for selective visualization of the coronary arteries with excellent background suppression. Scan time was doubled in projection SSFP because of the need for subtraction of 2 data sets. In inflow SSFP, background suppression was limited to the tissue included in the inversion volume. Projection SSFP (SNR(coro): 25.6 +/- 12.1; SNR(ao): 26.1 +/- 16.8; CNR(coro-fat): 22.0 +/- 11.7) and inflow SSFP (SNR(coro): 27.9 +/- 5.4; SNR(ao): 37.4 +/- 9.2; CNR(coro-fat): 24.9 +/- 4.8) yielded significantly increased SNR and CNR compared with LoReIn SSFP (SNR(coro): 12.3 +/- 5.4; SNR(ao): 11.8 +/- 5.8; CNR(coro-fat): 9.8 +/- 5.5; P < 0.05 for both). Longest visible vessel length was found with projection SSFP (79.5 mm +/- 18.9; P < 0.05 vs. LoReIn) whereas vessel sharpness was best in inflow SSFP (68.2% +/- 4.5%; P < 0.05 vs. LoReIn). Consistently good image quality was achieved using inflow SSFP likely because of the simple planning procedure and short scanning time. CONCLUSION: Three flow targeted cMRA approaches are presented, which provide selective visualization of the coronary vessel lumen and in addition blood flow information without the need of contrast agent administration. Inflow SSFP yielded highest SNR, CNR and vessel sharpness and may prove useful as a fast and efficient approach for assessing proximal and mid vessel coronary blood flow, whereas requiring less planning skills than projection SSFP or LoReIn SSFP.

Accuracy of four cardiovascular risk scores in a Swiss population-based cohort

Purpose: To assess the global cardiovascular (CV) risk of an individual, several scores have been developed. However, their accuracy and comparability need to be evaluated in populations others from which they were derived. The aim of this study was to compare the predictive accuracy of 4 CV risk scores using data of a large population-based cohort. Methods: Prospective cohort study including 4980 participants (2698 women, mean age± SD: 52.7±10.8 years) in Lausanne, Switzerland followed for an average of 5.5 years (range 0.2 - 8.5). Two end points were assessed: 1) coronary heart disease (CHD), and 2) CV diseases (CVD). Four risk scores were compared: original and recalibrated Framingham coronary heart disease scores (1998 and 2001); original PROCAM score (2002) and its recalibrated version for Switzerland (IAS-AGLA); Reynolds risk score. Discrimination was assessed using Harrell's C statistics, model fitness using Akaike's information criterion (AIC) and calibration using pseudo Hosmer-Lemeshow test. The sensitivity, specificity and corresponding 95% confidence intervals were assessed for each risk score using the highest risk category ([20+ % at 10 years) as the "positive" test. Results: Recalibrated and original 1998 and original 2001 Framingham scores show better discrimination (>0.720) and model fitness (low AIC) for CHD and CVD. All 4 scores are correctly calibrated (Chi2<20). The recalibrated Framingham 1998 score has the best sensitivities, 37.8% and 40.4%, for CHD and CVD, respectively. All scores present specificities >90%. Framingham 1998, PROCAM and IAS-AGLA scores include the greatest proportion of subjects (>200) in the high risk category whereas recalibrated Framingham 2001 and Reynolds include <=44 subjects. Conclusion: In this cohort, we see variations of accuracy between risk scores, the original Framingham 2001 score demonstrating the best compromise between its accuracy and its limited selection of subjects in the highest risk category. We advocate that national guidelines, based on independently validated data, take into account calibrated CV risk scores for their respective countries.

SIMSAFADIM-CLASTIC: A new approach to mathematical 3D forward simulation modelling for terrigenous and carbonate marine sedimentation

Most sedimentary modelling programs developed in recent years focus on either terrigenous or carbonate marine sedimentation. Nevertheless, only a few programs have attempted to consider mixed terrigenous-carbonate sedimentation, and most of these are two-dimensional, which is a major restriction since geological processes take place in 3D. This paper presents the basic concepts of a new 3D mathematical forward simulation model for clastic sediments, which was developed from SIMSAFADIM, a previous 3D carbonate sedimentation model. The new extended model, SIMSAFADIM-CLASTIC, simulates processes of autochthonous marine carbonate production and accumulation, together with clastic transport and sedimentation in three dimensions of both carbonate and terrigenous sediments. Other models and modelling strategies may also provide realistic and efficient tools for prediction of stratigraphic architecture and facies distribution of sedimentary deposits. However, SIMSAFADIM-CLASTIC becomes an innovative model that attempts to simulate different sediment types using a process-based approach, therefore being a useful tool for 3D prediction of stratigraphic architecture and facies distribution in sedimentary basins. This model is applied to the neogene Vallès-Penedès half-graben (western Mediterranean, NE Spain) to show the capacity of the program when applied to a realistic geologic situation involving interactions between terrigenous clastics and carbonate sediments.

Free-breathing 3D steady-state free precession coronary MR angiography with radial k-space sampling: comparison with cartesian k-space sampling and cartesian gradient-echo coronary MR angiography--pilot study.

The authors compared radial steady-state free precession (SSFP) coronary magnetic resonance (MR) angiography, cartesian k-space sampling SSFP coronary MR angiography, and gradient-echo coronary MR angiography in 16 healthy adults and four pilot study patients. Standard gradient-echo MR imaging with a T2 preparatory pulse and cartesian k-space sampling was the reference technique. Image quality was compared by using subjective motion artifact level and objective contrast-to-noise ratio and vessel sharpness. Radial SSFP, compared with cartesian SSFP and gradient-echo MR angiography, resulted in reduced motion artifacts and superior vessel sharpness. Cartesian SSFP resulted in increased motion artifacts (P <.05). Contrast-to-noise ratio with radial SSFP was lower than that with cartesian SSFP and similar to that with the reference technique. Radial SSFP coronary MR angiography appears preferable because of improved definition of vessel borders.

Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation.

OBJECTIVES: To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort. METHODS: This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm(2)). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method. RESULTS: Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 - 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 - 0.82); high specificities (range, 0.64 - 1) and negative predictive values (range, 0.81 - 0.97) were confirmed. CONCLUSION: HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion. KEY POINTS: • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.