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Summarization: Alternative tourism has gained considerable interest among consumers and enterprises in the tourism sector, creating new opportunities for providing high quality and innovative tourist services, while contributing to sustainable development. The Internet plays a key role as a tool for promoting alternative tourism. Motivated by this, this article presents an original research on the evaluation of the content features of the websites of enterprises involved with alternative tourism services in the region of Chania, Greece. The sample consists of 28 websites evaluated over 11 performance criteria through the ELECTRE III multicriteria method. The websites are ranked in a benchmarking context and the results of the evaluation are used to identify the most successful practices, as well as the website features that require improvements for the enterprises to take advantage of the opportunities that arise in the new era of technological innovation in the tourism sector. Presented on: IEEE Transactions on Engineering Management

In this work, the optical properties of red-light emitting materials used for active layers in functional red OLED devices were researched. The investigated materials are: a synthesized lab scale complex vinyl-quinoline pyridine homopolymer with Ir P[QPy-Ir-(PPy)2], as well as two commercially supplied materials, Poly[2-methoxy-5-(3′,7′-dimethyloctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) and Poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV). The samples were spin-coated on ITO/glass substrates. The characterization of the materials was carried out via Spectroscopic Ellipsometry (SE), Photoluminescence Spectroscopy (PL) and Electroluminescence Spectroscopy (EL). Through SE analysis the film thickness, the optical properties and the dielectric function were obtained. PL and EL spectra were derived and evaluated in terms of the emission profile and characteristics of the different photoactive materials. Finally, the colour stability and selectivity of each material were determined, and a comparative study of the red-light emitting materials was conducted.

White Organic Light-Emitting Diodes (WOLEDs) have attracted an enormous interest because they can be implemented in numerous lighting applications as next-generation light sources. In this work, terpolymers bearing blue, yellow and red chromophores are used for the fabrication of WOLED devices. These systems provide easy tuning of white color by changing weight ratios between the chromophores. The optical and opto-electronic characterization is carried out by near infrared–visible-far ultraviolet (NIR–Vis–FUV) Spectroscopic Ellipsometry (SE), Photoluminescence (PL), and Electroluminescence (EL), whereas the structural characterization is achieved by Atomic Force Microscopy (AFM), to provide valuable information toward the optimization and functionalization of these WOLED devices.

Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. Production of the 70 kDa heat shock protein (HSP70) is up-regulated to protect proteins from degradation. Sequestosome-1 (p62) binds to altered proteins and the p62-protein complex is degraded by autophagy. P62 is also a regulator of intracellular kinase activity and cell differentiation. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSP70 and a decrease in intracellular p62. In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSP70 and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSP70 levels were 79.3 ng/ml in PBMCs from women with a malignant lesion as opposed to 44.2 ng/ml in controls (p = 0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (p

Background Monitoring seasonal influenza Vaccine Effectiveness (VE) is key to inform vaccination strategies and sustain uptake. Pooling data across multiple seasons increases precision and allows for subgroup analyses, providing more conclusive evidence. Our aim was to assess VE against hospitalization with laboratory-confirmed influenza in Greece over six seasons, from 2013 to 2014 to 2018–2019, using routinely collected surveillance data. Methods Swab samples from hospitalized patients across the country were tested for influenza by RT-PCR. We used the test-negative design, with patients testing positive for influenza serving as cases and those testing negative serving as controls. VE was calculated as one minus the Odds Ratio (OR) for influenza vaccination, estimated by mixed-effects logistic regression and adjusted for age, sex, hospitalization type (being in intensive care or not), time from symptom onset to swabbing, and calendar time. Stratified estimates by age and hospitalization type were obtained, and also subgroup estimates by influenza type/subtype and season. Antigenic and genetic characterization of a subset of circulating influenza strains was performed. Results A total of 3,882 test-positive cases and 5,895 test-negative controls were analyzed. Across all seasons, adjusted VE was 45.5% (95% CI: 31.6–56.6) against all influenza, 62.8% against A(H1N1)pdm09 (95% CI: 40.7–76.7), 28.2% against A(H3N2) (95% CI: 12.0–41.3) and 45.5% against influenza B (95% CI: 29.1–58.1). VE was slightly lower for patients aged 60 years and over, and similar between patients hospitalized inside or outside intensive care. Circulating A(H1N1)pdm09 and B strains were antigenically similar to the vaccine strains, whereas A(H3N2) were not. Conclusion Our results confirm the public health benefits from seasonal influenza vaccination, despite the suboptimal effectiveness against A(H3N2) strains. Continued monitoring of VE is essential, and routinely collected surveillance data can be valuable in this regard.

Background: Preclinical and clinical studies suggest that trastuzumab resistance in HER2+ BC is mediated by cross-activation of alternative signaling pathways. Computational analysis and pooled whole-genome RNAi screens in HER2 transformed BC cell lines identified the IL6/JAK2/STAT3 axis as a master regulator pathway. The combination of trastuzumab plus ruxolitinib, a JAK1/JAK2 inhibitor, demonstrated synergistic tumor growth inhibition in mouse xenografts of HER2 transformed BC cell lines. These data provide the rationale for studying the efficacy of ruxolitinib and trastuzumab in a phase I/II trial. Design: This is an investigator-initiated, multi-center, open-label, phase I/II trial of ruxolitinib plus trastuzumab in patients (pts) with HER2+ MBC who have progressed on >2 HER2-directed therapies in the metastatic setting (including trastuzumab, pertuzumab and T-DM1, unless pt refusal). The phase I is an adaptive design with 10 pts to determine the recommended phase II dose (RP2D: 25 mg po BID, SABCS 2017). Phase II is a non-randomized open-label trial of 30 pts with trastuzumab plus ruxolitinib to compare progression free survival (PFS) against historical data with single-agent HER2-targeted therapy in HER+ MBC (Blackwell JCO 2010). The study was powered to detect a difference in median PFS of 8 weeks versus 13 weeks. Response was assessed by imaging every 9 weeks. Results: We accrued 28 pts from 10/14-8/18 and stopped early due to slow accrual. Of the 27 evaluable pts, 11 were in the phase I, of which 10 pts received 25 mg po BID (RP2D). Thus, 26 pts are included in the phase 2 study (pre-specified). Of the evaluable pts, the median age was 56 (range 32 - 77). Of these, 24 pts were postmenopausal (92%), 15 (58%) were estrogen receptor positive, and 24 (92%) had measurable disease, including 8 (33%) in lung and 4 (15%) in liver. The median number of prior lines of therapy in the metastatic setting was 4 (range: 2-9). Twenty-three pts (88.5%) received prior pertuzumab and 25 (96.1%) received prior T-DM1. As of 6/24/19, 2 pts remain on therapy at 46 and 72 weeks of follow-up. Twenty evaluable pts came off study due to progression, 3 due to death from disease, and 1 for adverse events. The median PFS was 10.7 weeks (95% CI: 7.1-15.1). The 6-month PFS is 21% (7%, 40%). The most common treatment-related adverse events (AEs) were hematologic [anemia 13 (50%), neutropenia 10 (38%), thrombocytopenia 8 (31%)], fatigue 9 (35%), aspartate aminotransferase increase 4 (15%) and diarrhea 4 (15%). The most common grade 3 AEs were anemia 7 (27%), and neutropenia 6 (23%). Grade 4 or higher events were not observed. Response data in pts with measurable disease will be presented at SABCS. Conclusion: Ruxolitinib plus trastuzumab was a well-tolerated regimen that does not include cytotoxic chemotherapy. While the combination did not achieve the primary endpoint (median PFS), there was 6-month PFS of 21% in this heavily pre-treated HER2+ MBC population. Ongoing analyses will be done to determine factors that predict clinical benefit. Citation Format: Kevin Kalinsky, Shing Lee, Amy Tiersten, Della F Makower, Tessa Cigler, Lauren Franks, Prabhjot Mundi, Dow-Chung Chi, Lauren Blumberg, Naomi Sender, Magdalena Galazyn, Kristina Hosi, Anupama Goel, Paula Klein, Eleni Andreopoulou, Joseph Sparano, Katherine D Crew, Andrea Califano, Jose Silva, Dawn L Hershman. Phase I/II trial of ruxolitinib in combination with trastuzumab in HER2+ metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-32.

