Diversity and genetic architecture of agro-morphological traits in a core collection of European traditional tomato.

European traditional tomato varieties have been selected by farmers given their consistent performance and adaptation to local growing conditions. Here we developed a multipurpose core collection, comprising 226 accessions representative of the genotypic, phenotypic, and geographical diversity present in European traditional tomatoes, to investigate the basis of their phenotypic variation, gene×environment interactions, and stability for 33 agro-morphological traits. Comparison of the traditional varieties with a modern reference panel revealed that some traditional varieties displayed excellent agronomic performance and high trait stability, as good as or better than that of their modern counterparts. We conducted genome-wide association and genome-wide environment interaction studies and detected 141 quantitative trait loci (QTLs). Out of those, 47 QTLs were associated with the phenotype mean (meanQTLs), 41 with stability (stbQTLs), and 53 QTL-by-environment interactions (QTIs). Most QTLs displayed additive gene actions, with the exception of stbQTLs, which were mostly recessive and overdominant QTLs. Both common and specific loci controlled the phenotype mean and stability variation in traditional tomato; however, a larger proportion of specific QTLs was observed, indicating that the stability gene regulatory model is the predominant one. Developmental genes tended to map close to meanQTLs, while genes involved in stress response, hormone metabolism, and signalling were found within regions affecting stability. A total of 137 marker-trait associations for phenotypic means and stability were novel, and therefore our study enhances the understanding of the genetic basis of valuable agronomic traits and opens up a new avenue for an exploitation of the allelic diversity available within European traditional tomato germplasm.

Atlas of phenotypic, genotypic and geographical diversity present in the European traditional tomato.

The Mediterranean basin countries are considered secondary centres of tomato diversification. However, information on phenotypic and allelic variation of local tomato materials is still limited. Here we report on the evaluation of the largest traditional tomato collection, which includes 1499 accessions from Southern Europe. Analyses of 70 traits revealed a broad range of phenotypic variability with different distributions among countries, with the culinary end use within each country being the main driver of tomato diversification. Furthermore, eight main tomato types (phenoclusters) were defined by integrating phenotypic data, country of origin, and end use. Genome-wide association study (GWAS) meta-analyses identified associations in 211 loci, 159 of which were novel. The multidimensional integration of phenoclusters and the GWAS meta-analysis identified the molecular signatures for each traditional tomato type and indicated that signatures originated from differential combinations of loci, which in some cases converged in the same tomato phenotype. Our results provide a roadmap for studying and exploiting this untapped tomato diversity.

European traditional tomatoes galore: a result of farmers' selection of a few diversity-rich loci.

A comprehensive collection of 1254 tomato accessions, corresponding to European traditional and modern varieties, early domesticated varieties, and wild relatives, was analyzed by genotyping by sequencing. A continuous genetic gradient between the traditional and modern varieties was observed. European traditional tomatoes displayed very low genetic diversity, with only 298 polymorphic loci (95% threshold) out of 64 943 total variants. European traditional tomatoes could be classified into several genetic groups. Two main clusters consisting of Spanish and Italian accessions showed higher genetic diversity than the remaining varieties, suggesting that these regions might be independent secondary centers of diversity with a different history. Other varieties seem to be the result of a more recent complex pattern of migrations and hybridizations among the European regions. Several polymorphic loci were associated in a genome-wide association study with fruit morphological traits in the European traditional collection. The corresponding alleles were found to contribute to the distinctive phenotypic characteristic of the genetic varietal groups. The few highly polymorphic loci associated with morphological traits in an otherwise a low-diversity population suggests a history of balancing selection, in which tomato farmers likely maintained the morphological variation by inadvertently applying a high selective pressure within different varietal types.

Phenotypic diversity and distinctiveness of the Belltall garlic landrace.

