Inter-fractional monitoring of [Formula: see text]C ions treatments: results from a clinical trial at the CNAO facility.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Reproductive biology and pollinators in two enantiostylous Qualea species (Vochysiaceae) in the Brazilian Cerrado.

Enantiostyly is a floral polymorphism in which two floral forms in the same species differ in deflection of the stigma to right or left position. In monomorphic enantiostylous plants, flowers of the two morphs occur within the same individual, usually in the same proportion. In self-compatible species the function of monomorphic enantiostyly is proposed to increase outcrossing rates and offer a reproductive advantage under pollination limitation. Enantiostylous species are usually self-compatible and show heteranthery, with poricide anthers and pollen as pollinator reward; however, there are families, such as Vochysiaceae, that have different characteristics. We analysed the reproductive system and pollination biology of Qualea parviflora and Q. multiflora, two enantiostylous species from the Brazilian Cerrado that have specific morphological and physiological traits. For this, we characterized flower traits, performed hand pollinations and studied floral visitors. We found no differences between morphs in the proportion of flowers, nectar produced or its concentration, pollen quantity and fruit set. Both species were self-incompatible and quite generalist regarding floral visitors. Enantiostyly in self-incompatible plants seems to confer a reproductive advantage by reducing self-interference resulting from stigma clogging. This novel result helps to expand our knowledge on this complex floral polymorphism and opens new avenues for future research on this topic.

Prevalence and characterization of breakthrough pain in cancer patients with proctalgia treated with 3D pelvic radiotherapy.

PURPOSE: Radiotherapy-induced dysfunction of the gastrointestinal tract is common in cancer patients and has a significant impact on their quality of life. In this study, we investigated the prevalence of breakthrough cancer pain (BTcP) in patients undergoing 3D pelvic radiotherapy and who had proctalgia. METHODS: This observational, multicenter, cross-sectional epidemiological study was performed in 13 Spanish hospitals. Data were obtained on the presence and characteristics of BTcP, demographics, common comorbidities, and treatments prescribed to the patients. RESULTS: The prevalence of BTcP in patients undergoing pelvic 3D external radiotherapy with proctalgia (N = 105) was 48.6% (95% CI 39.0-58.1%). BTcP was further characterized in 59 patients. The mean (± SD) intensity of the BTcP episodes was 7.45 ± 1.47 in a visual analog scale. We found several statistically significant associations between the descriptive variables of BTcP with demographic and clinical variables associated with the tumor or the patient, such as an increased number of BTcP episodes per day depending on the presence or absence of diabetes (p = 0.001, Chi-square) or time to the onset of pain relief depending on the location of the tumor (p = 0.019, Chi-square). Fentanyl was the drug of choice in BTcP episodes for 95% of the patients. CONCLUSIONS: This study demonstrated a high prevalence of BTcP prevalence in cancer patients undergoing pelvic 3D radiotherapy and with proctalgia. Although the variables determining the onset of BTcP are still unclear, our results could help in the design of future clinical studies addressing the treatment of BTcP in these patients.

Particle beam microstructure reconstruction and coincidence discrimination in PET monitoring for hadron therapy.

Positron emission tomography is one of the most mature techniques for monitoring the particles range in hadron therapy, aiming to reduce treatment uncertainties and therefore the extent of safety margins in the treatment plan. In-beam PET monitoring has been already performed using inter-spill and post-irradiation data, i.e. while the particle beam is off or paused. The full beam acquisition procedure is commonly discarded because the particle spills abruptly increase the random coincidence rates and therefore the image noise. This is because random coincidences cannot be separated by annihilation photons originating from radioactive decays and cannot be corrected with standard random coincidence techniques due to the time correlation of the beam-induced background with the ion beam microstructure. The aim of this paper is to provide a new method to recover in-spill data to improve the images obtained with full-beam PET acquisitions. This is done by estimating the temporal microstructure of the beam and thus selecting input PET events that are less likely to be random ones. The PET detector we used was the one developed within the INSIDE project and tested at the CNAO synchrotron-based facility. The data were taken on a PMMA phantom irradiated with 72 MeV proton pencil beams. The obtained results confirm the possibility of improving the acquired PET data without any external signal coming from the synchrotron or ad hoc detectors.