The purpose of this study was to examine the implementation of Total Quality Management (TQM) as a business strategy in the Greek food and drink industry, along with the examination of the Information Technology (IT) adoption in the field. A research project was carried out in the sector companies based in Greece, using the questionnaire method. Findings showed a strong relation between IT implementation and impact of IT on TQM. Company size also seemed to affect TQM implementation, and the majority of IT implementation constructs, while company performance was not significant in terms of net profit margin and value added per employee.

This article, which is based on the science of informatics and environmental technologies, deals with the implementation of informatics in environmental science and practice. It focuses on web-based GIS spatial data sharing application system design and its development, which records and represents specific environmental information with emphasis on habitats and land cover. The system development was made by using JavaScript, PHP as programming languages and Google Maps API. The application provides centralized environmental information with habitats and land cover. It addresses ordinary users and scientists, that not only have the willing to expand their knowledge in the field but also they have the privilege to explore the research area over the map. The users can render the overlay information of spatial habitat and land cover data layers, execute zooming, panning, and information querying functions. Its aim is to offer, to any interested citizen, scientist or organization, direct and reliable environmental information.

This paper presents “e-praxis”, a Web-based Decision Support System (DSS), to assist the land Characterization Acts (CA) issuing process, performed by the Greek Forest Service (GFS). The issue under investigation is the characterization of specific or wider land areas as sylvan (forest ecosystem in general) or not, based on the applicable legislation and the fundamental principles of Forest Ecology. The proposed DSS is a web application that bases its operation and functionality on a model built for the decoding of the relevant Forest Legislation and utilizes the “Rule-Based Reasoning” technique for the design and implementation of the decision model. Programming languages such as PHP, HTML and JavaScript were employed for the development of the application. The main goal of the DSS is the simplification -and to the possible extent - automation of the process together with the reduction of the required examination time. “E-praxis” also aims to document the decision process based on objective criteria so as to combat bureaucracy and potential corruption. The use of the application by the GFS can save time that can be committed to other significant tasks and strengthen the objectivity in decision making. The proposed DSS could also be exploited as a consultation tool for freelance foresters-scholars, be used as a training tool for newly appointed foresters of the GFS and as an educational tool for Forestry and Legal sciences students.

There is a clinical need to predict sensitivity of metastatic hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer to endocrine therapy, and targeted RNA sequencing (RNAseq) offers diagnostic potential to measure both transcriptional activity and functional mutation. We developed the SETER/PR index to measure gene expression microarray probe sets that were correlated with hormone receptors (ESR1 and PGR) and robust to preanalytical and analytical influences. We tested SETER/PR index in biopsies of metastastic HR+/HER2− breast cancer against the treatment outcomes in 140 patients. Then we customized the SETER/PR assay to measure 18 informative, 10 reference transcripts, and sequence the ligand-binding domain (LBD) of ESR1 using droplet-based targeted RNAseq, and tested that in residual RNA from 53 patients. Higher SETER/PR index in metastatic samples predicted longer PFS and OS when patients received endocrine therapy as next treatment, even after adjustment for clinical-pathologic risk factors (PFS: HR 0.534, 95% CI 0.299 to 0.955, p = 0.035; OS: HR 0.315, 95% CI 0.157 to 0.631, p = 0.001). Mutated ESR1 LBD was detected in 8/53 (15%) of metastases, involving 1−98% of ESR1 transcripts (all had high SETER/PR index). A signature based on probe sets with good preanalytical and analytical performance facilitated our customization of an accurate targeted RNAseq assay to measure both phenotype and genotype of ER-related transcription. Elevated SETER/PR was associated with prolonged sensitivity to endocrine therapy in patients with metastatic HR+/HER2− breast cancer, especially in the absence of mutated ESR1 transcript., SCOPUS: ar.j, info:eu-repo/semantics/published

Interactive technologies enable dancers to control the music in real-time with their movement. This paper presents the design and development of a model which takes as input a dancer’s movement and outputs music, structurally related to dance, with the use of machine learning techniques. Both the technical and artistic aspects of the model development are described in detail. In particular, the paper compares the use of machine learning techniques to traditional coding, in interactive dance and music applications. Moreover, it describes the significant discrimination between movement sonification and dance musification and explains why the model presented here falls into the second category. Special focus is given to the implications of the COVID-19 restrictions regarding the established collaboration with the dancer.

Purpose: National Comprehensive Cancer Network guidelines recommend delivery of adjuvant chemotherapy in node-negative triple negative breast cancer (TNBC) if the tumor is > 1 cm and consideration of adjuvant chemotherapy for T1b but not T1a disease. These recommendations are based upon sparse data regarding the role of adjuvant chemotherapy in T1a and T1b node-negative TNBC. Our objective was to clarify the benefits of chemotherapy for patients with T1N0 TNBC, stratified by tumor size.Methods: We performed a retrospective analysis of survival outcomes in an IRB-approved prospectively-maintained database of TNBC patients treated at two academic institutions in the United States from 1999-2018. Primary tumor size, histology, and nodal status were based upon definitive surgical pathology. Mean follow-up was 5.3 years.Results: 756 TNBC cases were analyzed; 258 T1N0 TNBC patients were identified. Adjuvant chemotherapy was delivered to 30.5% of T1a, 64.7% T1b, and 83.9% T1c (p < 0.0001). Factors associated with delivery of adjuvant chemotherapy were age, histology, high-grade disease, and postoperative adjuvant radiation therapy. At a mean follow-up of 5.3 years, increase in overall survival was associated with use of chemotherapy in patients with T1c disease (93.2% v. 75.2% p = 0.008) but not in those with T1a (100% v. 100% p = 0.3778) or T1b (100% v. 95.8% p = 0.2362) disease.Conclusion: Our data support current guidelines indicating benefit from adjuvant chemotherapy in node-negative TNBC associated with T1c tumors but excellent outcomes were observed in cases of T1a and T1b disease, regardless of whether adjuvant chemotherapy was delivered.