Among the Mediterranean horticultural landraces, garlic is one of the crops most threatened by genetic erosion. Due to its sexual sterility and to the incidence of seed-borne diseases, historical varieties have been widely replaced by commercial cultivars. In Catalonia, despite the historical relevance of the crop, solely the Belltall garlic landrace is cultivated for commercial purposes. To assess the genotypic and phenotypic diversity within the Belltall garlic, we evaluated sixteen local accessions and five recognized traditional and modern varieties as controls. Genetic analysis with SSR and InDel markers showed low genetic diversity within the Belltall population, grouping modern and traditional varieties separately. Farmers and consumers were involved in the definition of the landrace ideotype and classified the materials by means of projective mapping. Scant phenotypic diversity was found within the Belltall landrace, which is characterized by its color profile and the small size of bulb and cloves. The Belltall landrace grown outside its area of origin lost the distinctive quality signals that differentiate the landrace from the commercial cultivars (clove appearance), indicating that the high quality of the landrace is under genotype-by-environment effects (i.e. local adaptation). Moreover, the size of the Belltall sowing clove had a strong effect on the harvested bulb size. Our research represents a case study for the description of the variability within garlic landraces and an approach to quantify the phenomenon of local adaptation that currently drives their conservation.

Sensory Traits and Consumer's Perceived Quality of Traditional and Modern Fresh Market Tomato Varieties: A Study in Three European Countries.

Consumer dissatisfaction with the flavor quality of many modern fresh market tomato varieties has fostered breeders' interest in sensory quality improvement, and the demand for traditional varieties, which are generally associated with better flavor. To achieve further knowledge on the factors influencing the sensory quality and consumers' preferences and perception, European traditional and modern fresh market tomato varieties were grown and evaluated in France, Italy, and Spain. Different growing conditions were tested in France (soilless vs. soil) and in Spain (open field vs. greenhouse), while in Italy fruits were evaluated at two ripening stages. Fruit quality was assessed by integrating physicochemical analyses, sensory profiles, and consumer tests. In all three countries, overall modern varieties were perceived as having more intense "tomato flavor" and "overall flavor" than traditional ones. In France and Spain, consumers' preferences were more oriented towards modern varieties than traditional ones. Significant growing condition effects were found on sensory and physicochemical traits, while the effect on consumers' overall liking was not significant, largely depending on the genotype. A fair agreement between product configurations from descriptive analysis by trained assessors and Check-All-That-Apply (CATA) questions by consumers was observed. Penalty-lift analysis based on CATA allowed identifying positive and negative drivers of liking.

Nutritional values of raw and cooked 'calçots' (Allium cepa L. resprouts), an expanding crop.

BACKGROUND: 'Calçot' is the Catalan name for the immature floral stems of second-year onion resprouts of the Blanca Tardana de Lleida (BTL) landrace. Highly appreciated for their sensory attributes, these resprouts are typically consumed after roasting on an open fire. Now new preparations are appearing, helping to expand the market for 'calçots'. This study aimed (i) to compare the nutritional and sensory characteristics of BTL 'calçots' versus other onion varieties; (ii) to analyze the effects of cooking and / or in vitro gastrointestinal digestion on the nutritional properties of 'calçots'; and (iii) to determine the influence of the environment on the antioxidant properties of 'calçots'. RESULTS: The nutritional and sensory characteristics of both raw and cooked 'calçots' differed between varieties, with the exception of some minerals. Flavonoid content decreased by 85% during cooking, and total phenolic content decreased by 30%. By contrast, antioxidant activity increased after cooking. Most traits had a nonlinear response to heating, and differences between varieties generally decreased after cooking. Location also had a strong effect on antioxidant activity. In vitro digestion of cooked 'calçots' sharply decreased antioxidant activity after the intestinal phase. The only significant genotypic correlation between sensory and nutritional quality was the correlation between sweetness and ash content (R = -0.97). CONCLUSION: Cooked BTL 'calçots' are within the limits of the onion domain for nutritional properties, and the variability reported for onion bulbs is also present in resprouts. The effects of the environment, cooking, and in vitro digestion clearly overlap the genetic effects. © 2019 Society of Chemical Industry.

Evaluation of a novel software application for magnetic resonance distortion correction in cranial stereotactic radiosurgery.