Monte Carlo simulation tool for online treatment monitoring in hadrontherapy with in-beam PET: A patient study.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60)

Introduction. Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer. Materials and methods. A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22). Results. here were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1). Discussion. Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt (AU)

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The impact of anthropogenic pressure on the virological quality of water from the Tiber River, Italy.

The objective of the present study was to assess the occurrence of major waterborne enteric viruses (enterovirus, norovirus, adenovirus, rotavirus, hepatitis A and E virus) along the Tiber River in Italy, in areas affected by different kinds of anthropogenic pressure (agricultural, urban, industrial and pristine). Moreover, in light of the recent abundant detection of human bocavirus in urban wastewater samples in Italy, the occurrence of this virus was also assessed. Virus detection was based on nested PCR followed by sequencing, and on real-time PCR. A correlation with anthropogenic pressure was observed. The urban and industrial areas were the most contaminated (100 and 75% of samples were positive for at least one virus respectively). The agricultural area was less contaminated, with 50% of samples positive. None of the samples collected in a pristine area were positive for viruses. The most frequently detected virus was human bocavirus, identified in 37·5% of samples, followed by norovirus and enterovirus (28% each) and adenovirus (21·6%). Rotavirus, and hepatitis A and E viruses were less common (<9%). Although Human Bocavirus is not considered a waterborne pathogen, the widespread contamination of river waters suggests that virus transmission via the water route should not be neglected. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge, this study constitutes the first attempt to assess the occurrence of enteric viruses in river waters, in areas differentially influenced by anthropogenic pressure. Enteric viruses (enterovirus, norovirus, adenovirus, rotavirus, hepatitis A and E viruses, and bocavirus) were widespread in the industrial and urban areas, and were less frequently detected in the agricultural area. Interestingly, human bocavirus was the most frequently detected virus, outnumbering even adenoviruses, known to be widespread in water environments. The widespread presence of bocavirus in surface waters suggests that a potential role of water in its transmission should not be excluded.

Gynecological brachytherapy for postoperative endometrial cancer: dosimetric analysis (Ir-192 vs Co-60).

INTRODUCTION: Endovaginal brachytherapy treatment dosimetry differences were studied using Ir-192 or Co-60 sources for postoperative endometrial cancer. MATERIALS AND METHODS: A prospective descriptive study was conducted. Thirty-six dosimetry plans of different patients were studied (15 by Ir-192 and 21 by Co-60). Variables studied included D2cc Rectum, D2cc Bladder, D2cc Sigmoid, dose percentage at point 0 (applicator surface on the top of the cylinder) and dose percentage at point 1 (5 mm deep on the top of the cylinder). A comparative analysis was performed of the values obtained from each variable between Ir-192 and Co-60 treatments. We compared average of each variables between Iridium and Cobalt by T Student for independent samples (SPSS 22). RESULTS: There were no significant differences on using Ir-192 or Co-60 by variables, except for dose percentage at point 1 in which we detected significant differences (Table 1). Table 1 The results Variables Sources Iridium 192 Cobalt 60 D2cc Rectum (mean dose) [rank] 6.01 Gy [3.99-7.90] 5.28 Gy [3.87-6,34] D2cc Bladder (mean dose) [rank] 5.82 Gy [4.20-8.38] 5.05 Gy [2.23-6.95] D2cc Sigmoid (mean dose) [rank] 4.43 Gy [1.66-6.67] 2.33 Gy [0.60-4.28] Dose percentage at point 0a (mean) [rank] 210.74% [120.90-234.90] 204.75% [177.10-223] Dose percentage at point 1b (mean) [rank] 93.49% [87.30-100.60] 100.11% [96.70-102] aPoint 0: point to the applicator surface bPoint 1: point to 5 mm applicator surface DISCUSSION: Brachytherapy treatment dosimetry plans are similar using Ir-192 or Co-60, except dose percentage at point 1. In the scientific literature, some differences exist and there are some advantages in using cobalt.