Background: Peripheral blood mononuclear cells (PBMCs) respond to altered physiological conditions to alleviate the threat. The inducible 70kDa heat shock protein (HSPA1A) protects proteins from degradation. Autophagy is an intracellular process that removes damaged proteins and recycles their components to the cytoplasm. Sequestosome-1 (p62) is a protein consumed during autophagy. We hypothesized that the PBMC response to a malignant breast mass involves elevated production of HSPA1A and a decrease in intracellular p62.Methods: In this study 46 women had their breast mass excised. PBMCs were isolated and intracellular levels of HSPA1A and p62 were quantitated by ELISA. Differences between women with a benign or malignant breast mass were determined. Results: A breast malignancy was diagnosed in 38 women (82.6%) while 8 had a benign lesion. Mean intracellular HSPA1A levels were 79.3 ng/ml in PBMCs from women with a malignant lesion and 44.2 ng/ml in controls (p=0.04). The mean PBMC p62 level was 2.3 ng/ml in women with a benign breast lesion as opposed to 0.6 ng/ml in those with breast cancer (pConclusion: Intracellular HSPA1A and p62 levels in PBMCs differ between women with a malignant or benign breast lesion. These measurements may be of value in the preoperative triage of women with a breast mass.

Purpose: Preclinical data demonstrate STAT3 as an important regular in HER2+ tumors, and disruption of the IL6-JAK2-STAT-S100A8/S100A9 signaling cascade reduces HER2+ cell viability. Ruxolitinib is an FDA approved inhibitor of JAK1 and JAK2. We performed a phase I/II trial investigating the safety and efficacy of the combination of trastuzumab and ruxolitinib in patients with trastuzumab-resistant metastatic HER2+ breast cancer. Methods: Patients with metastatic HER2+ breast cancer progressing on at least 2 lines of HER2-directed therapy were eligible. The phase I portion determined the tolerable dose of ruxolitinib in combination with trastuzumab. The primary objective of the phase II was to assess the progression free survival (PFS) of the combination of ruxolitinib plus trastuzumab compared to historical control. Results: Twenty-eight patients were enrolled, with a median number of prior therapies of 4.5. Ruxolitinib 25mg twice daily was the recommended phase II dose with no DLTs. Of 26 evaluable patients in phase II, the median PFS was 8.3 weeks (95% CI: 7.1, 13.9). Among the 14 patients with measurable disease, 1 patient had a partial response and 4 patients had stable disease. Most of the adverse events were hematologic.Conclusion: While well-tolerated with a strong preclinical rationale, the combination of ruxolitinib and trastuzumab did not lead to an improvement in PFS compared to historical control in patients with trastuzumab-resistant metastatic HER2+ breast cancer.

Purpose: As monotherapies, eribulin (chemotherapy) and pembrolizumab (immunotherapy) have shown promise for patients with metastatic triple-negative breast cancer (mTNBC). This phase Ib/II study examined eribulin plus pembrolizumab as a potential mTNBC treatment in first-line and later-line settings. Patients and Methods: In this open-label, single-arm, phase Ib/II study, eligible patients had mTNBC, measurable disease, and ≤2 prior systemic anticancer therapies in the metastatic setting. Patients were enrolled by number of prior systemic anticancer therapies (stratum 1: 0 vs stratum 2: 1–2) in the metastatic setting and further analyzed by tumor programmed death-ligand 1 (PD-L1) expression status. All patients received intravenous eribulin 1.4 mg/m2 on day 1 and day 8, plus intravenous pembrolizumab 200 mg on day 1, of 21-day cycles. The primary objectives were the safety, tolerability, and objective response rate (ORR) of this combination. Results: The study included 167 patients (phase Ib, n = 7; phase II, n = 160). The most common treatment-emergent adverse events were fatigue (66%), nausea (58%), peripheral sensory neuropathy (41%), alopecia (40%), and constipation (37%). ORRs were 25.8% [95% confidence interval (CI): 15.8–38.0] for stratum 1 (n = 66) and 21.8% (95% CI: 14.2–31.1) for stratum 2 (n = 101). Patients with PD-L1–positive tumors (combined positive score ≥1) had numerically higher ORR than those with PD-L1–negative tumors, particularly in stratum 1 [stratum 1: 34.5% (95% CI: 17.9–54.3) vs 16.1% (95% CI: 5.5–33.7); stratum 2, 24.4% (95% CI: 12.9–39.5) vs 18.2% (95% CI: 8.2–32.7)]. Conclusions: Eribulin plus pembrolizumab was generally well tolerated and showed promising antitumor activity in mTNBC. Efficacy outcomes appeared influenced by line of therapy and PD-L1 status.

Background Patients with diabetes mellitus and coronary artery disease (CAD) represent a high-risk population, where comorbidities are common, and the progression of coronary heart disease is relatively rapid and extensive. The present survey, conducted nationwide in a Eurozone country, Greece, with a properly organized national health system, aimed to record specific data from a significant number of patients with diabetes and documented stable CAD (SCAD). Methods and Results We conducted our survey across the country, in private and public primary, secondary and tertiary care centers. A total of 1900 patients aged 71±10 years old suffering from both diabetes mellitus and chronic coronary syndromes were registered. Of the patients registered 574 (30.24%) were women. It was found that 506 (26.6%) of the 1900 surveyed patients showed typical angina symptoms, while another 560 (29.5%) patients had developed angina-equivalent symptoms according to their history. Additionally, 324 (17%) patients had atypical symptoms that could not easily be attributed to existing coronary artery disease and the remaining 510 (26.8%) of the 1900 patients did not exhibit any angina symptoms during their daily activities. Functional testing for myocardial ischemia was not performed in 833 patients (43.8%). Myocardial scintigraphy was the most commonly used noninvasive technique (644 patients, 34%), while 492 patients (25.9%) had an exercise test and 159 (8.4%) underwent stress echocardiography. Conclusion Real world data in this specific high-risk population of diabetic patients with SCAD offers the opportunity to identify and improve diagnostic and therapeutic practice in the health-care system of a European Union country.

IntroductionThere is consistent evidence that people with cerebral palsy (CP) do not engage in the recommended physical activity guidelines for the general population from a young age. Participation in moderate-to-vigorous physical activity is particularly reduced in people with CP who have a moderate-to-severe disability. RaceRunning is a growing disability sport that provides an opportunity for people with moderate-to-severe disability to participate in physical activity in the community. It allows those who are unable to walk independently to propel themselves using a RaceRunning bike, which has a breastplate for support but no pedals. The aim of this study is to examine the feasibility and acceptability of RaceRunning for young people with moderate-to-severe CP and the feasibility of conducting a definitive study of the effect of RaceRunning on cardiometabolic disease risk factors and functional mobility.Methods and analysisTwenty-five young people (age 5–21 years) with CP or acquired brain injury affecting coordination will be included in this single-arm intervention study. Participants will take part in one RaceRunning session each week for 24 weeks. Outcomes assessed at baseline, 12 and 24 weeks include body mass index, waist circumference, blood pressure, muscle strength, cardiorespiratory fitness, physical activity and sedentary behaviour, functional mobility, activity competence and psychosocial impact. Adverse events will be systematically recorded throughout the 24 weeks. Focus groups will be conducted with participants and/or parents to explore their views and experiences of taking part in RaceRunning.Ethics and disseminationApproval has been granted by Queen Margaret University Research Ethics Committee (REC) and the South East of Scotland REC. Results will be disseminated through peer-reviewed journals and distributed to people with CP and their families through RaceRunning and Athletic Clubs, National Health Service trusts and organisations for people with disabilities.Trial registration numberNCT04034342; pre-results.