This study aimed to validate a novel commercially available software for correcting spatial distortion in cranial magnetic resonance (MR) images. This software has been used to assess the dosimetric impact of MR distortion in stereotactic radiosurgery (SRS) treatments of vestibular schwannomas (VSs). Five MR datasets were intentionally distorted. Each distorted MR dataset was corrected using the Cranial Distortion software, obtaining a new corrected MR dataset (MRcorr). The accuracy of the correction was quantified by calculating the target registration error (TRE) for 6 anatomical landmarks identified in the co-registered MRcorr and planning computed tomography (pCT) images. Nine VS cases were included to investigate the impact of the MR distortion in SRS plans. Each SRS plan was calculated on the pCT (1 × 1 × 1 mm3 voxel) with the target and organs at risk (OARs) delineated using the planning MR dataset. This MR dataset was then corrected (MRcorr) using the Cranial Distortion software. Geometrical agreement between the original target and the corresponding corrected target was assessed using several metrics: MacDonald criteria, mean distance to agreement (MDA), and Dice similarity coefficient (DSC). Target coverage (D99%) and maximum doses (D2%) to ipsilateral cochlea and brainstem resulting on the MRcorr dataset were compared with the original values. TRE values (0.6 mm ± 0.3 mm) and differences found in Macdonald criteria (0.3 mm ± 0.4 mm and 0.3 mm ± 0.3 mm) and MDA (0.8 mm ± 0.2 mm) were mostly within the voxel size dimension of the pCT scan (1 × 1 × 1 mm3). High similarity (DSC > 0.7) between the original and corrected targets was found. Small dose differences for the original and corrected structures were found: 0.1 Gy ± 0.1 Gy for target D99%, 0.2 Gy ± 0.3 Gy for cochlea D2%, and 0.1 Gy ± 0.1 Gy for brainstem D2%. Our study shows that Distortion Correction software can be a helpful tool to detect and adequately correct brain MR distortions. However, a negligible dosimetric impact of MR distortion has been detected in our clinical practice.

Plant Genebanks: Present Situation and Proposals for Their Improvement. the Case of the Spanish Network.

Genebanks were created by the middle of the twentieth century to preserve cultivated biodiversity when landraces began to be substituted by modern varieties. This move was generally accepted as a necessary step to safeguard the future. After about 75 years of collecting and maintaining genetic resources, the increasing ability of biotechnology to create new variability brings the roles of genebanks in the present and near future into question. As a continuation of several workshops that started in 2014, staff of some representative genebanks have met to discuss how the Spanish Plant Genetic Resources Network can be improved, identifying the following major shortcomings: lack of efficient coordination in the distribution of species among genebanks; too many genebanks; existence of detected and undetected duplicates; insufficient rate of regeneration; insufficient phenotyping, genotyping, and epiphenotyping; unsatisfactory rate of use by end users; and, insufficient funding. As a considerable increase in public funding is unlikely, we propose some strategies to increase the efficiency of the system. The most urgent tasks are to strengthen the rationalization of the network by establishing a clear hierarchy and functions, to improve the information in the base collection by deep characterization including not only phenotypes but also uses and utilities, to progressively replace the active collections with focused core collections constructed to meet users' needs, to optimize regeneration protocols, to limit new collecting expeditions of Spanish crop wild relatives to those growing in threatened habitats, and to develop user-friendly platforms to access germplasm documentation, including a unified system of descriptors and classification categories. Current advances in biotechnology, and especially those in gene editing will have without doubt an impact on the role of genebanks. However, the high number of genes and gene combinations created by evolution they hold cannot be produced by these techniques at present. So, these reservoirs of variability will continue to be indispensable for the near-medium future while the function of all the genes is unveiled. In turn, biotechnologies and gene editing will allow us to take advantage of the information held in genebanks in a more efficient and fast way, contributing to a better rationalization and functioning.

The Spanish Core Collection of Common Beans (Phaseolus vulgaris L.): An Important Source of Variability for Breeding Chemical Composition.

