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Background Clinical and preclinical studies have revealed that alterations in DNA damage response (DDR) pathways may play an important role in prostate cancer (PCa) etiology and progression. These alterations can influence PCa responses to radiotherapy and anti-androgen treatment. The identification of DNA repair gene aberrations in PCa has driven the interest for further evaluation whether these genetic changes may serve as biomarkers for patient stratification. Methods In this review, we summarize the current knowledge on DDR alterations in PCa, their potential impact on clinical interventions and prospects for improved management of PCa. We particularly focus on the influence of DDR gene mutations on PCa initiation and progression and describe the underlying mechanisms. Results and Conclusions A better understanding of these mechanisms, will contribute to better disease management as treatment strategies can be chosen based on the specific disease properties, since a growing number of treatments are targeting DDR pathway alterations (such as Poly(ADP-ribose) polymerase inhibitors). Furthermore, the recently discovered crosstalk between the DDR and androgen receptor signaling opens a new array of possible strategies to optimize treatment combinations. We discuss how these recent and ongoing studies will help to improve diagnostic, prognostic and therapeutic approaches for PCa management.

PUROSE Ethiopia has one cobalt radiotherapy (RT) machine to serve a population of more than 100 million. The purpose of this study was to report on patterns of palliative RT of bone metastasis in a severely low-capacity setting. PATIENTS AND METHODS Patient and treatment characteristics of patients irradiated for palliation of symptomatic bone metastasis were extracted from a retrospective database of patients treated between May 2015 and January 2018. This database included a random sample of 1,823 of the estimated 4,000 patients who were treated with RT within in the study period. Associations between the applied RT schedule and patient and tumor characteristics were evaluated with the χ2 test. Hypothetical savings of RT sessions and time were compared in the case of a single-fraction policy. RESULTS From the database, 234 patients (13%) were treated for bone metastasis. Most patients were ≤ 65 years of age (n = 189; 80%) and female (n = 125; 53%). The most common primary sites were breast (n = 82; 35%) and prostate (n = 36; 15%). Fractionated regimens were preferred over single fraction: 20 Gy in 5 fractions (n = 192; 82.1%), 30 Gy in 10 fractions (n = 7; 3%), and 8 Gy in 1 fraction (n = 28; 12%). Factors associated with single-fraction RT included nonaxial sites of bone metastasis ( P < .01) and an address outside Addis Ababa ( P ≤ .01). If single-fraction RT would have been given uniformly for bone metastasis, this would have resulted in a 78% reduction in the number of RT sessions and 76% reduction in total RT time. CONCLUSION The pattern of palliative RT for bone metastasis in Ethiopia favors fractionated regimens over single fraction. Efforts should be made to adopt evidence-based and cost-effective guidelines.

Sorrel (Rumex acetosa L.) is a perennial wild herb appreciated as a folk medicine and for use in folk-traditional cuisines, and its nutraceutical properties are increasingly known and studied. Nowadays, there is a lack of knowledge about the possibility of using this species as fresh-cut produce, and no reports have investigated the physiological/biochemical changes of sorrel leaves upon storage. To test the aforementioned, sorrel seedlings were cultivated in a floating system and two consecutive harvests took place: the first cut at 15 days (C1) and second cut at 30 days (C2) after sowing. Fresh-cut sorrel leaves from C1 and C2 were stored in plastic boxes at 4 &deg, C for 15 days and chlorophylls, carotenoids, total phenols, flavonoids, ascorbic acid, and antioxidant capacity were evaluated during the storage period. During storage, sorrel leaves from the same cut did not show significant changes in total phenolic content and antioxidant capacity, which represents a positive outcome for the maintenance of the nutraceutical value of this species. For this reason, sorrel may be a very promising species as a &ldquo, new&rdquo, fresh-cut leafy vegetable. However, some differences were observed between the two cuts, especially in the total flavonoid and the total ascorbic acid contents. While promising, further research will be necessary to standardize the yield and the nutraceutical content of this species in different cuts, which will be necessary to introduce and promote sorrel to consumers.

Diverse vegetable production systems are an essential part of European food production. Nitrogen (N) fertiliser and commonly irrigation are integral to European vegetable cropping. Applications of N and irrigation are generally based on the experience of growers and technical advisors. Commonly, applications of both exceed crop requirements causing nitrate (NO3−) leaching. This can result in NO3− contamination of underlying aquifers, which can also contribute to eutrophication of natural surface water bodies. Various agronomic characteristics of vegetable crops such as shallow roots, low density planting and multiple cropping exacerbate the risk of NO3− leaching. Because of health and environmental concerns related to NO3− contaminated groundwater and eutrophication, there is appreciable and increasing societal pressure to reduce these environmental impacts. Additionally, there is increasing societal pressure to reduce emissions of phosphorus and plant protection products to water bodies. The European Union (EU) has passed several Directives to reduce contamination of water bodies from agriculture. Member States of the EU are required to comply and implement these legislations. European consumers are increasingly concerned that their food is produced with minimal environmental impact. Product certification schemes, with requirements or recommendation for N and irrigation management, are required in order to sell vegetables through many European supermarket chains. Because of legislative and consumer pressure, European vegetable growers will increasingly need to adopt science-based management approaches to reduce contamination of water bodies from their farming operations. The virtual Special Issue “Reducing contamination of water bodies from European vegetable production systems” consists of eight review papers that revise the options available to European vegetable growers. The issues facing particular European vegetable production systems are also addressed.

The paper presents an Internet-of-Things based agricultural decision support system for crop growth. A dynamic Bayesian network (DBN) relates indicative parameters of crop development to environmental control parameters via unobserved (hidden) Markov states. The expectation-maximization algorithm is used to track the states and to learn the parameters of the DBN. The steady state information is then used to derive a predictor for the measurement data a few days ahead. The proposed DBN avoids time-consuming training cultivation cycles, as only data of the current cultivation cycle are available to the algorithm. Three cultivation cycles of lettuce have been used to test the performance of the proposed DBN. The environmental parameters were temperature, solar irradiance and vapor-pressure deficit. The measurement data include evapotranspiration at granularity equal one day, and leaf-area index and dry weight, at granularity equal one week. It turned out that accurate measurement data prediction a few days ahead is possible even if the number of data samples is low.

Seedlings of Rumex acetosa L. (sorrel) were grown in floating system and two consecutive cuts took place: 15 (C1) and 30 (C2) days after sowing. An untargeted metabolomics approach was utilised to fingerprint phenolics and other health-related compounds in sorrel leaves, as well as to unveil differences between the two cuts. The untargeted approach allowed to putatively identify 458 metabolites considering both the cuts. Three new terpenoids and two new phenylpropanoid glycosides (dihydrosyringin and dihydroconiferin) with antifungal and anti-inflammatory activity were annotated. Overall, leaves from C2 had lower level of secondary metabolites (44 were down-accumulated), especially sesquiterpenes and stilbenes. Conversely, anthocyanins showed a relevant increase in C2 than in C1 leaves. The dataset suggests that sorrel leaves represent a good source of nutraceutical compounds and unveils the pivotal effect of pre-harvest factor in secondary metabolite profile.