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, remains the second leading cause of cancer-related death. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP-531. We report potent anti-tumor effects of unacylated ghrelin, dependent on cells being cultured in 3D in a biologically-relevant extracellular matrix. The mechanism of unacylated ghrelin-mediated growth inhibition involves activation of Gαi and suppression of MAPK signaling. AZP-531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

As a global actor, the European Union (EU) plays a leading role in international efforts to promote sustainable development globally. All sustainable objectives and targets need Information and Communication Technologies (ICTs) as key catalysts, since ICTs constitute tools of unprecedented power which help people to face the growing challenges of rising population, poverty, epidemics and climate change. Policy makers in the EU are increasingly putting ICTs into relations with sustainable regional development. This paper aims to study and assess the impact of ICT on the EU regional policy in terms of sustainable development by applying the multicriteria approach, PROMETHEE II, using the software Visual PROMETHEE. The criteria that were used in this research are the criteria that both the European Commission and member states define to assess the ICT implications of new EU legislation since 2010. The results revealed that the impact of ICT on EU sustainable regional policy has gotten stronger in the last two decades.

Background: The PI3K/Akt/mTOR pathway in part impacts tumorigenesis through modulation of host immune activity. To assess the effects of Akt inhibition on the tumor micro-environment (TME), we analyzed tumor tissue from patients with operable hormone receptor positive, HER2 negative breast cancer (BC) treated on a presurgical trial with the Akt inhibitor MK-2206.Methods: Quantitative multiplex immunofluorescence (qmIF) was performed using CD3, CD8, CD4, FOXP3, CD68, and pancytokeratin on biopsy and surgical specimens of MK-2206 and untreated, control patients. nanoString was performed on surgical specimens to assess mRNA expression from MK-2206-treated vs. control patients.Results: Increased CD3+CD8+ density was observed in post vs. pre-treatment tissue in the MK-2206-treated vs. control patients (87 vs. 0.2%, p < 0.05). MK-2206 was associated with greater expression of interferon signaling genes (e.g., IFI6, p < 0.05) and lower expression of myeloid genes (CD163, p < 0.05) on differential expression and gene set enrichment analyses. Greater expression of pro-apoptotic genes (e.g., BAD) were associated with MK-2206 treatment (p < 0.05).Conclusion: Akt inhibition in operable BC was associated with a favorable immune profile in the TME, including increased CD3+CD8+ density and greater expression of interferon genes. Additional studies are warranted, as this may provide rationale for combining Akt inhibition with immunotherapy.

BackgroundThe available evidence on whether neuraminidase inhibitors reduce mortality in patients with influenza is inconclusive and focuses solely on influenza A/H1N1pdm09. We assessed whether early oseltamivir treatment (≤48 hours from symptom onset) decreases mortality compared to late treatment in a large cohort of critically ill patients with influenza of all types.MethodsThe study included all adults with laboratory-confirmed influenza hospitalized in intensive care units (ICUs) in Greece over 8 seasons (2010–2011 to 2017–2018) and treated with oseltamivir. The association of early oseltamivir with mortality was assessed with log-binomial models and a competing risks analysis estimating cause-specific and subdistribution hazards for death and discharge. Effect estimates were stratified by influenza type and adjusted for multiple covariates.ResultsA total of 1330 patients were studied, of whom 622 (46.8%) died in the ICU. Among patients with influenza A/H3N2, early treatment was associated with significantly lower mortality (relative risk, 0.69 [95% credible interval {CrI}, .49–.94]; subdistribution hazard ratio, 0.58 [95% CrI, .37–.88]). This effect was purely due to an increased cause-specific hazard for discharge, whereas the cause-specific hazard for death was not increased. Among survivors, the median length of ICU stay was shorter with early treatment by 1.8 days (95% CrI, .5–3.5 days). No effect on mortality was observed for A/H1N1 and influenza B patients.ConclusionsSeverely ill patients with suspected influenza should be promptly treated with oseltamivir, particularly when A/H3N2 is circulating. The efficacy of oseltamivir should not be assumed to be equal against all types of influenza.

For primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), higher pretreatment tumor-infiltrating lymphocytes (TILs) correlates with increased pathologic complete response (pCR) rates, and improved survival. We evaluated the added prognostic value of residual disease (RD) TILs to residual cancer burden (RCB) in predicting survival post-NAC.We combined four TNBC NAC patient cohorts who did not achieve pCR. RD TILs were investigated for associations with recurrence-free survival (RFS), and overall survival (OS) using Cox models with stromal TILs as a continuous variable (per 10% increment). The likelihood ratio test was used to evaluate added prognostic value of RD TILs.A total of 375 RD TNBC samples were evaluable for TILs and RCB. The median age was 50 years, with 62% receiving anthracycline/taxane chemotherapy. The RCB class after NAC was 11%, 50%, and 39% for I, II, and III, respectively. The median RD TIL level was 20% (IQR 10-40). There was a positive correlation between RD TIL levels and CD8+ T-cell density (ρ = 0.41). TIL levels were significantly lower with increasing post-NAC tumor (P = 0.005), nodal stage (P = 0.032), but did not differ by RCB class (P = 0.84). Higher RD TILs were significantly associated with improved RFS (HR: 0.86; 95% CI 0.79-0.92; P 0.001), and improved OS (HR: 0.87; 95% CI 0.80-0.94; P 0.001), and remained significant predictors in multivariate analysis (RFS P = 0.032; OS P = 0.038 for OS). RD TILs added significant prognostic value to multivariate models including RCB class (P 0.001 for RFS; P = 0.021 for OS). The positive prognostic effect of RD TILs significantly differed by RCB class for RFS (PInt=0.003) and OS (PInt=0.008) with a greater magnitude of positive effect observed for RCB class II than class III.TIL levels in TNBC RD are significantly associated with improved RFS and OS and add further prognostic information to RCB class, particularly in RCB class II.

The circular economy refers to a development strategy that allows economic growth by optimising the use of natural resources, minimising environmental pressures, transforming supply chains and consumption patterns and redesigning production systems so that they are restorative or regenerative by intention and design. A transition to a more circular economy requires a systemic approach that considers the interconnections that exist within and between sectors, institutions and local actors. The aim of the paper is to reflect on the characteristics of a territorial model for a circular rural economy, which directs its actions through a local lens to promote closer interaction between actors, by optimising the use of resources, and between production processes and social and cultural matrices.