The Iberian Peninsula is considered as a secondary center of diversity for the common bean, and the Spanish National Plant Genetic Resources Centre's germplasm bank holds more than 3,000 Spanish accessions of Phaseolus vulgaris L. from which a core collection of 202 landraces has been selected. In order to encourage the use of this abundant resource, this study aimed to characterize genetic diversity, by measuring chemical composition in these core collections (in both the seed coat and cotyledon) using previously developed near infrared spectroscopy models. Crucially, these landraces in question all originated under similar agroclimatic conditions, allowing these field trials to be conducted in a single location without significantly altering the agronomic behavior of individual accessions. Using previously reported data, we also explored the correlations between chemical composition and culinary/sensory traits, as well as possible associations between chemical composition and seed coat color or gene pool (Middle American or Andean). The general Mahalanobis distance was >3 in only 11 of 1,950 estimations, confirming the robustness of the regression models previously developed. Variability was greater in seed coat than in cotyledon compounds and ranges for all compounds were wide: ash 34-94 g/kg, Ca 5-31 g/kg, dietary fiber 554-911 g/kg, Mg 2-4.4 g/kg, uronic acid 95-155 g/kg, protein 192-304 g/kg, starch 339-446 g/kg, amylose 208-291 g/kg, amylopectin 333-482 g/kg, and apparent amylose 241-332 g/kg. Accessions with white seed coats tended to be richer in ash, dietary fiber, uronic acid, and Ca, and accessions of the Middle American gene pool had on average 65% more Ca than the Andean gene pool. Strong genetic correlations were not identified between chemical and culinary/sensory traits. This is particularly positive with regards to plant breeding, as it means that synchronic improvement of nutritional composition and sensory traits is possible. The genetic diversity of chemical composition described in the Spanish core collection of beans therefore represents a promising opportunity to develop cultivars with superior nutritional profiles.

Improving the Commercial Value of the 'Calçot' (Allium cepa L.) Landrace: Influence of Genetic and Environmental Factors in Chemical Composition and Sensory Attributes.

Landraces are considered valuable for their close ties to local cultures, adaptation to low inputs, and quality. 'Calçots' are the immature floral stems of second-year sprouts of onions from the 'Blanca Tardana de Lleida' landrace. 'Calçots' grown in their traditional area of cultivation have been awarded Protected Geographic Indication (PGI) 'Calçot de Valls' from the European Union. Despite annual sales of about €15 million, 'calçot' germplasm and cultivation methods are under-researched. This study aimed to estimate the influence of genetic and environmental factors in the chemical and sensory characteristics of 'calçots' to enable strategies to improve their commercial value to be devised. To this end, we tested the landrace and three new, more productive varieties derived from the landrace in experiments conducted over two seasons in six locations (within and outside the PGI zone), using two planting dates and two harvesting times. The results point to a major environmental influence in the quality of 'calçots.' The analysis of variance found all factors related with environmental influence were significant in most chemical traits considered (dry matter content, soluble solids content, pH, titratable acidity, and ash content), while the variety factor was significant only for titratable acidity. In sensory analyses, the variety factor and all the environmental factors had significant effects in all sensory traits recorded (sweetness, fiber perception, and off-flavors). In both chemical and sensory traits, most significant interactions involved the environmental factors. The negative correlation found between sweetness and fiber perception and off-flavors suggests that additional selection can bring 'calçots' closer to the sensory ideotype. Although clearly more productive, the new 'calçot' varieties maintain the chemical composition and sensory value of the landrace. Thus, fine-tuning the cultivation and/or breeding of the landrace for both yield and quality seem viable approaches to obtaining better commercial products.

Determination of chemical properties in 'calçot' (Allium cepa L.) by near infrared spectroscopy and multivariate calibration.

'Calçots', the immature floral stems of second-year onion resprouts, are an economically important traditional crop in Catalonia (Spain). Classical approaches to evaluating the chemical properties of 'calçots' are time consuming and expensive; near-infrared spectroscopy (NIRS) may be faster and cheaper. We used NIRS to develop partial least square (PLS) models to predict dry matter, soluble solid content, titratable acidity, and ash content in cooked 'calçots'. To guarantee the robustness of the models, calibration samples were grown and analyzed in a first season (2014-15) and validation samples in a second season (2015-16). NIRS on puree spectra estimated dry matter and soluble solid content with excellent accuracy (R2pred = 0.953, 0.985 and RPD = 4.571, 8.068, respectively). However, good estimation of titratable acidity and ash content required using ground dried puree spectra (R2pred = 0.852, 0.820 and RPD = 2.590, 1.987, respectively). NIRS can be a helpful tool for 'calçots' breeding and quality control.

Fast protocol for radiochromic film dosimetry using a cloud computing web application.