277 Background: The prognostic importance of local failure (LF) after definitive radiotherapy (RT) in patients with NCCN intermediate- (IRPCa) and high-risk prostate cancer (HRPCa) remains unclear, particularly given the likelihood that occult distant metastases (DMs) at presentation may be the true driver of natural history. Here, we leverage individual patient data (IPD) from 18 randomized control trials (RCTs) to evaluate the prognostic impact of LF and the kinetics of DM after RT. Methods: IPD for 18 RCTs were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium, comprising a total of 12533 patients (6288 HRPCa & 6245 IRPCa). Multivariable Cox proportional hazards (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), DM-free survival (DMFS) & LF as a time-dependent covariate, adjusted for clinicodemographic parameters. Markov PH models, defined via transitions between 4 states, were developed to evaluate the aforementioned relationship. Proportional hazards assumption was imposed and examined for both models. Time is from randomization. Results: Median follow-up was 9.1 years. There were 795 (13%) LF & 1288 (21%) DM events for patients with HRPCa; these numbers were 449 (7%) & 451 (7%) for IRPCa. For HRPCa & IRPCa, 81% and 81% of DMs developed from a clinically relapse-free state (cRFS), with a median time of 46 and 60 months, respectively (p < 0.0001). 39% & 13% of DM events occurred within 2 years after RT for HRPCa & IRPCa, respectively. At later time points, DM events were more likely to emerge after an LF event for both HRPCa (9% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.001) and IRPCa (10% vs. 34% between 0-2 vs. 8-10 years post-RT, p = 0.008). LF was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06–1.30), PCSS (HR 2.02, 95% CI 1.75-2.33) & DMFS (HR 1.94, 95% CI 1.75–2.15) (p < 0.01 for all) in patients with HRPCa. LF was also significantly associated with DMFS (HR 1.57, 95% CI 1.36–1.81) but not OS in patients with IRPCa. Patients who had not transitioned to the LF state had a significantly lower HR of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.32, 95% CI 0.21–0.50, p < 0.001). Conclusions: LF is an independent prognosticator of OS, PCSS & DMFS in HRPCa and of DMFS in IRPCa. The predominant mode of DM development is from the cRFS state, underscoring the importance of accurate upfront staging & systemic therapy. However, particularly at late time points, an increasing proportion of DM events originated after diagnosis of a LF, constituting a “second wave” of DM events. This suggests that optimizing local control is also important, though the majority of DM events appear prior to a clinically-detected LF.

Flaxseed could be suitable for obtaining high-quality sprouts and microgreens thanks to high amounts of nutrients and antioxidant, antidiabetic, and anticancer compound content in its seeds. Recent studies highlighted that seedling growth, nutritional compound, and secondary metabolite content can be strongly managed by regulation of the light spectrum used during germination. The present study intended to shed light on flaxseed as emerging and novel species for sprouts and microgreens and to evaluate the effect of light, with different spectrum compositions (100% blue, 100% red, 100% green, and red:green:blue—1:1:1) on the performance of flax microgreens and sprouts grown indoors under controlled conditions. Microgreens showed, compared to sprouts, a higher chlorophyll (+62.6%), carotenoid (+24.4%), and phenol content (+37.8%), antioxidant capacity (+25.1%) and a lower dry matter content (−30.7%). Besides, microgreens treated with 100% blue light were characterized by the highest content of flavonoids (2.48 mg CAE g−1 FW), total phenols (3.76 mg GAE g−1 FW), chlorogenic acid (1.10 mg g−1 FW), and antioxidant capacity (8.06 µmol TEAC g−1 FW). The paper demonstrates the feasibility of obtaining flax sprouts and microgreens indoors with a considerable antioxidant capacity and health-promoting compounds by modulating the light spectrum.

PURPOSE Radiotherapy (RT) is an essential component of cancer treatment. There is a lack of RT services in sub-Saharan Africa as well as limited knowledge regarding clinical practices. The purpose of this study was to identify and describe the patterns for RT treatment in Ethiopia. METHODS AND MATERIALS We performed a retrospective analysis of 1,823 patients treated with cobalt RT at a large referral hospital in Addis Ababa, Ethiopia, from May 2015 through January 2018. Paper charts were reviewed for patient and treatment characteristics. Descriptive statistics were computed using SPSS (IBM, Armonk, NY). RESULTS Among patients treated for cancer, 98% (n = 1,784) were adults, 78% (n = 1,426) were female, 5% (n = 85) were HIV positive, 30% (n = 555) were from Addis Ababa, and the median age was 48 years (interquartile range [IQR], 38-58 years). Cervical cancer was the most frequent cancer treated (47%, n = 851), followed by breast cancer (15%, n = 274) and head and neck cancer (10%, n = 184). Seventy-three percent of patients (n = 1,339) presented at a late stage, and 62% (n = 1,138) received palliative RT. The wait times were the shortest for patients receiving palliative treatment (median, 0 days; IQR, 0-15 days; n = 1,138), whereas wait times were longer for patients receiving curative treatment (median, 150 days; IQR, 60-210 days; n = 685). Three percent of patients (n = 56) had documented grade 3 or 4 acute toxicity; of these, 59% (n = 33) were patients with head and neck cancer. CONCLUSION Cervical cancer accounted for half of patients treated; thus, a majority of patients were adult females. Most patients had advanced-stage cancer, and goals of care were palliative. Wait times were long for patients with curative-intent cancer as a result of low capacity for RT services.

Sexual concerns are common after haematopoietic cell transplantation (HCT). Exposure to total body irradiation (TBI), alkylating agent and graft versus host disease (GvHD) can all affect sexual function, leading to problems in sexual desire, arousal and the orgasm phase of the sexual response cycle. In high-risk haematological malignancies, such as acute leukaemia and myelodysplastic syndromes, HCT often offers the highest chance for long-term survival. In addition, these haematological diseases and HCT can have an impact on body image, self-esteem, (sexual) relationship and psychosocial factors, all of which are able to affect sexuality and sexual function. Five years post HCT, 80% of the female survivors and 46% of the male survivors report sexual dysfunction. It has been shown that these patients cope better after having discussed sexual health. While healthcare providers (HCPs) have the responsibility to address sexual issues, it has been demonstrated that 48%–82% HCT recipients reported not having discussed sexual issues with their HCPs and that only one-third of the HCPs routinely discussed sexual issues with their patients. HCPs describe a lack of knowledge and being uncomfortable with the topic as the most important reasons for not addressing sexual functioning. Even so, it would help >90% HCPs if the patient initiated discussing sexual issues. However, to empower patients addressing sexual issues, adequate comprehensive patient information is needed. In an effort to better meet the patients' need, a patient information sheet: ‘Information for patients undergoing Hematopoietic Cell Transplantation: the impact of the disease and treatment on sexual function and sexuality', has been created. In this review, we describe what is known about the impact of HCT on sexual function and briefly the management of sexual problems.