Summarization: Environmental sustainability has become a major goal of public policies throughout the world, as environmental resources are continually eliminated. Climate change mitigation involves decarbonizing electricity generation as the most important energy system-wide change, with a vital role for energy efficiency. The utilization and development of Renewable Energy Sources (RES) constitutes the most critical measure to safeguard energy security, strengthen environmental protection, and tackle climate change. RES are favored as a means of reducing the use of fossil fuels. The market of RES is continuously developing and promoted through the Internet. Renewable energy is, by definition, sustainable and clean. Moreover, the market of RES offers the opportunity to tackle the increasing depletion of fossil resources and the associated environmental impacts. The paper aims to present RES and study the energy policy in EU and Greece. Furthermore, the status of the renewable energy market in Greece and especially in the Prefecture of Thessaloniki is presented. The Internet research retrieved 30 enterprises that promote renewable energy in the Prefecture of Thessaloniki, which were analyzed according to 18 characteristics representing internet adoption. The multicriteria method used for total ranking is PROMETHEE II. According to PROMETHEE II findings, the ‘superior’ websites can be used to form a conceptual content model while designing an enhanced website for a RES enterprise. The results show that these enterprises in the Prefecture of Thessaloniki must adjust to the new ‘information era’ and aim to become more effective and efficient while creating their autonomous website. Furthermore, most enterprises with their own websites in this sector are generally still in the initial adoption phase and they should further mature in the next phases of e-commerce adoption. Presented on: Technological Forecasting and Social Change

Background Foot drop in people with multiple sclerosis (pwMS) often managed with assistive technologies, such as functional electrical stimulation and ankle foot orthoses. No evidence synthesis exists for the psychometric properties of outcomes used to evaluate the efficacy of these interventions. Objective This systematic review aimed to identify the outcome measures reported to assess the benefits of assistive technology for pwMS and then synthesize the psychometric evidence in pwMS for a subset of these measures. Methods Two searches in eight databases were conducted up to May 2017. Methodological quality was rated using the COSMIN guidelines. Overall level of evidence was scored according to the Cochrane criteria. Results The first search identified 27 measures, with the 10 m walk test, gait kinematics and Physiological Cost Index (PCI) most frequently used. The second search resulted in 41 studies evaluating 10 measures related to walking performance. Strong levels of evidence were found for the internal consistency and test-retest reliability of the Multiple Sclerosis Walking Scale-12 and for the construct validity for Timed 25 Foot Walk. No psychometric studies were identified for gait kinematics and PCI in pwMS. There was a lack of evidence for measurement error and responsiveness. Conclusion Although a strong level of evidence exists for some measures included in this review, there was an absence of psychometric studies on commonly used measures such as gait kinematics. Future psychometric studies should evaluate a wider range of walking related measures used to assess the efficacy of interventions to treat foot drop in pwMS.

Background: Tumor infiltrating lymphocytes (TILs) evaluated in the primary tumor biopsy or surgical resection have been well established as having prognostic significance in patients with triple negative breast cancer (TNBC) and HER2+ breast cancer treated with adjuvant chemotherapy (Savas et. al, Nat Rev Clin Oncol 2016). In TNBC, stromal TILs behave as a continuous variable with every 10% increase in TIL resulting in a decrease in risk of recurrence and death. The definition of lymphocyte-predominant breast cancer (LPBC) has been used for tumors that contain 50%–60% TILs and usually have a particularly good outcome (Salgado et al, Ann Oncol 2015). Our group recently demonstrated in a phase II single arm study that tetrathimolybdate (TM), a copper-depleting agent, resulted in improved event free survival (EFS) for TNBC patients compared to historical controls. The 2-year event-free survival (EFS) for stage 2-3 and stage 4 NED was 91% and 67%, respectively. In this analysis, our goal was to explore whether the encouraging results we observed were influenced by enrolling TNBC patients with better prognostic factors at initial diagnosis, namely higher stromal TIL score, in our copper depletion trial. Methods: Archived primary breast tissue was available from 67 of the 75 patients enrolled in the phase II TM trial. The phase II study included patients with stage II TNBC or stage III or IV NED breast cancer patients, who were treated with TM for 2 years or until relapse. Here we focused on the 30 patients with TNBC. The demographic data for the patients is included in the following table. Patient DemographicsAge at diagnosisStage at study entryPrior Adjuvant or Neoadjuvant therapyNumber of prior chemotherapy regimens in metastatic setting%Tumor Infiltrating Lymphocytes504Adjuvant110543AAdjuvantn/a30563AAdjuvantn/a20513CNeoadjuvantn/a The number of TILs in each sample was calculated by an experienced pathologist using published criteria (Salgado et al, Ann Oncol 2015). We used TILs >50% to define LPBC. Results: Overall, we found that only 3/30 (10%) of TNBC patients had TILs >50%. In addition, 14/30 (46.7%) of TNBC patients had tumors with 10% v. Conclusions: Only 10% of TNBC patients enrolled in the study had LPBC at diagnosis thus indicating that this cohort was not enriched for patients with immunogenic tumors. When stratified by TILs >10% or Citation Format: Rybstein MD, Nackos E, Kornhauser N, Cigler T, Andreopoulou E, Moore A, Cobham M, Fitzpatrick V, Demaria S, Vahdat LT. Tumor infiltrating lymphocytes (TILS) among high risk for recurrence breast cancer patients treated with tetrathimolybdate (TM) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-10.

Background: Metals have emerged as a viable therapeutic target for a new generation of anti-cancer and anti-metastatic agents. Copper, an essential trace element, serves as an important catalytic cofactor in several biological functions and has emerged as an essential factor in carcinogenesis. Among other elements, bone marrow derived VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent lysyl oxidase (LOX) are key elements in tumor progression. We hypothesized tetrathiomolybdate (TM)-associated copper depletion (CD) inhibits tumor metastases by reducing the number of EPCs and other copper dependent processes in the pre-metastatic niche. These results are an update of our previously reported study (Chan N, Willis A, Kornhauser N et al. Influencing the Tumor Microenvironment: Phase 2 Study of Copper Depletion with Tetrathiomolybdate in High Risk Breast Cancer and Preclinical Models of Lung Metastases. Clin Cancer Res. October 21, 2016) with longer follow-up. Methods: A single arm phase II study of breast cancer (BC) patients (pts) at high risk for recurrence, defined as node+ triple negative (TNBC), stage 3 and 4 with no evidence of disease (NED) were enrolled on a trial of CD with TM. TM was given to maintain ceruloplasmin (Cp) levels between 8-16 mg/dl for two years with an extension phase or until relapse. The primary endpoint was a change in EPCs measured by flow cytometry before and during treatment. Secondary endpoints included tolerability, safety, PFS and LOXL-2 levels. Results: Seventy-five pts received 2778 cycles of TM on the primary and extension study. The primary study treatment duration was 24 cycles (each cycle is 28 days) plus an extension phase. The median age is 51 years (range 29-66). Forty-five pts have stage 2/3 BC and 30 with stage 4 NED. Forty-eight percent of pts are TNBC and 40% of pts are stage 4 NED. Median Cp levels were monitored with each cycle. A decrease from 28 to 16 (p Conclusions: TM is safe, well tolerated and appears to affect multiple components of the tumor microenvironment that have been identified in pre-clinical models as important for progression. Ongoing studies in banked specimens are underway to further delineate its effect on copper dependent processes necessary for metastases. Randomized trials are warranted, especially in patients who are at high risk for relapse such as those with TNBC. Citation Format: Sahota S, Willis A, Kornhauser N, Ward M, Cobham M, Cigler T, Moore A, Andreopoulou E, Fitzpatrick V, Schneider S, Prima N, Wiener A, Ko D, De Laurentiis A, Warren JD, Rubinchik A, Mittal V, Vahdat LT. A phase II study of copper-depletion using tetrathiomolybdate in patients with breast cancer at high risk for recurrence: Updated results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-02.