PURPOSE: To investigate the feasibility of a fast protocol for radiochromic film dosimetry to verify intensity-modulated radiotherapy (IMRT) plans. METHOD AND MATERIALS: EBT3 film dosimetry was conducted in this study using the triple-channel method implemented in the cloud computing application (Radiochromic.com). We described a fast protocol for radiochromic film dosimetry to obtain measurement results within 1h. Ten IMRT plans were delivered to evaluate the feasibility of the fast protocol. The dose distribution of the verification film was derived at 15, 30, 45min using the fast protocol and also at 24h after completing the irradiation. The four dose maps obtained per plan were compared using global and local gamma index (5%/3mm) with the calculated one by the treatment planning system. Gamma passing rates obtained for 15, 30 and 45min post-exposure were compared with those obtained after 24h. RESULTS: Small differences respect to the 24h protocol were found in the gamma passing rates obtained for films digitized at 15min (global: 99.6%±0.9% vs. 99.7%±0.5%; local: 96.3%±3.4% vs. 96.3%±3.8%), at 30min (global: 99.5%±0.9% vs. 99.7%±0.5%; local: 96.5%±3.2% vs. 96.3±3.8%) and at 45min (global: 99.2%±1.5% vs. 99.7%±0.5%; local: 96.1%±3.8% vs. 96.3±3.8%). CONCLUSIONS: The fast protocol permits dosimetric results within 1h when IMRT plans are verified, with similar results as those reported by the standard 24h protocol.

Toward an Evolved Concept of Landrace.

The term "landrace" has generally been defined as a cultivated, genetically heterogeneous variety that has evolved in a certain ecogeographical area and is therefore adapted to the edaphic and climatic conditions and to its traditional management and uses. Despite being considered by many to be inalterable, landraces have been and are in a constant state of evolution as a result of natural and artificial selection. Many landraces have disappeared from cultivation but are preserved in gene banks. Using modern selection and breeding technology tools to shape these preserved landraces together with the ones that are still cultivated is a further step in their evolution in order to preserve their agricultural significance. Adapting historical landraces to present agricultural conditions using cutting-edge breeding technology represents a challenging opportunity to use them in a modern sustainable agriculture, as an immediate return on the investment is highly unlikely. Consequently, we propose a more inclusive definition of landraces, namely that they consist of cultivated varieties that have evolved and may continue evolving, using conventional or modern breeding techniques, in traditional or new agricultural environments within a defined ecogeographical area and under the influence of the local human culture. This includes adaptation of landraces to new management systems and the unconscious or conscious selection made by farmers or breeders using available technology. In this respect, a mixed selection system might be established in which farmers and other social agents develop evolved landraces from the variability generated by public entities.

Dosimetric feasibility of an "off-breast isocenter" technique for whole-breast cancer radiotherapy.

AIM: To investigate the viability of placing the treatment isocenter at the patient midline for breast cancer radiotherapy in order to avoid the risk of collisions during image-guided setup and treatment delivery. BACKGROUND: The use of kilovoltage orthogonal setup images has spread in last years in breast radiotherapy. There is a potential risk of an imaging system-patient collision when the isocenter is laterally placed. MATERIALS AND METHODS: Twenty IMRT plans designed by placing the isocenter within the breast volume ("plan_ref"), were retrospectively replanned by shifting the isocenter at the patient's midline ("plan_off-breast"). An integrated simultaneous boost (SIB) technique was used. Multiple metrics for the planning target volumes (PTVs) and organs at risk (OARs) were compared for both approaches using a paired t test. RESULTS: Comparing plan_ref vs. plan_off-breast, no significant differences in PTV coverage (V95%) were found (96.5% vs. 96.2%; p = 0.361 to PTVbreast; 97.0% vs. 97.0%; p = 0.977 to PTVtumor_bed). With regard to OARs, no substantial differences were observed in any analyzed metric: V5Gy (30.3% vs. 31.4%; p = 0.486), V20Gy (10.3% vs. 10.3%; p = 0.903) and mean dose (7.1 Gy vs. 7.1 Gy; p = 0.924) to the ipsilateral lung; V5Gy (11.2% vs. 10.0%; p = 0.459), V30Gy (0.7% vs. 0.6%; p = 0.251) and mean dose (2.3 Gy vs. 2.2 Gy; p = 0.400) to the heart; and average dose to the contralateral breast (0.4 Gy vs. 0.5 Gy; p = 0.107). CONCLUSIONS: The off-breast isocenter solution resulted in dosimetrically comparable plans as the reference technique, avoiding the collision risk during the treatment session.

