design and performance analysis of a zero energy settlement in greece

Zero-energy and zero-carbon buildings would be a huge opportunity for contrasting the climatic changes and, more in general, the deterioration of the microclimate inside and around cities. About it, a question appears compulsory: are zero-energy and zero-carbon concepts applicable at urban scale? This paper tries to answer to this question, by discussing the possible effects of the application of appropriate city planning techniques when a new settlement is designed. An integrated approach to urban planning is applied to a case study, for promoting the design of buildings with very low (or zero) energy needs, characterized by high indoor comfort conditions, by taking into consideration whole city areas, with different kinds of services. Passive heating, cooling and daylighting techniques have been combined, as well as the integration of renewable sources, in order to minimize the energy demand and environmental impact, for having a sustainable 'urban balance' and, in general, a sustainable urban growth. As real case study, the design of the holiday village 'Olympiad' is presented; it should be built in an unstructured seaside area in Greece. Several indexes are introduced to evaluate the global sustainability of the settlement, through the application of the definition of 'on-grid ZEB', with reference to each building as well as for the entire village. This kind of research could help city planners for a growth inspired to general goals of urban sustainability

Cultural adaptation and psychometric evaluation of the Swedish version of the Reproductive Concerns After Cancer (RCAC) scale

BACKGROUND: Reproductive concerns are common among young cancer survivors and include worries related to different aspects of fertility and parenthood. The Reproductive Concerns After Cancer (RCAC) scale is an 18-item scale with six dimensions, developed to capture a variety of such concerns. The aim of the present study was to describe the cultural adaptation of the RCAC scale into Swedish and evaluate its psychometric properties among young women who have undergone treatment for cancer. METHODS: The RCAC was forward translated from English into Swedish and assessed for cultural adaptation based on a two-panel approach followed by cognitive interviews with the target group. For the psychometric evaluation, a Swedish cohort of 181 female young adult breast cancer survivors completed a survey including the RCAC scale approximately 1.5 years post-diagnosis. Psychometric properties were examined by analyses of construct validity (confirmatory factor analysis and convergent validity), data quality (score distribution, floor and ceiling effects), reliability and known-groups validity. RESULTS: The confirmatory factor analysis yielded an acceptable fit (RMSEA 0.08, SRMR 0.09, CFI 0.92). Convergent validity was demonstrated by a negative correlation of moderate size (- 0.36) between the RCAC total score and the emotional function scale of the EORTC QLQ-C30. Reliability measured with Revelle Ω total was satisfactory (0.73-0.92) for five of the dimensions, and poor for the dimension Becoming pregnant (Revelle Ω total = 0.60); Cronbach's alpha showed a similar pattern. Known-groups validity was indicated by significant RCAC mean score differences (MD), reflecting more concerns among women with a certain (MD 4.56 [95% CI 3.13 to 5.99]) or uncertain (MD 3.41 [95% CI 1.68 to 5.14]) child wish compared to those with no wish for (additional) children. CONCLUSION: The translation and cultural adaptation of the Swedish RCAC has resulted in a scale demonstrating construct and known-groups validity, and satisfactory reliability for five of six dimensions. The dimension Becoming pregnant showed non-optimal internal consistency and should undergo further evaluation. The Swedish RCAC is recommended to be used in research settings for measurement of concerns related to fertility and parenthood in young women with cancer

Paclitaxel chemotherapy and vascular toxicity as assessed by flowmediated and nitrate-mediated vasodilatation