Background Poly-ADP-ribose-polymerase is an essential nuclear enzyme, involved in base-excision repair of damaged DNA. Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy. Methods The primary objective of this phase I trial was to determine the safety and identify the recommended phase II dose of the combination of low-dose oral C (50, 75, 100, and 125 mg) once daily in combination with veliparib (V) (100, 200, and 300 mg) administered twice a day (BID) for 21-day cycles using a standard 3 + 3 design in patients with metastatic human epidermal growth factor receptor 2/neu-negative breast cancer. Dose-limiting toxicity was defined as any grade 3 non-hematologic toxicity or grade 4 thrombocytopenia/neutropenia occurring during cycle 1. Results A total of 31 patients were enrolled; 19 were treated with 50 mg of C and 12 were treated at higher doses (75, 100, or 125 mg), with V doses ranging from 50 to 300 mg BID. The recommended phase II dose of the combination was V 200 mg orally BID plus C 125 mg orally daily, with nausea and headache dose-limiting at higher V dose levels. Objective response or stable disease for at least 24 weeks occurred in 3 (43%) of 7 patients with known deleterious germline BRCA mutations and 2 (11%) of 19 patients with negative/unknown mutation status (P = .1). Conclusion The combination of oral continuous dosing of V (200 mg orally BID) with metronomic C (50, 75, 100, and 125 mg daily) is well-tolerated and shows antitumor activity in patients with BRCA–mutation-associated metastatic human epidermal growth factor receptor 2/neu-negative breast cancer.

Sustainable development represents a crucial environmental policy framework in order to provide multiple benefits for climate, biodiversity and people. The National Forest Parks (NFP) represent protected areas with important forest diversity that play a critical role, both in reversing biodiversity loss and contributing to socio-economic development. The European Structural and Investment Funds (ESIF) pursue the preservation and improvement of the environment in the context of sustainable development. To date in Greece, 16 operational projects have been approved through two ESIFs and concern six NFPs which are supervised by Management Bodies. Critical Assessment of the projects and SWOT analysis for the six Management Bodies has also been implemented. These results highlight the existence of common sustainability goals, which focus on the protection of Natura 2000 sites and on preserving biodiversity, to financial support the NFPs with vehicles and IT equipment, rather than promote sustainability.

"Internet of Things" (IoT), e la vasta rete di dispositivi che comunicano su Internet senza il coinvolgimento umano. Tuttavia, l’economia circolare predomina nei recenti sforzi di ricerca verso la sostenibilita. La questione alimentare e predominante in 10 su 17 degli obiettivi di sviluppo sostenibile di recente istituzione. Grazie all’ottimizzazione della catena di fornitura e alle linee di distribuzione piu brevi, sara possibile risolvere problemi nell’ambito dell’economia circolare nell’aspetto alimentare quali: riduzione degli sprechi alimentari, miglioramento della tracciabilita degli alimenti, miglioramento della qualita degli alimenti, acquisizione dell’autenticazione alimentare, ottimizzazione della catena di approvvigionamento e logistica, ecc.

Poly(ADP-ribose) polymerase inhibitors are FDA-approved for treatment of BRCA mutated metastatic breast cancer (MBC). Prior studies demonstrated benefit of adding oral PARPi veliparib to carboplatin and paclitaxel in BRCA mutation positive patients with MBC. We sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple negative (TNBC) or hormone receptor (HR) positive, HER2-negative with defective functional Fanconi Anemia (FA) DNA-repair pathway. Patients received escalating doses of veliparib on a 7, 14, or 21-day schedule with carboplatin every 3 weeks. Patients underwent [18]fluoro-3’-deoxythymidine (18FLT) positron emission tomography (PET) imaging, assessed in a blinded fashion. Forty-four patients (39 TNBC, 5 HR-positive/HER2-negative with a defective FA pathway) received a median of 5 cycles (range 1-36). Observed DLTs were grade (G) 4 thrombocytopenia (N=4), G4 neutropenia (N=1) and G3 akathisia (N=1). Common grade 3-4 toxicities included thrombocytopenia, lymphopenia, neutropenia, anemia, and fatigue. Of 43 patients evaluable for response, 18.6% achieved partial response and 48.8% had stable disease. Median progression free survival was 18.3 weeks. RP2D of veliparib was established at 250 mg twice daily on days 1-21 along with carboplatin at AUC 5. Patients with partial response had significant drop in SUVmax of target lesions between baseline and early 18FLT-PET (day 7-21; ptrend=0.006). Continuous dosing of veliparib and every three week carboplatin demonstrated activity and acceptable toxicity. Decrease in SUVmax on 18FLT-PET scan during the first cycle of this therapy can identify patients likely to have a response.IMPLICATIONS FOR PRACTICEThe BROCADE studies suggest that patients with BRCA mutation benefit from addition of PARP inhibitor veliparib to carboplatin plus paclitaxel. In this study, we demonstrate that a higher dose of veliparib is tolerable and active in combination with carboplatin alone. With growing interest in imaging-based early response assessment, we demonstrate that decrease in 18FLT-PET SUVmax in the first cycle of therapy is significantly associated with response. Collectively, this study provides clarity on dosing of veliparib with carboplatin in advanced breast cancer while providing additional data on the potential for novel PET imaging modalities in monitoring therapy response.

Breast cancer is the most common type of cancer in women and notwithstanding important therapeutic advances, it remains the second leading cause of cancer-related death in the US. Despite extensive research relating to the hormone ghrelin, responsible for the stimulation of growth hormone release and appetite, little is known of the effects of its unacylated form, especially in cancer. One major area of research relates to its reported effects to increase insulin sensitivity in diabetics, this being the basis for the development of unacylated ghrelin analog, AZP531 or livoletide, now in clinical trials for the treatment of Prader-Willi Syndrome. The mechanism of action of unacylated ghrelin is largely uncharacterized, in any system, because it does not bind to or activate the cognate ghrelin receptor, GHSR1a. The present study aimed to characterize effects of unacylated ghrelin on breast cancer cells, define its mechanism of action, and explore the therapeutic potential of unacylated ghrelin or analog AZP531. We report potent effects of unacylated ghrelin, at picomolar doses, on the growth of breast cancer cells, dependent on 3D culture and activation of Gαi. Suppression of MAPK signaling by unacylated ghrelin leads to cell cycle arrest and apoptosis. AZP531 also suppresses the growth of breast cancer cells in vitro and in xenografts, and may be a novel approach for the safe and effective treatment of breast cancer.