Full-beam performances of a PET detector with synchrotron therapeutic proton beams.

Treatment quality assessment is a crucial feature for both present and next-generation ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET signals by [Formula: see text]-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in sub-millimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data.

Endonasal mucosal contact points in chronic migraine.

Some anatomo-functional alterations of the nose may be considered as possible causes of headache: deviations of the nasal septum, abnormal turbinates, especially middle or superior, with consequent areas of mucosal contact with the septum. This study was performed on 100 subjects, 27 chronic migraine (CM) sufferers and 73 subjects who never suffered from migraine as control group. In the CM group, a direct endoscopic assessment was carried out in order to search for mucosal points of contact. Following the endoscopy, the patients underwent a computerized tomography (CT) in order to confirm the mucosal contact and for a better evaluation of its localization. The control group (C group) consisted of subjects who underwent a CT of the skull for various reasons. In CM group, a mucosal contact was highlighted in 14 patients (51.8 %); it was unilateral in 50 % of cases. In C group, the contact was present in 27 cases (36.9 %); in 81.5 % of them (n = 22), it was unilateral. A single site of contact was present in 6 (22 %) patients in CM group and 20 (27.3 %) patients in C group; more sites, in 8 (29.6 %) CM group patients and in 7 (9.5 %) patients of the C group. The connection between subjects and the number of single or multiple contacts in the two groups was statistically significant (p = 0.049). Furthermore, the frequency of the septum-middle turbinate was significantly (p = 0.0013) more frequent in CM sufferers (13/14) compared with control subjects (11/27). This study suggests, although with extremely early data, the need to select carefully patients for a possible surgical approach, using various parameters: in particular, the site of the mucosal contact, favoring the cases with multiple areas of contact, mainly between septum-middle turbinate and septum-superior turbinate.

Compatibility between coherent reflective burst-mode PON and TWDM-PON physical layers.

We discuss the compatibility between reflective PON architectures and the recently defined ITU-T G.989.1 TWDM-PON. Focusing on the upstream, we experimentally demonstrate that, by using burst-mode coherent detection at OLT, reflective PON can achieve the specification target set for TWDM-PON, without requiring precise wavelength accuracy at ONU. Compared to the companion ECOC 2013 paper, we investigate on the differential optical path loss (DOPL) issue, proposing a simple SOA gain control algorithm to achieve reliable transmission for DOPL up to 17 dB.

Sexual reproduction of the pentaploid, short-styled Oxalis pes-caprae allows the production of viable offspring.

Reproduction is a key factor for the successful establishment and spread of introduced species. Oxalis pes-caprae is a tristylous species with a self- and morph-incompatibility sexual system that, in the invaded range of the western Mediterranean Basin, has been found to reproduce asexually because only the pentaploid, short-styled morph (5x S-morph) was introduced. The objective of this study was to test the ability of the 5x S-morph of O. pes-caprae to produce viable offspring in the absence of compatible mates, exploring the hypothesis that new morphs could have emerged by sexual reproduction events of the initially introduced morph. Pollen germination, pollen tube development, fruit and seed production, seed germination and offspring ploidy levels were analysed after controlled hand-pollinations to assess self- and morph-incompatibility and production of viable gametes by the 5x S-morph. The self-incompatibility system is still operating, but a partial breakdown in the morph-incompatibility system combined with the production of viable gametes was observed, allowing sexual reproduction of the 5x S-morph in the invaded range. The ability of the 5x S-morph to reproduce sexually may have major consequences for the dynamics of invasive populations of O. pes-caprae and could be one of the factors involved in the occurrence of new floral morphs in this invaded range.

Quantifying reciprocity in distylous and tristylous plant populations.