Iodine deficiency is a serious world-wide public health problem, as it is responsible for mental retardation and other diseases. The use of iodine-biofortified vegetables represents a strategic alternative to iodine enriched salt for people with a low sodium diet. However, at high concentrations iodine can be toxic to plants. Therefore, research on plant iodine toxicity is fundamental for the development of appropriate biofortification protocols. In this work, we compared two cultivars of sweet basil (Ocimum basilicum L.) with different iodine tolerance: “Tigullio,” less tolerant, with green leaves, and “Red Rubin,” more tolerant and with purple leaves. Four greenhouse hydroponic experiments were conducted in spring and in summer with different concentrations of iodine in the nutrient solution (0.1, 10, 50, 100, and 200 μM), supplied as potassium iodide (KI) or potassium iodate (KIO3). Plant growth was not affected either by 10 μM KI or by 100 μM KIO3, while KI concentrations higher than 50 μM significantly reduced leaf area, total plant dry matter and plant height. The severity of symptoms increased with time depending on the cultivar and the form of iodine applied. Growth inhibition by toxic iodine concentrations was more severe in “Tigullio” than in “Red Rubin,” and KI was much more phytotoxic than KIO3. Leaf iodine concentration increased with the iodine concentration in the nutrient solution in both varieties, while the total antioxidant power was generally higher in the purple variety. In both basil cultivars, a strong negative correlation was found between the photosynthesis and the leaf iodine content, with significant differences between the regression lines for “Tigullio” and “Red Rubin.” In conclusion, the greater tolerance to iodine of the “Red Rubin” variety was associated with the ability to withstand higher concentrations of iodine in leaf tissues, rather than to a reduced accumulation of this element in the leaves. The high phenolic content of “Red Rubin” could contribute to the iodine tolerance of this purple cultivar.

Spinach is one of the most important green-leafy vegetables, consumed worldwide, and its intake is beneficial for human beings. In this crop, produce yield and quality are closely related to plant nitrogen (N) nutrition. A precise supply of N is also essential for high environmental and economic sustainability. Main aims of the work were: i) to establish relationships between produce yield or quality and mineral N availability in the root zone; and ii) to define an optimal mineral N level to be maintained in the root zone for spinach. Eight experiments were carried out during a four-year-long period under typical Mediterranean climate conditions. Different amounts of N fertilisers were supplied leading to twenty different levels of mineral N in the root zone. Experimental measurements included climate parameters, plant growth, tissue and soil analyses, produce yield and quality indicators. A segmented linear model significantly represented the relationship between crop yield (1.7 to 21.7 t ha–1) and soil mineral N concentration (7.6 to 41.0 mg kg–1). Basing on this model, an optimal mineral N threshold was fixed at 23.4 mg kg–1. Above this threshold, crop yield did not show any significant variations as well as tissue characteristics and produce quality. Plants grown under suboptimal N levels showed reduction in growth, tissue mineral (nutrients) content, and SPAD index. The proposed models could be implemented in fertilisation protocols for the optimization of N supply and the estimation of spinach growth and yield.

The majority of adult patients have sexual concerns after post-haematopoietic cell transplantation. Even so, health-care professionals (HCP) do not routinely discuss these problems. We, therefore, surveyed all the members of the European Society for Blood and Marrow Transplantation to evaluate the barriers and facilitators to discussing sexual issues. The 73-item web-survey was completed by 166 registered nurses (RNs) and 126 medical doctors (MDs). Sixty-eight percent reported that they seldom discussed sexual issues. Younger MDs (p < 0.001) and those who work in non-western European countries (p = 0.003), RNs with probably less sexual education themselves (p = 0.002), MDs and RNs who have limited knowledge about sexual complications (p < 0.001) and MDs and RNs who feel uncomfortable discussing sexual issues (p < 0.001) are all less likely to discuss these matters. The major perceived barriers were that patients might be embarrassed if sexual issues were discussed in the presence of a relative (60% RNs, 67% MDs) and that professionals prefer patients to raise sexual issues themselves (54% RNs, 44% MDs). The most important perceived facilitator was for the patient to initiate discussion (≥ 90% for RNs and MDs). Overall, haematopoietic cell transplantation survivors may not be receiving the support on sexual issues they probably need.

Background and purpose: To explore the use of texture analysis (TA) features of patients' 3D dose distributions to improve prediction modelling of treatment complication rates in prostate cancer radiotherapy. Material and methods: Late toxicity scores, dose distributions, and non-treatment related (NTR) predictors for late toxicity, such as age and baseline symptoms, of 351 patients of the hypofractionation arm of the HYPRO randomized trial were used in this study. Apart from DVH parameters, also TA features of rectum and bladder 3D dose distributions were used for predictive modelling of gastrointestinal (GI) and genitourinary (GU) toxicities. Logistic Normal Tissue Complication Probability (NTCP) models were derived, using only NTR parameters, NTR + DVH, NTR + TA, and NTR + DVH + TA. Results: For rectal bleeding, the area under the curve (AUC) for using only NTR parameters was 0.58, which increased to 0.68, and 0.73, when adding DVH or TA parameters respectively. For faecal incontinence, the AUC went up from 0.63 (NTR only), to 0.68 (+ DVH) and 0.73 (+ TA). For nocturia, adding TA features resulted in an AUC increase from 0.64 to 0.66, while no improvement was seen when including DVH parameters in the modelling. For urinary incontinence, the AUC improved from 0.68 to 0.71 (+ DVH) and 0.73 (+ TA). For GI, model improvements resulting from adding TA parameters to NTR instead of DVH were statistically significant (p

Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI. Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed. Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome. Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

Purpose/objective: Assess to what extent the use of automated treatment planning would have reduced organ-at-risk dose delivery observed in the randomized HYPRO trial for prostate cancer, and estimate related toxicity reductions. Investigate to what extent improved plan quality for hypofractionation scheme as achieved with automated planning can potentially reduce observed enhanced toxicity for the investigated hypofractionation scheme to levels observed for conventional fractionation scheme. Material/methods: For 725 trial patients, VMAT plans were generated with an algorithm for automated multi-criterial plan generation (autoVMAT). All clinically delivered plans (CLINICAL), generated with commonly applied interactive trial-and-error planning were also available for the investigations. Analyses were based on dose-volume histograms (DVH) and predicted normal tissue complication probabilities (NTCP) for late gastrointestinal (GI) toxicity. Results: Compared to CLINICAL, autoVMAT plans had similar or higher PTV coverage, while large and statistically significant OAR sparing was achieved. Mean doses in the rectum, anus and bladder were reduced by 7.8 +/- 4.7 Gy, 7.9 +/- 6.0 Gy and 4.2 +/- 2.9 Gy, respectively (p = 2 GI toxicity, rectal bleeding and stool incontinence were reduced from 23.3 +/- 9.1% to 19.7 +/- 8.9%, from 9.7 +/- 2.8% to 8.2 +/- 2.8%, and from 16.8 +/- 8.5% to 13.1 +/- 7.2%, respectively (p

Wild edible plant species are often more tolerant to salinity than many crop plants. Considering the salinization of irrigation water that is progressively affecting the Mediterranean region and the market demand for new plant foods, the cultivation of wild edible species could represent a valid alternative to conventional vegetable crops. In this study, Reichardia picroides (L.) Roth, a widespread spontaneous herb of ethnobotanical tradition, was grown for four or six weeks under a greenhouse in a floating system for the production of baby leaves. In order to improve the nutraceutical quality of the tissues, the plants were exposed to the following NaCl concentrations in the nutrient solution: 1.7 (control), 25, 50, and 100 mM. The results showed that a 4-week growing period in a floating system with 50 mM NaCl in the nutrient solution increased the content of bioactive molecules without affecting the fresh yield. After six weeks of cultivation, despite a decrease in biomass production as compared with the control, the leaves of salt-treated plants contained higher levels of bioactive molecules along with lower amounts of nitrate ion.