Background: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant proinflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. Methods: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-α and IL-6 before and after chemotherapy. Results: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p=0.005) and NMD (p=0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p=0.045), whereas NMD was not affected (p=0.421). Although TNF-α and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. 82 Conclusion: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markersΕισαγωγή: Η αντινεοπλασματική δράση της Πακλιταξέλης βασίζεται στη προαγωγή της ανώμαλης συνάθροισης μικροσωληνίσκων αλλά επίσης θεωρείται ότι έχει σημαντικές προ-φλεγμονώδεις και αντι-αγγειογενετικές δράσεις in vivo και επομένως μπορεί να προκαλέσει αγγειακή δεισλειτουργία. Μέθοδοι: Μελετήσαμε 27 γυναίκες που έλαβαν συνδυασμούς που περιείχαν Πακλιταξέλη για καρκίνο μαστού ή ωοθηκών. Η ομάδα ελέγχου αντιπροσωπευόταν από 10 γυναίκες με καρκίνο τραχήλου μήτρας που έλαβαν χαμηλές δόσεις Σισπλατίνης εβδομαδιαίως ως ευαισθητοποιό. Μετρήσαμε την ενδοθηλιοεξαρτώμενη (FMD) και τη μη-ενδοθηλιοεξαρτώμενη αγγειοδιαστολή (NMD) της δεξιάς βραχιονίου αρτηρίας με υπερήχους καθώς και τα επίπεδα των φλεγμονωδών κυτταροκινών TNF-α και IL-6 πριν και μετά τη χημειοθεραπεία. Αποτελέσματα: Οι ασθενείς που έλαβαν Πακλιταξέλη με μία Ανθρακυκλίνη είχαν την πιο αξιοσημείωτη μείωση της FMD (p=0,005) και της NMD (p=0,027). Mία αξειοσημείωτη μείωση παρατηρήθηκε επίσης στις ασθενείς που έλαβαν εβδομαδιαία Πλατίνα (p=0,045) ενώ η ΝMD δεν επηρεάστηκε (p=0,421). Αν και τα επίπεδα των TNF-α και IL-6 ήταν διαφορετικά μεταξύ των ομάδων μετά τη θεραπεία, δεν παρατηρήθηκαν σημαντικές διαφορές των δύο δεικτών πριν και μετά τη θεραπεία. 80 Συμπεράσματα: Η θεραπεία με συνδυασμούς που περιέχουν Πακλιταξέλη βλάπτει την ενδοθηλιακή λειτουργία in vivo, όμως η βλάβη αυτή δεν σχετίζεται με τα επίπεδα στον ορό των δεικτών φλεγμονή

Targeting angiogenesis in head and neck cancer

Angiogenesis is a crucial step in tumor growth and metastasis. Head and neck squamous cell carcinomas (HNSCC) highly express angiogenesis factors, such as vascular endothelial growth factor (VEGF), which are associated with patient prognosis. Antiangiogenesis agents can potentially modulate tumor microenvironment and induce radiosensitivity and chemosensitivity. In this review, we discuss the molecular mechanisms underlying angiogenesis involved in HNSCC, preclinical data with antiangiogenesis agents as well as potential predictive biomarkers. We also review novel therapies under investigation and summarize the results of clinical trials using antiangiogenesis agents alone or in combination with conventional therapies in HNSCC. (C) 2015 Elsevier Ltd. All rights reserved

Investigating the Role of CTCs with Stem/EMT-like Features in Metastatic Breast Cancer Patients Treated with Eribulin Mesylate

We herein aimed to assess the effect of eribulin mesylate on the cancer stem cell (CSC)/EMT-like phenotype of CTCs, and to investigate the prognostic role of CTC detection and monitoring for eribulin-treated BC patients. Peripheral blood was obtained at baseline (n = 42 patients) and 8 days after treatment initiation (C1D8: n = 22), and on disease progression (PD: n = 26). PBMCs cytospins were immunofluorescently stained for Cytokeratins/ALDH1/TWIST1/DAPI and analyzed via Ariol microscopy. CTCs were detected in 33.3%, 27.3%, and 23.1% of patients at baseline, C1D8, and PD, respectively. Accordingly, partial-EMT+ CTCs represented 61.3%, 0%, and 37.5% of total CTCs, whereas the CSC-like phenotype was consistently expressed by 87.5%, 75%, and 91.7% of CTCs at the respective time points. Interestingly, the CSC+/partial-EMT+ subset prevailed at baseline, but it was eradicated on C1D8 and resurged again during PD. CTC detection at baseline was associated with reduced PFS (p = 0.007) and OS (p = 0.005), and was an independent risk factor for death (HR: 3.779, p = 0.001; multivariate analysis). The CSC+/partial-EMT+ CTCs emerged as the only subset with adverse prognostic significance, while CTC monitoring during eribulin therapy improved the prediction of disease progression. These results indicate that resistant CTC subsets persevere eribulin treatment and highlight the prognostic implications of CTC analyses for eribulin-treated BC patients