Background Poly(ADP‐ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA‐mutated metastatic breast cancer. Furthermore, the BROCADE studies demonstrated benefit of adding an oral PARPi, veliparib, to carboplatin and paclitaxel in patients with metastatic breast cancer harboring BRCA mutation. Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple‐negative (TNBC) or hormone receptor (HR)‐positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA‐repair pathway based on FA triple staining immunofluorescence assay. Materials and Methods Patients received escalating doses of veliparib on a 7‐, 14‐, or 21‐day schedule with carboplatin every 3 weeks. Patients underwent [18]fluoro‐3′‐deoxythymidine (18FLT) positron emission tomography (PET) imaging. Results Forty‐four patients (39 TNBC, 5 HR positive/HER2 negative with a defective FA pathway) received a median of 5 cycles (range 1–36). Observed dose‐limiting toxicities were grade (G) 4 thrombocytopenia (n = 4), G4 neutropenia (n = 1), and G3 akathisia (n = 1). Common grade 3–4 toxicities included thrombocytopenia, lymphopenia, neutropenia, anemia, and fatigue. Of the 43 patients evaluable for response, 18.6% achieved partial response and 48.8% had stable disease. Median progression‐free survival was 18.3 weeks. RP2D of veliparib was established at 250 mg twice daily on days 1–21 along with carboplatin at area under the curve 5. Patients with partial response had a significant drop in maximum standard uptake value (SUVmax) of target lesions between baseline and early in cycle 1 based on 18FLT‐PET (day 7–21; p trend = .006). Conclusion The combination of continuous dosing of veliparib and every‐3‐week carboplatin demonstrated activity and an acceptable toxicity profile. Decrease in SUVmax on 18FLT‐PET scan during the first cycle of this therapy can identify patients who are likely to have a response. Implications for Practice The BROCADE studies suggest that breast cancer patients with BRCA mutation benefit from addition of veliparib to carboplatin plus paclitaxel. This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone. With growing interest in imaging‐based early response assessment, the authors demonstrate that decrease in [18]fluoro‐3′‐deoxythymidine positron emission tomography (FLT‐PET) SUVmax during cycle 1 of therapy is associated with response. Collectively, this study established a safety profile of veliparib and carboplatin in advanced breast cancer while also providing additional data on the potential for FLT‐PET imaging modality in monitoring therapy response., This phase I study of veliparib in combination with carboplatin in patients with metastatic triple negative or hormone receptor positive, HER2‐negative breast cancer with somatic deficiency in the Fanconi anemia pathway, established a safety profile and recommended phase II dose of the combination and provided new information on the use of novel PET imaging modalities in monitoring therapy response.

PURPOSE We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis. PATIENTS AND METHODS Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated. RESULTS Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant. CONCLUSION Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

Objectives Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent. Methods We used nine seasons of comprehensive nationwide surveillance data from Greece (2010–2011 to 2018–2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. Results For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38–2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54–4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons (≥65 vs. 40–64 years, RR for intensive care 5.42, 95% CI 3.45–8.65, and RR for death 6.19, 95%CI 4.05–9.38). Within the 40–64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B. Discussion Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.

The Information and Communication Technology (ICT) sector provides a wide range of services for different actors according to their type of actions. In fact, adoption of ICT-enhanced policies is one of the top agendas for governments today in most developing countries. The European Union (EU) and its Member States have a long tradition in development cooperation. The objective of this research is to study the contribution of ICT in the development policy in EU and present the current status by ranking these policies. EU development policies are evaluated qualitatively according to their ICT dependence and complexity levels. The questions, used as criteria, have been retrieved from the official “ICT Implication Assessment method of EU Legislation.” Following the multicriteria method of PROMETHEE II is applied for the total ranking in order to identify the “superior” ones, which present high dependence on and complexity of the ICT implications.

The aim of the paper is to evaluate Forest Policy performance in the countries of Europe, using a multiple criteria analysis based on forestry sector data retrieved by Eurostat. Multiple Criteria Decision Analysis is strongly connected with Policy and decision-making, and it can mitigate the uncertainty of planning providing robust solutions, while it is broadly used for agri-environmental issues. The PROMETHEE method was used to provide a ranking of the European countries in their Forest Policy performance drawing on data covering all three sustainability pillars: economy, environment, and society. According to the findings, the Czech Republic has the best performance among the examined countries regarding Forest Policy implementation. Other countries that can be singled out for best practices are Germany, Slovakia, and Hungary. Greece, on the other hand, is ranked last and the evidence verifies that the economic crisis has seriously affected the country in multiple areas. The country rankings were more volatile in the middle places, while countries with high or low performance on Forest Policy implementation maintained a more stable position across the three scenarios. The forest area as an input significantly affects the final ranking of the European countries. In general, large areas available for wood supply lead to a lower country ranking in Forest Policy performance as in Sweden, Finland, and Spain; only Germany achieves a high ranking among countries with large areas available for wood supply. The findings provide an overview of the current situation relating to Forest Policy implementation among European countries and could be used by the European Union in a future framework of Common Forest Policy in the EU.

Background Many people with multiple sclerosis (pwMS) experience walking impairments often including foot drop, evident as either reduced dorsiflexion at initial contact and/or at the swing phase of the gait cycle. To measure even subtle differences in ankle kinematics, 3D gait analysis is considered a ‘gold’ standard. However, the psychometric properties of ankle kinematics in the MS population have not yet been examined. Objective The aim of the study was to examine test-retest relative and absolute reliability of sagittal ankle kinematics and spatiotemporal parameters in two groups of pwMS with different levels of walking impairment. Methods Two groups of pwMS underwent 3D gait analysis on two occasions 7–14 days apart. Group A consisted of 21 (14 female) people with Expanded Disability Status Scale (EDSS) 1–3.5 and group B consisted of 28 participants (14 female) with EDSS 4-6. The Intraclass Correlation Coefficient (ICC2,2), standard error of measurement (SEM) and minimal detectable change (MDC95%) were calculated for peak dorsiflexion (DF) in swing, ankle angle at initial contact (IC), gait profile score (GPS), walking speed, cadence and step length. Results Both groups presented ‘excellent’ ICC values (>0.75) for DF in swing, IC and step length of most and least affected limbs, walking speed and cadence, with GPS for both limbs exhibiting ‘fair’ to ‘good’ ICCs (0.489–0.698). The MDC95% values for all ankle kinematic parameters in group A were lower (1.9°–4.2°) than those in group B (2.2°–7.7°). Conclusion The present results suggest that ankle kinematic and spatiotemporal parameters derived from 3D gait analysis are reliable outcome measures to be used in the MS population. Further, this study provides indices of reliability that can be applied to both clinical decision making and in the design of studies aimed at treating foot drop in people with MS.