Background Choice of prostate cancer treatment is frequently influenced by the expected chance of treatment-induced side effects such as erectile dysfunction (ED). However, great discrepancy in cited ED rates exists in the contemporary radiation therapy literature. Aim To analyze the reported ED rates and cause of discrepancies and explore the strengths and limitations in the literature on radiation-induced ED. Methods We performed a PubMed literature search and reviewed the literature on ED rates associated with external-beam radiotherapy and brachytherapy from the past 10 years. Eighteen studies were eligible for inclusion and subsequently reviewed. Outcomes Variables required for interpretation of erectile function outcomes, including patient demographics, treatment characteristics, and sexual function outcomes. Results A large variety in the reported incidence of ED was found among studies. In part, these differences resulted from large variations in (i) study populations, (ii) patient characteristics, (iii) treatment characteristics, (iv) prescription of androgen deprivation therapy, (v) means of data acquisition, (vi) definitions of ED, (vii) temporal considerations, and (viii) erectile aid use. Relevant data required for adequate appraisal of sexual function outcomes were not always reported. Clinical Implications Based on the present findings, we present general recommendations for reporting of erectile function outcomes after radiotherapy for prostate cancer. These should improve future reports. Strengths and Limitations This is the first report that presents general requirements on reporting erectile function outcomes in the setting of radiotherapy for prostate cancer. We did not conduct a formal meta-analysis because we focused on concepts of research design; this might be considered a limitation. Conclusion In this review, we have highlighted the strengths and deficiencies of the current literature on ED after external-beam radiotherapy and brachytherapy for prostate cancer. We have made general recommendations to achieve some degree of standardization among reports and improve clinical interpretability.

Relative increase of grade 4 and presence of invasive cribriform and/or intraductal carcinoma have individually been associated with adverse outcome of Gleason score 7 (GS 7) prostate cancer. The objective of this study was to investigate the relation of Gleason grade 4 tumor percentage (%GG4) and invasive cribriform and/or intraductal carcinoma in GS 3+4=7 prostate cancer biopsies. We reviewed 1031 prostate cancer biopsies from the European Randomized Study of Screening for Prostate Cancer. In total 370 men had G3+4=7. The relation of invasive cribriform and/or intraductal carcinoma and %GG4 with biochemical recurrence-free survival (BCRFS) after radical prostatectomy (n=146) and radiation therapy (n=195) was analyzed using Cox regression. Invasive cribriform and/or intraductal carcinoma occurred in 7/121 (6%) patients with 1-10% GG4, 29/131 (22%) with 10-25%, and 52/118 (44%) with 25-50% GG4 (P

In Low-Tech Italian greenhouses, the adoption of more rational criteria in resources management would lead to significant economic and environmental advantages for producers. Reliable crop growth and evapotranspiration models, may allow real time assessment of water and nutrient plant requirements and the evaluation of the productive system efficiency, supporting decision-making processes for short, long and medium-term strategies. This paper presents the results of an experimental trial carried out in 2011, in the research facilities of the DISAAA-a at Pisa University, to set a cross-control method for the evaluation of the Water Use Efficiency (WUE) and of the real plant water requirements. A modified version of TOMGRO model was used to simulate Leaf Area Index (LAI) and total dry biomass (shoot and fruits) of three different cultivars of tomato (Solanum lycopersicum L.), grown in the same environmental conditions. For each cultivar, the hourly values of LAI provided by the TOMGRO model were used as input in the Baille equation for the estimation of the evapotranspiration (ET) rate, finding a significant agreement between simulated and measured ET values (R2= 0.8 on average). A good prediction of the WUE of each thesis was also obtained (R2>0.8), offering interesting elements for plant performance evaluation. Considering these evidences, a synthetic index (Estimated Biomass/ Estimated ET) may be used for a direct comparison between different scenarios.

Wild edible plants have been used in cooking since ancient times. Recently, their value has improved as a result of the scientific evidence for their nutraceutical properties. Sanguisorba minor Scop. (salad burnet) plants were hydroponically grown and two consecutive cuts took place at 15 (C1) and 30 (C2) days after sowing. An untargeted metabolomics approach was utilized to fingerprint phenolics and other health-related compounds in this species; this approach revealed the different effects of the two cuts on the plant. S. minor showed a different and complex secondary metabolite profile, which was influenced by the cut. In fact, flavonoids increased in leaves obtained from C2, especially flavones. However, other secondary metabolites were downregulated in leaves from C2 compared to those detected in leaves from C1, as evidenced by the combination of the variable important in projections (VIP score > 1.3) and the fold-change (FC > 2). The storage of S. minor leaves for 15 days as fresh-cut products did not induce significant changes in the phenolic content and antioxidant capacity, which indicates that the nutraceutical value was maintained. The only difference evidenced during storage was that leaves obtained from C2 showed a lower constitutive content of nutraceutical compounds than leaves obtained from C1; except for chlorophylls and carotenoids. In conclusion, the cut was the main influence on the modulation of secondary metabolites in leaves, and the effects were independent of storage.

Linseed (Linum usitatissimum L.) is becoming more and more important in the health food market as a functional food, since its seeds and oil represent a rich source of bioactive compounds. Its chemical composition is strongly correlated with, and dependent on, genetic characteristics. The aim of this study was to evaluate the variation in seed yield, oil content, fatty acid composition and secondary metabolite profiles between a low-linolenic linseed variety, belonging to the Solin-type group (Solal), and a high-linolenic traditional one (Bethune), cultivated, both as spring crops, in open field conditions of Central Italy. The achieved results pointed out the different behavior of the two varieties in terms of growth cycle, oil content, and some important yield components, such as capsule number per plant and thousand seed weight. There were also significant differences in seed composition regarding total phenols, total flavonoids, antioxidant activities as well as in carotenoid, tocopherol, and tocotrienol profiles between the two varieties. In particular, Solal was characterized by the greatest contents of oil, phenols, flavonoids, &alpha, and &delta, tocotrienol, together with the highest antioxidant activity. Bethune, on the contrary, showed the highest amounts of carotenoids (lutein and &beta, carotene). These results indicate a clear effect of the genetic characteristics on the biosynthesis of these secondary metabolites and, consequently, on the related antioxidant activity. Our findings suggest that the mutation process, responsible for the selection of the low-linolenic cultivar, is able to modify the biosynthetic pathways of carotenoids and phenolics.