Dosimetric comparison of intensity modulated radiosurgery with dynamic conformal arc radiosurgery for small cranial lesions.

AIMS: To dosimetrically compare the fixed gantry intensity modulated radiosurgery (IMRS) with dynamic conformal arc radiosurgery (DCARS) for cranial lesions. This study investigates whether IMRS can be an adequate dosimetric alternative to DCARS for cranial stereotactic radiosurgery (SRS). SUBJECTS AND METHODS: Forty-five SRS procedures for solitary brain metastasis (range: 0.44-29.18 cm 3) performed at our institution were selected for this study. Two plans were generated per patient: One IMRS plan using a multileaf collimation (MLC) of 5 mm, and one DCARS plan designed with a 3 mm micro-MLC. Dosimetric comparison metrics include the target coverage (Cov), conformity index (CI), homogeneity index (HI), gradient index (GI), and volume of the normal brain tissue receiving ≥12 Gy (V12). In addition, maximum doses to organs at risk (OAR) (brainstem, optic apparatus and cochlea) were compared for both techniques. RESULTS: Compared to DCARS, IMRS improved mean CI (IMRS: 0.81 vs. DCARS: 0.63, P < 0.001), with no significant difference in target Cov (IMRS: 0.99 vs. DCARS: 0.99, P > 0.05), HI (IMRS: 1.22 vs. DCARS: 1.24, P > 0.05), GI (IMRS: 5.44 vs. DACRS: 5.44, P > 0.05). A weak significant difference in V12 (IMRS: 4.6 cm 3 vs. 5.2 cm 3, P = 0.033) was obtained. Subgroup analysis per target volume (small: <1 cm 3, intermediate: ≤1 cm 3 and <5 cm 3 and large: ≥5 cm 3) only revealed the statistically difference for CI metric (P < 0.001). No significant differences were found for maximum dose to the OAR. CONCLUSIONS: We have shown that IMRS provides the dosimetric advantages compared with DCARS. Based on the dosimetric findings in this study, fixed gantry IMRS technique can be adopted as a standard procedure for cranial SRS when micro-MLC technology is not available on the linear accelerator.

Evaluation of the setup margins for cone beam computed tomography-guided cranial radiosurgery: A phantom study.

The aim of this study is to evaluate the setup margins from the clinical target volume (CTV) to planning target volume (PTV) for cranial stereotactic radiosurgery (SRS) treatments guided by cone beam computed tomography (CBCT). We designed an end-to-end (E2E) test using a skull phantom with an embedded 6mm tungsten ball (target). A noncoplanar plan was computed (E2E plan) to irradiate the target. The CBCT-guided positioning of the skull phantom on the linac was performed. Megavoltage portal images were acquired after 15 independent deliveries of the E2E plan. The displacement 2-dimensional (2D) vector between the centers of the square field and the ball target on each portal image was used to quantify the isocenter accuracy. Geometrical margins on each patient׳s direction (left-right or LR, anterior-posterior or AP, superior-inferior or SI) were calculated. Dosimetric validation of the margins was performed in 5 real SRS cases: 3-dimesional (3D) isocenter deviations were mimicked, and changes in CTV dose coverage and organs-at-risk (OARs) dosage were analyzed. The CTV-PTV margins of 1.1mm in LR direction, and 0.7mm in AP and SI directions were derived from the E2E tests. The dosimetric analysis revealed that a 1-mm uniform margin was sufficient to ensure the CTV dose coverage, without compromising the OAR dose tolerances. The effect of isocenter uncertainty has been estimated to be 1mm in our CBCT-guided SRS approach.

Dosimetric feasibility of an "off-target isocenter" technique for cranial intensity-modulated radiosurgery.