Pathways and targets in hepatocellular carcinoma

Expert Rev. Anticancer Ther. 12(10), 1347-1357 (2012) The incidence of hepatocellular carcinoma (HCC) has been rising in several western low-incidence areas over the past decade. The purpose of this review was to summarize the current knowledge on the ‘state of the art’ management of HCC focusing on targeted systemic therapies. The information for this review was compiled by searching the PubMed and MEDLINE databases for articles published until 1 June 2012. Cytotoxic chemotherapy has failed to affect outcome of HCC. Treatment with sorafenib is associated with survival gain in HCC but the responses are not durable. In addition, sorafenib is associated with substantial dermatologic and gastrointestinal toxicity. In this review, the authors summarize molecular targets and signal transduction pathways in HCC and provide an update of published and ongoing studies. Many targeted agents against angiogenesis, Ras/Raf/MAPK, EGF receptor, PI3K/AKT/mTOR, HGF/Met and IGF/IGF receptor are being tested in clinical trials

TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications

TLR4 and pSTAT3 are key players in cancer inflammation and immune evasion; however, their role in the peripheral blood (PB) is largely unexplored. Herein we evaluated their expression in the circulating tumor cells (CTCs) and peripheral-blood mononuclear cells (PBMCs) of patients with early (n = 99) and metastatic (n = 100) breast cancer (BC). PB samples obtained prior to adjuvant and first-line therapy, were immunofluorescently stained for Cytokeratins/TLR4/pSTAT3/DAPI and analyzed via Ariol microscopy. TLR4+ CTCs were detected in 50% and 68% of early and metastatic CTC-positive patients, respectively, and pSTAT3+ CTCs in 83% and 68%, respectively. In metastatic patients, CTC detection was associated with a high risk of death (HR: 1.764, p = 0.038), while TLR4+ CTCs correlated with a high risk of disease progression (HR: 1.964, p = 0.030). Regarding PBMCs, TLR4 expression prevailed in metastatic disease (p = 0.029), while pSTAT3 expression was more frequent in early disease (p = 0.014). In early BC, TLR4 expression on PBMCs independently predicted for high risk of relapse (HR: 3.549; p = 0.009), whereas in metastatic BC, TLR4+/pSTAT3− PBMCs independently predicted for high risk of death (HR: 2.925; p = 0.012). These results suggest that TLR4/pSTAT3 signaling on tumor- and immune-cell compartments in the PB could play a role in BC progression, and may hold independent prognostic implications for BC patients

TRPV4 Inhibition Exerts Protective Effects Against Resistive Breathing Induced Lung Injury

Introduction: TRPV4 channels are calcium channels, activated by mechanical stress, that have been implicated in the pathogenesis of pulmonary inflammation. During resistive breathing (RB), increased mechanical stress is imposed on the lung, inducing lung injury. The role of TRPV4 channels in RB-induced lung injury is unknown. Materials and Methods: Spontaneously breathing adult male C57BL/6 mice were subjected to RB by tracheal banding. Following anaesthesia, mice were placed under a surgical microscope, the surface area of the trachea was measured and a nylon band was sutured around the trachea to reduce area to half. The specific TRPV4 inhibitor, HC-067047 (10 mg/kg ip), was administered either prior to RB and at 12 hrs following initiation of RB (preventive) or only at 12 hrs after the initiation of RB (therapeutic protocol). Lung injury was assessed at 24 hrs of RB, by measuring lung mechanics, total protein, BAL total and differential cell count, KC and IL-6 levels in BAL fluid, surfactant Protein (Sp)D in plasma and a lung injury score by histology. Results: RB decreased static compliance (Cst), increased total protein in BAL (p < 0.001), total cell count due to increased number of both macrophages and neutrophils, increased KC and IL-6 in BAL (p < 0.001 and p = 0.01, respectively) and plasma SpD (p < 0.0001). Increased lung injury score was detected. Both preventive and therapeutic HC-067047 administration restored Cst and inhibited the increase in total protein, KC and IL-6 levels in BAL fluid, compared to RB. Preventive TRPV4 inhibition ameliorated the increase in BAL cellularity, while therapeutic TRPV4 inhibition exerted a partial effect. TRPV4 inhibition blunted the increase in plasma SpD (p < 0.001) after RB and the increase in lung injury score was also inhibited. Conclusion: TRPV4 inhibition exerts protective effects against RB-induced lung injury