Purpose: To develop and validate a robust and accurate registration pipeline for automatic contour propagation for online adaptive Intensity-Modulated Proton Therapy (IMPT) of prostate cancer using elastix software and deep learning. Methods: A three-dimensional (3D) Convolutional Neural Network was trained for automatic bladder segmentation of the computed tomography (CT) scans. The automatic bladder segmentation alongside the computed tomography (CT) scan is jointly optimized to add explicit knowledge about the underlying anatomy to the registration algorithm. We included three datasets from different institutes and CT manufacturers. The first was used for training and testing the ConvNet, where the second and the third were used for evaluation of the proposed pipeline. The system performance was quantified geometrically using the dice similarity coefficient (DSC), the mean surface distance (MSD), and the 95% Hausdorff distance (HD). The propagated contours were validated clinically through generating the associated IMPT plans and compare it with the IMPT plans based on the manual delineations. Propagated contours were considered clinically acceptable if their treatment plans met the dosimetric coverage constraints on the manual contours. Results: The bladder segmentation network achieved a DSC of 88% and 82% on the test datasets. The proposed registration pipeline achieved a MSD of 1.29 ± 0.39, 1.48 ± 1.16, and 1.49 ± 0.44 mm for the prostate, seminal vesicles, and lymph nodes, respectively, on the second dataset and a MSD of 2.31 ± 1.92 and 1.76 ± 1.39 mm for the prostate and seminal vesicles on the third dataset. The automatically propagated contours met the dose coverage constraints in 86%, 91%, and 99% of the cases for the prostate, seminal vesicles, and lymph nodes, respectively. A Conservative Success Rate (CSR) of 80% was obtained, compared to 65% when only using intensity-based registration. Conclusion: The proposed registration pipeline obtained highly promising results for generating treatment plans adapted to the daily anatomy. With 80% of the automatically generated treatment plans directly usable without manual correction, a substantial improvement in system robustness was reached compared to a previous approach. The proposed method therefore facilitates more precise proton therapy of prostate cancer, potentially leading to fewer treatment-related adverse side effects.

Purpose In the multicenter, phase 3, HYpofractionated irradiation for PROstate cancer trial, hypofractionated (HF) radiation therapy was compared with conventionally fractionated (CF) radiation therapy. In previous reports, we could not demonstrate the postulated superiority of hypofractionation in terms of relapse-free survival at 5 years. The frequent use of long-term androgen deprivation therapy might have had substantial effects on relapse-free survival. In the current analysis, we provide updated 7-year relapse-free survival outcomes. Methods and Materials We enrolled patients with intermediate- to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer. Patients were randomly assigned (1:1) to either HF (64.6 Gy in 19 fractions) or CF (78.0 Gy in 39 fractions) radiation therapy. Based on an estimated α/β ratio for prostate cancer of 1.5 Gy, the EQD2 was 90.4 Gy for HF versus 78.0 Gy for CF radiation therapy. The primary endpoint of the present analysis is relapse-free survival at 7 years. Results A total of 820 patients were enrolled, of whom 804 were assessable for the current evaluation (407 HF versus 397 CF). Median follow-up was 89 months (interquartile range, 83-99). Concomitant androgen deprivation therapy was prescribed for 537 (67%) of 804 patients for a median duration of 32 months (interquartile range, 10-44). Treatment failure at 7 years was reported in 220 (27.4%) of 804 patients, 107 (26.3%) in HF versus 113 (28.5%) in CF radiation therapy. Seven-year relapse-free survival was 71.7% (95% confidence interval [CI], 66.4-76.4) for HF versus 67.6% (95% CI, 62.0-72.5) for CF (P = .52). Overall survival was 80.8% (95% CI, 76.5-84.4) in HF versus 77.6% (95% CI, 73.0-81.5) in CF radiation therapy (P = .17). Conclusions The current results of 7-year relapse-free survival confirmed our previous findings that the hypothesized dose escalation in the HF arm did not translate to superior tumor control compared with the CF arm.

Introduction Sexual function can be impaired by all prostate cancer treatment modalities, but studies specifically addressing the impact of stereotactic body radiotherapy (SBRT) on sexual function are scarce. Aim To systematically evaluate sexual outcomes in patients treated by SBRT for prostate cancer and determine clinical factors associated with erectile dysfunction (ED). Methods A systematic review of the available literature was performed on PubMed/Medline, Scopus, and Cochrane Library databases in June 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Only articles providing data on baseline and post-treatment sexual function after SBRT (≥5 Gy/fraction) were included in this analysis (n = 12). Main Outcome Measure Sexual function deteriorates after SBRT of the prostate. Results Deterioration of sexual health was found, with Expanded Prostate Cancer Index Composite–26 sexual domain scores showing a median decrease of 9.2 at 12 months and a median decrease of the Sexual Health Inventory for Men subdomain score by 2.7 at 12 months (from baseline median value of 56.3 and 16, respectively). At 60 months, ED was reported by 26–55% of previously sexually functioning patients in 5 of the 12 studies. Clinical Implications ED affects ≤55% of previously sexually functioning patients at 5 years, as reported for other non-surgical treatment modalities. Strengths & Limitations This study enforced strict inclusion criteria of selected studies and exclusion of patients receiving concurrent androgen deprivation therapy. However, inconsistencies in the choice of assessment tool and definition of ED hamper a robust meta-analysis of pooled data. Conclusion Sexual function decline after SBRT for prostate cancer appears to be similar to other modalities and should be specifically addressed in future studies.

Wild edible plants have been used in cooking since ancient times. Recently, their value has improved as a result of the scientific evidence for their nutraceutical properties. Sanguisorba minor Scop. (salad burnet) plants were hydroponically grown and two consecutive cuts took place at 15 (C1) and 30 (C2) days after sowing. An untargeted metabolomics approach was utilized to fingerprint phenolics and other health-related compounds in this species, this approach revealed the different effects of the two cuts on the plant. S. minor showed a different and complex secondary metabolite profile, which was influenced by the cut. In fact, flavonoids increased in leaves obtained from C2, especially flavones. However, other secondary metabolites were downregulated in leaves from C2 compared to those detected in leaves from C1, as evidenced by the combination of the variable important in projections (VIP score &gt, 1.3) and the fold-change (FC &gt, 2). The storage of S. minor leaves for 15 days as fresh-cut products did not induce significant changes in the phenolic content and antioxidant capacity, which indicates that the nutraceutical value was maintained. The only difference evidenced during storage was that leaves obtained from C2 showed a lower constitutive content of nutraceutical compounds than leaves obtained from C1, except for chlorophylls and carotenoids. In conclusion, the cut was the main influence on the modulation of secondary metabolites in leaves, and the effects were independent of storage.