Reciprocal herkogamy (heterostyly) is an example of extreme relevance of accuracy of the location of the sexual organs within some floral systems. It involves the reciprocal positioning of anthers and stigmas in flowers of different plants within the same population, and the accuracy of this positioning is important to promote out-cross pollination, prevent self-interference, or both. Hence, several indices have been proposed to quantify reciprocity, most of them for populations with two different morphs (distylous). Here, we propose an extension of our index of reciprocity for distylous populations to be applied also to populations with three morphs (tristylous), allowing effective comparisons of reciprocity between tristylous, but also distylous populations. As for the distylous version, the index is based on comparison of the position of every single sexual organ in the sample with each and every organ of the opposite sex, for each of the three possible organ levels. Due to the massive amount of calculations required, a macro was developed that is available as Supplementary Information and at the website of the authors. The index and macro were tested on several hypothetical tristylous and distylous populations with predetermined mean and dispersion of sexual organs at each level, as well as on several actual tristylous and distylous populations. The index proposed is a solid tool for the study of reciprocity in distylous and tristylous populations. Comparisons between distylous and tristylous populations are easily performed and can be readily interpreted. The applicability of the index is facilitated through the software provided.

Characterization of uncooled RSOA for upstream transmission in WDM reflective PONs.

We investigate on the uncooled RSOA driving parameters in WDM reflective PONs, focusing on an upstream path at 1.25 Gbit/s using pure binary modulation. We show how the optimal values change using direct-detection or self-coherent receivers. In particular, for the latter, the driving point optimization allows a gain of more than 3 dB in terms of ODN loss compared to a standard On-Off Keying, generating a quasi-PSK modulation. We also address operating temperature and wavelength dependence issues.

Unusual heterostyly: style dimorphism and self-incompatibility are not tightly associated in Lithodora and Glandora (Boraginaceae).

BACKGROUND AND AIMS: Heterostyly is a floral polymorphism characterized by the reciprocal position of stamens and stigmas in different flower morphs in a population. This reciprocal herkogamy is usually associated with an incompatibility system that prevents selfing and intra-morph fertilization, termed a heteromorphic incompatibility system. In different evolutionary models explaining heterostyly, it has been alternately argued that heteromorphic incompatibility either preceded or followed the evolution of reciprocal herkogamy. In some models, reciprocal herkogamy and incompatibility have been hypothesized to be linked together during the evolution of the heterostylous system. METHODS: We examine the incompatibility systems in species with different stylar polymorphisms from the genera Lithodora and Glandora (Boraginaceae). We then test whether evolution towards reciprocal herkogamy is associated with the acquisition of incompatibility. To this end, a phylogeny of these genera and related species is reconstructed and the morphological and reproductive changes that occurred during the course of evolution are assessed. KEY RESULTS: Both self-compatibility and self-incompatibility are found within the studied genera, along with different degrees of intra-morph compatibility. We report for the first time extensive variability among members of the genus Glandora and related species in terms of the presence or absence of intraspecies polymorphism and heteromorphic incompatibility. Overall, our results do not support a tight link between floral polymorphism and incompatibility systems. CONCLUSIONS: The independent evolution of stylar polymorphism and incompatibility appears to have occurred in this group of plants. This refutes the canonical view that there is strong linkage between these reproductive traits.

Optimization of self-coherent reflective PON to achieve a new record 42 dB ODN power budget after 100 km at 1.25 Gbps.

We demonstrate a greater than 42 dB optical distribution network power budget in the upstream of a 1.25 Gbps self-coherent reflective PON after 100 km of installed fibers, using off-the-shelf optoelectronic components, improving our previous result by 4 dB. We discuss all system optimizations introduced in the setup in order to reach such a result, including 8B/10B high-pass filtering and Faraday rotation at the ONU.

P450-based porous silicon biosensor for arachidonic acid detection.

A porous silicon biosensor based on P450 enzyme for arachidonic acid detection was developed. A new transduction method is presented with a simultaneous measurement of refractive index and fluorescence intensity changes when the analyte is binding to an enzyme on the porous silicon surface. A fluorophore bound to a cysteine residue in an allosteric position of the haem domain (BMP) of cytochrome P450 BM3 enhances its fluorescence intensity upon interaction with its substrate arachidonic acid, involved in diseases such as Alzheimer's, liver cancer and cellular inflammation processes. BMP has been anchored on porous silicon surface and the new transduction method has been successfully exploited to develop a biosensor for arachidonic acid, reaching a detection limit of 10 µM arachidonic acid in a dynamic range of 10-200 µM. Moreover, the change of the refractive index has been also monitored at the same time, displaying a higher detection limit of 30 µM. Preliminary test were also conducted in plasma proving the high specificity and selectivity of the sensor even in presence of interferents in the range of 50-100 µM. Here we suggest these two detection systems could be used simultaneously to increase the accuracy and the dynamic range of the sensor avoiding a false positive response.