To evaluate the dosimetric effect of placing the isocenter away from the planning target volume (PTV) on intensity-modulated radiosurgery (IMRS) plans to treat brain lesions. A total of 15 patients who received cranial IMRS at our institution were randomly selected. Each patient was treated with an IMRS plan designed with the isocenter located at the target center (plan A). A second off-target isocenter plan (plan B) was generated for each case. In all the plans,100% of the prescription dose covered 99% of the target volume. The plans A and B were compared for the target dosage (conformity index [CI] and homogeneity index) and organs-at-risk (OAR) dose sparing. Peripheral dose falloff was compared by using the metrics volume of normal brain receiving more than 12-Gy dose (V12) and CI at the level of the 50% of the prescription dose (CI 50%). The values found for each metric (plan B vs plan A) were (mean ± standard deviation [SD]) as follows-CI: 1.28 ± 0.15 vs 1.28 ± 0.15, p = 0.978; homogeneity index (HI): 1.29 ± 0.14 vs 1.34 ± 0.17, p = 0.079; maximum dose to the brainstem: 2.95 ± 2.11 vs 2.89 ± 1.88Gy, p = 0.813; maximum dose to the optical pathway: 2.65 ± 4.18 vs 2.44 ± 4.03Gy, p = 0.195; and maximum dose to the eye lens: 0.33 ± 0.73 vs 0.33 ± 0.53Gy, p = 0.970. The values of the peripheral dose falloff were (plan B vs plan A) as follows-V12: 5.98 ± 4.95 vs 6.06 ± 4.92cm(3), p = 0.622, and CI 50%: 6.08 ± 2.77 vs 6.28 ± 3.01, p = 0.119. The off-target isocenter solution resulted in dosimetrically comparable plans as the center-target isocenter technique, by avoiding the risk of gantry-couch collision during the cone beam computed tomography (CBCT) acquisition.

A dosimetric evaluation of the Eclipse AAA algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery.

The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [AAA]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1cc) were planned (Eclipse, AAA, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2D dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46mm. According to our results, we conclude that the Eclipse/AAA algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.

Feasibility of an online adaptive replanning method for cranial frameless intensity-modulated radiosurgery.

To introduce an approach for online adaptive replanning (i.e., dose-guided radiosurgery) in frameless stereotactic radiosurgery, when a 6-dimensional (6D) robotic couch is not available in the linear accelerator (linac). Cranial radiosurgical treatments are planned in our department using intensity-modulated technique. Patients are immobilized using thermoplastic mask. A cone-beam computed tomography (CBCT) scan is acquired after the initial laser-based patient setup (CBCTsetup). The online adaptive replanning procedure we propose consists of a 6D registration-based mapping of the reference plan onto actual CBCTsetup, followed by a reoptimization of the beam fluences ("6D plan") to achieve similar dosage as originally was intended, while the patient is lying in the linac couch and the original beam arrangement is kept. The goodness of the online adaptive method proposed was retrospectively analyzed for 16 patients with 35 targets treated with CBCT-based frameless intensity modulated technique. Simulation of reference plan onto actual CBCTsetup, according to the 4 degrees of freedom, supported by linac couch was also generated for each case (4D plan). Target coverage (D99%) and conformity index values of 6D and 4D plans were compared with the corresponding values of the reference plans. Although the 4D-based approach does not always assure the target coverage (D99% between 72% and 103%), the proposed online adaptive method gave a perfect coverage in all cases analyzed as well as a similar conformity index value as was planned. Dose-guided radiosurgery approach is effective to assure the dose coverage and conformity of an intracranial target volume, avoiding resetting the patient inside the mask in a "trial and error" way so as to remove the pitch and roll errors when a robotic table is not available.

Structure and stability of a dimeric g-quadruplex formed by cyclic oligonucleotides.

We have studied the structure and stability of the cyclic dodecamer d, containing two copies of the human telomeric repeat. In the presence of sodium, NMR data are consistent with a dimeric structure of the molecule in which two cycles self-associate forming a quadruplex with three guanine tetrads connected by edgewise loops. The two macrocycles are arranged in a parallel way, and the dimeric structure exhibits a high melting temperature. These results indicate that cyclization of the phosphodiester chain does not prevent quadruplex formation, although it affects the global topology of the quadruplex.