Androgen-deprivation therapy was shown to improve treatment outcome of external beam radiation therapy (EBRT) for locally advanced prostate cancer (PCa). DNA damage response (DDR) was suggested to play a role in the underlying mechanism, but conflicting results were reported. This study aims to reveal the role of the androgen receptor (AR) in EBRT-induced DDR and to investigate whether next-generation AR inhibitor apalutamide can radiosensitize PCa. PCa cell lines and tissue slices were treated with anti-androgen alone or combined with EBRT. The effect of treatments on cell growth, tissue viability, DDR, and cell cycle were investigated. RAD51 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) levels were determined by Western blotting. Homologous recombination (HR) capacity was measured with the directed repeats-green fluorescent protein (DR-GFP) assay. We report the radiosensitizing effect of anti-androgens, which showed synergism in combination with EBRT in AR-expressing tumor slices and cell lines. Moreover, a compromised DDR was observed in AR-expressing cells upon AR suppression. We found that AR inhibition downregulated DNA-PKcs expression, resulting in reduced non-homologous end-joining repair. DDR through HR was a secondary effect due to cell-cycle change. These data provide a mechanistic explanation for the combination regimen and support the clinical use of apalutamide together with EBRT for localized PCa patients.

In Europe, most greenhouse vegetable crops are grown in soil. Where soilless systems are used, apart from in The Netherlands, Belgium and France, they are mostly free-draining systems, in which nutrient solutions are not recirculated. Both soil-grown and free-draining soilless systems commonly have large nitrate (NO3−) leaching loss. Irrigation is a major contributing factor to NO3− leaching loss. Irrigation management of greenhouse vegetable crops needs to be improved to reduce the appreciable N loss to subterranean water and surface water bodies. This article reviews the state-of-the-art, of methods and tools that are available, or are being developed, to optimise irrigation management of both soil- and soilless-grown vegetable crops in greenhouses. Adaptions for greenhouse conditions and cropping cycles of the FAO56 approach to calculate crop water requirements are reviewed. Attention is paid to (i) the developments and suitability of various adaptations of the Penman–Monteith FAO56 equation and simpler equations to calculate reference crop evapotranspiration (ETO), and (ii) equations to calculate crop coefficient (Kc) values under greenhouse conditions, in which cropping cycles may differ appreciably from those of outdoor crops. The various classes of soil/substrate moisture sensors that have been used in greenhouse crops are reviewed, regarding their general suitability and practical use. Their use in both soil and substrate is considered, as are the effects of salinity and the use of some sensors to measure the salinity of the growing media. The use of various plant sensors with vegetable crops under greenhouse conditions is reviewed. The results of a survey that assessed, for greenhouse vegetable crops in Europe, the use of different (a) types of irrigation systems, and (b) irrigation management methods, for both soil and soilless production are presented. Following the revision of this information, recommendations are made regarding the scientific and practical value of the available tools and technologies to aid growers to optimise irrigation management of vegetable crops grown in greenhouses.

Introduction Hypofractionated radiotherapy could increase the radiobiological tumor dose for localized prostate cancer. The effects of hypofractionation on sexual function are not well known. Aim To compare sexual function in patients with prostate cancer treated with 78 Gy in 39 fractions of 2 Gy or 64.6 Gy in 19 fractions of 3.4 Gy. Methods In total, 820 men with intermediate- to high-risk T1b-T4NX-0MX-0 prostate cancer were enrolled in the phase III HYPRO trial (2007–2010) and randomized to conventional fractionation (39 × 2 Gy) or hypofractionation (19 × 3.4 Gy). Sexual function was assessed at baseline and at 6, 12, 24, and 36 months after treatment using the International Index of Erectile Function (IIEF). For this analysis, patients (n = 322) with a baseline assessment, at least one follow-up assessment, and no or short-term (6-month) androgen-deprivation therapy were included. Main Outcome Measures Mean IIEF domain scores were compared between treatments in the total population and the hormone-naïve population (n = 197) using the independent t-test. Incidences of severe erectile dysfunction (domain score < 11) at last follow-up were calculated in patients with partial or full baseline function. Binary logistic regression analyses were applied to calculate the odds ratio of hypofractionation vs conventional fractionation and to adjust for clinical factors. Results Median age was 71 years (interquartile range = 67–71) and median follow-up was 37 months (interquartile range = 25–38). Androgen-deprivation therapy was prescribed in 125 (39%). IIEF domain scores decreased after treatment but were comparable between treatment arms at baseline and during follow-up. Orgasmic function scores in hormone-naïve patients were significantly higher at 3 years after hypofractionation (4.08 vs 2.65, P = .031). In patients (n = 120) with partial or full baseline erectile function, the incidence of erectile dysfunction at last follow-up was 34.4% for hypofractionated treatment vs 39.3% for conventional treatment (adjusted odds ratio = 0.84, 95% CI = 0.37–1.90, P = .67). Conclusion No significant differences in erectile functioning between conventional and hypofractionated radiotherapy were found. Hormone-naïve patients reported significantly higher orgasmic function scores at 3 years after hypofractionation.

Summary Background Studies have reported a low α/β ratio for prostate cancer, suggesting that hypofractionation could enhance the biological tumour dose without increasing genitourinary and gastrointestinal toxicity. In the multicentre phase 3, HYpofractionated irradiation for PROstate cancer (HYPRO) trial, hypofractionated radiotherapy was compared with conventionally fractionated radiotherapy for treatment of prostate cancer. We have previously reported acute and late incidence of genitourinary and gastrointestinal toxicity; here we report protocol-defined 5-year relapse-free survival outcomes. Methods We did an open-label, randomised, phase 3 trial at seven Dutch radiotherapy centres. We enrolled patients with intermediate-risk to high-risk T1b–T4NX–N0MX–M0 localised prostate cancer, a prostate-specific antigen concentration of 60 μg/L or less, and a WHO performance status of 0–2. We used a web-based application to randomly assign (1:1) patients to either hypofractionated radiotherapy of 64·6 Gy (19 fractions of 3·4 Gy, three fractions per week) or conventionally fractionated radiotherapy of 78·0 Gy (39 fractions of 2·0 Gy, five fractions per week). Based on an estimated α/β ratio for prostate cancer of 1·5 Gy, the equivalent total dose in fractions of 2·0 Gy was 90·4 Gy for hypofractionation compared with 78·0 Gy for conventional fractionation. The primary endpoint was relapse-free survival. All analyses were done on an intention-to-treat basis in all eligible patients. The HYPRO trial completed recruitment in 2010 and follow-up is ongoing. This trial is registered with ISRCTN, number ISRCTN85138529. Findings Between March 19, 2007, and Dec 3, 2010, 820 patients were enrolled, of whom 804 were eligible and assessable for intention-to-treat analyses. Of these, 407 were assigned hypofractionated radiotherapy and 397 were allocated conventionally fractionated radiotherapy. 537 (67%) of 804 patients received concomitant androgen deprivation therapy for a median duration of 32 months (IQR 10–44). Median follow-up was 60 months (IQR 51–69). Treatment failure was reported in 169 (21%) of 804 patients, 80 (20%) in the hypofractionation group and 89 (22%) in the conventional fractionation group. 5-year relapse-free survival was 80·5% (95% CI 75·7–84·4) for patients assigned hypofractionation and 77·1% (71·9–81·5) for those allocated conventional fractionation (adjusted hazard radio 0·86, 95% CI 0·63–1·16; log-rank p=0·36). There were no treatment-related deaths. Interpretation Hypofractionated radiotherapy was not superior to conventional radiotherapy with respect to 5-year relapse-free survival. Our hypofractionated radiotherapy regimen cannot be regarded as the new standard of care for patients with intermediate-risk or high-risk prostate cancer. Funding Dutch Cancer Society.