Reciprocal style polymorphisms are not easily categorised: the case of heterostyly in Lithodora and Glandora (Boraginaceae).

Interest in reciprocal floral polymorphisms, such as heterostyly, has increased in recent decades because they can be used as suitable model systems to study mechanisms of outbreeding and disassortative mating in plants. Heterostylous plants are characterised by the presence of discrete morphs that differ in sex organ position and in some other ancillary traits. As regards sex organ deployment, different types of polymorphisms have been described, depending on number and type of discrete classes present in populations and degree of reciprocity between them. However, a clear-cut characterisation of stylar polymorphisms does not appear to be the best approach when there is great variability among populations because of continuous variation of some of traits examined. A recent study in Lithodora sensu lato (recently split into two separate genera, Lithodora and Glandora) showed a wide variation in sex organ position across species in the genus, which warrants precise population analysis of stylar polymorphism and its reciprocity. We provide a detailed morphometric analysis of flower sexual traits and include those considered to be ancillary characters. We report a wide variation in these traits in populations of Lithodora s.l. and highlight the subjectivity of the former characterisation of style polymorphism based on visual inspection. Ancillary traits appear repeatedly in Lithodora and Glandora, particularly in the latter. The appearance of these traits seems to be related to greater reciprocity between sexual whorls in Glandora, with the exception of G. prostrata. These results agree with evolutionary steps proposed in the build-up of heterostyly according to some evolutionary models. We also examined variation in polymorphisms in light of current models for evolution of heterostyly, and, more specifically, we sought to verify the prediction that flower traits as a whole (i.e., flower integration) respond to selective pressure to assure the exact location of pollen on the pollinator body. Most reciprocal populations and species, where between-morph pollen transfer is expected to be higher, would show greater integration. Our results confirm this hypothesis.

Patterns of style polymorphism in five species of the South African genus Nivenia (Iridaceae).

BACKGROUND AND AIMS: Heterostylous plants have been characterized by the presence of two or three discrete morphs that differ in their sex organ position within populations. This polymorphism is widely distributed among the angiosperms, but detailed studies are limited to few taxonomic groups. Although a small representation, evolutionary meaningful variations of the heterostylous syndrome have been reported when precise measurements of the sexual whorls were taken. A thorough exploration of groups where heterostyly has been reported should offer new opportunities to further testing the evolutionary hypotheses explaining heterostyly. Here, the traits defining heterostyly were explored in half of the species in Nivenia, the only genus of Iridiaceae where heterostyly has been reported. METHODS: Detailed morphometric analysis of the flower sexual whorls and some traits considered as ancillary are supplied to determine for each population (a) the kind of stylar polymorphism, (b) the morph ratio and (c) the degree of reciprocity between sexual whorls. Also the rates of assortative (within morph) versus disassortative (between morphs) pollen transfer were estimated by analysing pollen loads on stigmas. The association between floral phenotypic integration and the reciprocity between sexual whorls was estimated; both characteristics have been quoted as dependent on the accuracy of the fit between pollinators and flowers and therefore related to the efficiency of pollen transfer. KEY RESULTS: Different types of polymorphism, differing in their degree of reciprocity, were found in Nivenia. Effective disassortative mating appears to be common, since (a) all dimorphic populations show equal morph-ratios (isoplethy), and (b) the pollen placed on the stigmas of each morph is likely to be coming from the other (complementary) morph. The most reciprocal populations of the heterostylous species have also the highest values of phenotypical integration. CONCLUSIONS: Stigma height dimorphism, as opposed to distyly, is proven for the first time in Nivenia. The presence of different types of polymorphism within the genus is consistent with hypotheses of the evolution of heterostyly. The role of the pollinators as the leading force of the transition seems to be apparent, since floral integration is related to reciprocity.