Erectile dysfunction (ED) has been well recognized as a marker of increased cardiovascular risk for more than 15 years, especially in younger men. Early detection of ED represents an opportunity to intervene to decrease the risk of future cardiovascular events and limit the progression of ED severity. Evidence suggests there is a window of opportunity of 3 to 5 years from the onset of ED to subsequent cardiovascular events. This opportunity is usually missed if the onus is placed on the patient to seek care for his sexual problems. Unfortunately, these clear messages have not been incorporated into routine cardiovascular care. The reasons for these disparities within specialties are discussed in this article, in addition to management algorithms. Lifestyle modification is usually recommended as the first-line treatment to correct ED and lessen cardiovascular risk, but evidence suggests that this might be effective only in men without established cardiovascular comorbidities. In men with type 2 diabetes mellitus and established cardiovascular disease, lifestyle modification alone is unlikely to be effective. Cardiovascular medications are often associated with sexual dysfunction but changes in medication are more likely to be beneficial in men with milder recent-onset ED. A balanced view must be taken related to medication adverse events, taking into account optimal management of established cardiovascular disease. Testosterone deficiency has been associated with different metabolic disorders, especially metabolic syndrome and type 2 diabetes mellitus. Testosterone deficiency syndrome has been associated with an independent burden on sexual function globally and increased cardiovascular and all-cause mortality. Testosterone replacement therapy has been shown to improve multiple aspects of sexual function and, in some studies, has been associated with a decrease in mortality, especially in men with type 2 diabetes mellitus. Recent studies have suggested that phosphodiesterase type 5 inhibitors, the first-line medications to treat ED, could decrease cardiovascular and all-cause mortality, through multiple mechanisms, predominantly related to improved endothelial function.Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Purpose: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. Methods and Materials: Patients treated with 3D-CRT (n = 189) or IG-IMRT (n = 242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade >= 2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade >= 2 toxicities between both techniques, adjusting for other modifying factors. Results: The 5-year cumulative incidence of grade >= 2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P = .005), with significant reductions in proctitis (HR: 0.37, P = .047) and increased stool frequency (HR: 0.23, P= 2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P = .33). Other strong predictors (P= 2 late toxicity were baseline complaints, acute toxicity, and age. Conclusions: Treatment with IG-IMRT reduced the risk of late grade >= 2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution. (C) 2016 Elsevier Inc. All rights reserved.

Introduction: The diagnosis, treatment, and survivorship of cancer have a profound effect on the quality of life and psychological well-being of men and women. Indeed, the perturbation of sexual function because of neoplasm has far-reaching implications. Aims: To explore the prevalence, pathophysiology, and treatment of sexual issues in persons with cancer and offer evidence-based recommendations regarding optimal prevention and treatment strategies. Methods: A committee of multidisciplinary specialists was formed as part of the larger International Sexual Medicine Consultation working with urologic and sexual medicine societies over a 1-year period to review the result of chronic-illness management on sexual function and satisfaction. The aims, goals, data collection techniques, and report format were defined by a central committee. Main Outcomes Measures: Expert consensus was based on evidence-based medical and psychosocial literature review, extensive group discussion, and an open presentation with a substantial discussion period. Results: This summary evaluates contemporary literature concerning the prevalence, pathophysiology, and psychological impact of cancer diagnosis and treatment on sexual dysfunction. Evidence-based recommendations and guidelines for evaluation and management are presented. Conclusion: The diagnosis and treatment of cancer have a significant negative impact on sexual function and satisfaction. Comprehension of baseline sexual function, role of psychological supports, and available treatment options could attenuate the heavy burden of decreased sexual function. Copyright (C) 2016, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

textabstractAims: To investigate nail penetration enhancing effectiveness of a novel drug formulation and ingredients, 40% propylene glycol (PG) and 40 μM multifunctional photosensitizer (MFPS). Proposed formulation was proven effective in photodynamic treatment (PDT) of ex vivo fungal infections of human nails (onychomycoses) and indirectly also to weaken nail’s strength. Study Design: To directly proof the effect of the novel formulation on nail’s hardness Atomic Force Microscopy (AFM) was employed to measure small-distance forces. Based on indentations Young’s moduli of healthy and ex vivo onychomycosis nails were calculated before and after treatment with the novel formulation. Changes in young’s modulus can be related to changes in nail’s strength and thus formulation effectiveness. Additionally, AFM imaging was employed to study topographical / roughness changes resulting from the treatments to both nail types. Trichophyton mentagrophytes, representative for clinical onychomycosis, was chosen to induce nail infections.

Background and purpose: We evaluated dose distributions in the anorectum and its relation to acute gastrointestinal toxicities using dose surface maps in an image-guided (IG) IMRT and 3D-conformal radiotherapy (3D-CRT) population. Material and methods: For patients treated to 78 Gy with IG-IMRT (n = 260) or 3D-CRT (n = 215), for whom acute toxicity data were available, three types of surface maps were calculated: (1) total anorectum using regular intervals along a central axis with perpendicular slices, (2) the rectum next to the prostate, and (3) the anal canal (horizontal slicing). For each toxicity, an average dose map was calculated for patients with and without the toxicity and subsequently dose difference maps were constructed, 3D-CRT and IG-IMRT separately. P-values were based on permutation tests. Results: Dose distributions in patients with grade >= 2 acute proctitis were significantly different from dose distributions in patients without toxicity, for IG-IMRT and 3D-CRT. At the cranial and posterior rectal site, in areas receiving moderate dose levels (approximate to 25-50 Gy), dose differences up to 10 Gy were identified for IG-IMRT. For pain, cramps, incontinence, diarrhea and mucus loss significant differences were found as well. Conclusions: We demonstrated significant relationships between acute rectal toxicity and local dose distributions. This may serve as a basis for subsequent dose-effect modeling in IG-IMRT, and improved dose constraints in current clinical practice. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Globe artichoke is cultivated for its flower heads and as the source of pharmaceutical compounds from the leaves, whose extracts contain a high level of health-promoting compounds and show one of the highest antioxidant capacities reported for vegetables. The content and composition of such beneficial plant secondary metabolites may be greatly affected by cultivation variables, including plant genotype and mycorrhizal symbiosis. This study was carried out to gain knowledge on antioxidant activity, total phenols and chlorogenic acid levels in the leaves of two artichoke cultivars, Romanesco and Tema, as affected by six arbuscular mycorrhizal fungi (AMF) belonging to diverse genera, species and isolates. The six AMF showed significantly higher percentages of root colonization in Romanesco (46 %) than in Tema (32 %), and different colonization dynamics. The overall pooled data showed that in Romanesco the levels of total phenols increased by 35 %, chlorogenic acid by 67 % and antioxidant activity by 43 %, compared with Tema. The six AMF differentially affected such levels, with Claroideoglomus claroideum 22W3 as the only isolate producing significant increases compared with controls, for total phenols and chlorogenic acid, and with C. claroideum 22W3 and Funneliformis mosseae IMA1 as the isolates enhancing antioxidant activity, compared with controls. Moreover, a strong correlation was found between total phenols and antioxidant activity in the leaves of both artichoke cultivars. This work, comparing the highest number of diverse AMF studied so far in relation to their modulation of plant secondary metabolism, expanded our knowledge on their functional diversity and allowed the detection of the best performing symbionts to be utilized for obtaining artichoke leaves with enhanced health-promoting activities.

Prostate cancer heterogeneity and multifocality might result in different Gleason scores (GS) at individual biopsy cores. According to World Health Organisation/International Society of Urologic Pathology (WHO/ISUP) guidelines, the GS in each biopsy core should be recorded with optional reporting of overall GS for the entire case. We aimed to compare the clinicopathological characteristics and outcome of men with overall biopsy GS 3 + 4 = 7 with highest GS 3 + 4 = 7 (HI = OV) to those with highest GS 3 + 4 = 7 (HI OV).Prostate cancer biopsies from the European Randomised Study of Screening for Prostate Cancer (ERSPC) were revised according to WHO/ISUP 2014 guidelines (n = 1031). In total, 370 patients had overall GS 3 + 4 = 7, 60 of whom (16%) had had at least one biopsy core with GS 4 + 3 = 7 or 4 + 4 = 8. Men with higher GS than 3 + 4 (HI OV) in any of the cores had higher age, prostate-specific antigen (PSA) level, number of positive biopsies, percentage tumour involvement, percentage Gleason grade 4 and cribriform or intraductal growth (all P 0.05) than those with GS 3 + 4 = 7 at highest (HI = OV). In multivariable Cox regression analysis, including PSA, percentage positive biopsies and percentage tumour involvement, biochemical recurrence-free survival after radical prostatectomy (P = 0.52) or radiotherapy (P = 0.35) was not statistically different between both groups.Among patients with overall GS 3 + 4 = 7, those with highest GS 3 + 4 = 7 had worse clinicopathological features, but clinical outcome was not statistically significant. Therefore, the use of overall GS instead of highest GS for clinical decision-making is justified, potentially preventing overtreatment in prostate cancer patients.

BACKGROUND: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated.METHODS: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case-cohort design.RESULTS: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7-1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05-2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11-0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI:-0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose.CONCLUSION: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors.

The environmental performance of six green roof solutions currently available on the Italian market has been compared and a lack of information comes out, both on environmental and thermal issues that are necessary to run a consistent and specific assessment. Life Cycle Analysis (LCA) could support producers in designing more efficient and low-impact green roofs, selecting materials based on their environmental profile over their life cycle and taking into account potential reuse of recycle at the end of life. This paper presents an environmental assessment 'cradle to gate', based on a 1-m2 functional unit (FU), according to European Standard EN 15804:2012+A1:2013. Five different scenarios, based on different "U-value" limits according to D.M. 26/06/2016, have been defined to run the comparison. Outcomes are expressed in parameters describing environmental impact and resources use. The results show that, despite a large interest in green roofs, currently considered to be a sustainable and energy saving solution for both cold and warm climate, no specific information and data are in fact available for designers and LCA practitioners to assess the environmental and energy performance accurately. Moreover, the insulation layer is the primary responsible for both the energy and environmental performance of the green roof and therefore, taking into account the LCA profile of the insulation material during the design stage is a crucial step to guarantee a low-impact building. Moreover, the new vegetative substrates available on the market are generally presented as more sustainable when, in fact, LCA quarrels with that. Therefore, a comparison between 7 different media currently available on the market has been carried out; results have been significantly affected by a large lack of specific LCI data. © ISHS.

In Europe a number of procedures are used to assist growers and advisors to determine optimal N fertiliser recommendations. The implementation of European Union (EU) legislation is encouraging the adoption of fertiliser recommendation schemes. The most widely used schemes are those based on soil testing or on the use of indices that estimate the soil nitrogen supply. Soil testing approaches that are in use, particularly in NW Europe are the Nmin, KNS and N-Expert systems; the latter is operated as a computer-based decision support system (DSS). The comprehensive RB209 Fertiliser Manual of England and Wales uses soil N supply indices, but soil analysis can also be used. Nitrogen balance calculations are widely used throughout Europe and form part of the KNS and N-Expert systems, and a number of other DSSs. The N balance considers the various soil N sources and treats mineral N fertiliser as a supplemental N source. The EU-Rotate_N simulation model is a comprehensive and versatile tool, developed for diverse European conditions, that is useful for scenario analysis simulations to stakeholders. Various DSS have been developed in different European countries, with different levels of complexity. There are a number of different DSS that calculate N fertiliser recommendations for particular cropping systems; some DSS calculate the requirements for other nutrients, and some also do so for irrigation which is particularly useful where fertigation is used. Sap analysis has been shown to be sensitive to crop nutrient status, for N and some other nutrients; currently, there is renewed interest in sap analysis. Proximal optical sensors are a promising approach for N management.

Purpose Testicular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk. Methods Solid SMN risk was evaluated in a multicenter cohort comprising 5,848 1-year survivors treated for TC before age 50 years between 1976 and 2007. SMN incidence was compared with cancer incidence in the general population. Treatment-specific risks were assessed using multivariable regression in a case-cohort design. Results After a median follow-up of 14.1 years, 350 solid SMNs were observed, translating into a 1.8-fold (95% CI, 1.6-2.0) increased risk compared with general population rates. Solid SMN risk was increased in patients with seminoma and those with nonseminoma (standardized incidence ratio, 1.52 and 2.21, respectively). Patients with nonseminoma experienced increased risk of SMNs of the thyroid, lung, stomach, pancreas, colon, and bladder and of melanoma and soft tissue sarcoma, whereas those with seminoma experienced increased risk of SMNs of the small intestine, pancreas, and urinary bladder. The 25-year cumulative incidence of solid SMNs was 10.3% (95% CI, 9.0% to 11.6%). In multivariable analysis, platinum-based chemotherapy was associated with increased risk of a solid SMN (hazard ratio [HR], 2.40; 95% CI, 1.58 to 3.62), colorectal SMN (HR, 3.85; 95% CI, 1.67 to 8.92), and noncolorectal GI SMN (HR, 5.00; 95% CI, 2.28 to 10.95). Receipt of platinum 400 to 499 and ≥ 500 mg/m2 increased solid SMN risk compared with surgery only (HR, 2.43; 95% CI, 1.40 to 4.23 and HR, 2.42; 95% CI, 1.50 to 3.90, respectively), whereas risk was not significantly increased with lower doses (HR, 1.75; 95% CI, 0.90 to 3.43). The HR of a GI SMN increased by 53% (95% CI, 26% to 80%) per 100 mg/m2 of platinum-containing chemotherapy. The HR of an infradiaphragmatic SMN increased by 8% per Gray of radiation dose administered (95% CI, 6% to 9%; P < .001). Conclusion Radiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.