In the present investigation, a binary strategy for the development of wavelength-selective semi-transparent dye-sensitized solar cells (DSSCs), with a proper transmittance in the region of photosynthetic active radiation, for greenhouses-oriented applications is examined. Two new low-cost triphenylamine-based dyes and a highly transparent iodine-free electrolyte are proposed as alternatives to the conventional expensive ruthenium-based dyes and yellowship iodine-based electrolytes for attaining more suitable optical characteristics to DSSCs that are intended to be used as cladding materials in greenhouses. The spectral engineered DSSCs demonstrated a quite high external quantum efficiency (almost 85%) in the whole blue and green part of the visible spectrum, while providing high transparency (up to 55%) in the red part, which is of the most important ones for the process of photosynthesis. The present work demonstrates that the development of solar cells with an energy conversion efficiency on the order of 6% combined with a crop growth factor of almost 35% is feasible. To the best of the authors’ knowledge, these combined performance parameters are of the best-reported ones for “agrivoltaics”, giving new insights for developing energy-autonomous greenhouses, further suggesting that spectral engineering is an effective strategy to improve the performance of DSSCs for niche applications.

BACKGROUND: PARP, an essential nuclear enzyme, is involved in the recognition of DNA damage and facilitation of DNA base-excision repair (BER). PARP inhibition sensitizes tumor cells to cytotoxic agents which induce DNA damage, including C. Metronomic dosing of C may optimize potential for synergy with PARP inhibitors, and also inhibits angiogenesis (Kerbel et al, Nat Rev Cancer, 4:423-36, 2004) and may enhance anti-tumor immunity (Ghiringhelli et al. Cancer Immunol Immunother 56:641–648, 2007) V is an oral small molecule inhibitor of PARP which potentiates the antineoplastic activity of DNA damaging agents such as C in MX-1 breast xenograft model (Donawho et al Clin Cancer Res 13:2728-37, 2007). We performed a phase I trial of metronomic dose oral C plus V in patients with MBC. METHODS: The primary objective was to determine the safety and identify the recommended phase II dose (RPTD) of the combination of low-dose oral C once daily in combination with V (100, 200, 300 mg) administered BID for 21 days using a standard 3+3 design. Eligibility included HER2/neu negative MBC, ECOG PS 0-1, and at least 1 prior chemotherapy regimen for MBC. Dose limiting toxicity (DLT) was defined as any Grade 3 non-hematological toxicity or Grade 4 thrombocytopenia/neutropenia occurring during cycle 1. After the RPTD of V was shown to be 200 mg BID with C 50 mg daily, the trial was amended to increase the C dose to 75, 100 and then 125 mg daily until hematologic toxicity was dose-limiting. RESULTS: 31 patients were enrolled, 19 treated with 50 mg of C and 12 treated at higher doses (75-125 mg), with V doses ranging from 50 mg-300 mg BID (see table);5 patients with not evaluable due to rapid disease progression (N=2), non-compliance (N=2), or tumor pain that was not a DLT (N=1). Median age was 52 years (28-72 years), 14 (45 %) had triple negative disease, all had at least 1 prior chemotherapy regimen for metastasis (median 2, range 1-8), and, 7 had germline BRCA mutations, (3 BRCA1 and 4 BRCA2). When combined with 50 mg C daily, RPTD of V was 200 mg PO BID, with nausea being DLT at 300 mg BID. DLT was not observed in any of the 9 additional patients. The median number of cycles given was 3 (range 1-14). Clinical benefit (response or stable disease for at least 24 weeks) occurred in 3/7 (43%), 1/3 (33%) and 1/16(6%) for BRCA mutated, BRCA negative and BRCA unknown, respectively. Median progression-free survival was 4.3 months (1.2-10.9 months) for BRCA mutated patients and 2 months (0.7-10 months) for non-mutated. CONCLUSIONS: The combination of oral continuous dosing of V (200 mg PO BID) with metronomic C (50, 75, 100 and 125 mg daily) is well tolerated and shows antitumor activity in patients with BRCA mutation associated MBC. The RPTD is C 125 mg daily plus V 200 mg BID, although further escalation of the C dose may be feasible since DLT was not seen at this dose level. Dose LevelsDose Level# Patients/Evaluable# DLTType of DLTDL 1 :V 50mg , C 50mg3/30 DL 2 :V 100 mg, C 50mg4/30 DL 3 :V 200 mg, C 50mg6/61HeadacheDL 4 :V 300 mg, C 50mg6/52Nausea (N=2)DL 3A :V 200 mg; C 75mg3/30 DL 3B :V 200 mg, C 100mg6/30 DL 3C :V 200 mg, C 125mg3/30 Citation Format: Anampa JD, Patel M, Pellegrino C, Fehn K, Makower D, Oh S-y, Noah K, Chen A, Sparano JA, Andreopoulou E. Phase I study of low dose oral cyclophosphamide (C) plus the poly-ADP-ribose- polymerase (PARP) inhibitor veliparib (V) in women with HER2/neu-negative inoperable locally advanced/metastatic breast cancer (MBC): NCI P8853 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-12-08.

The role of bone-targeted agents in the adjuvant treatment of early breast cancer has been debated for decades. A recent meta-analysis of individual patient data from 18,766 women provides compelling evidence supporting the use of these agents in postmenopausal women with early-stage breast cancer. Postmenopausal women who received a bisphosphonate had a significant reduction in breast cancer mortality (14.7 vs 18%; p = 0.002) and in overall survival (21.1 vs 23.5%; p = 0.005). Some questions remain such as; what bone-targeted agent is the best? What are the optimum doses, durations and schedules? Which patients benefit the most? The decision to include a bone-targeted agent should consider the absolute risk of distant recurrence and breast cancer mortality.

Triple-negative breast cancer (TNBC) is a molecularly diverse grouping with poor prognosis for which chemotherapy remains the foundation of treatment. The molecular heterogeneity of the disease rationalizes its diverse biological behavior and differential response to treatment. Estimates of up to 20% of patients diagnosed have germline mutations in DNA-damage repair-pathway genes, namely BRCA1 and 2, and this can be used to select patients likely to respond to platinums and/or inhibitors of poly(ADP-ribose) polymerase (PARP). Similar strategies can be utilized in other subtypes of TNBC that have ‘BRCA-like' tumor biology due to the presence of mutations in alternate DNA-damage repair genes. The diverse biological behavior of TNBC and its variable response to chemotherapy were largely decoded following genotyping studies that enabled the identification of distinct molecular subtypes, such that the biological and genetic heterogeneity of the disease could be understood. This subsequently enabled the identification of therapeutic ‘vulnerabilities' for each subtype that encompass biological processes including proliferation, DNA repair, apoptosis, angiogenesis, immune modulation, and invasion and metastasis. To expedite the development of therapies for high-risk, early-stage breast cancer, we have adopted novel trial designs and re-defined endpoints as surrogates of clinical outcomes. The purpose of this review is to highlight the current standard and experimental treatment options for TNBC.

Regional sustainability promotes an integrated approach to planning and development in regional communities. European Union legislative acts bring together all levels of government to achieve a holistic approach to sustainability using Information and Communication Technologies tools for better delivery of services. Today, there has been observed an increasing interest in applying e-government to different business sectors such as the environmental sector. Sustainable management of National Forest Parks relies on a complete understanding of the goods and services, which are provided to the society. This paper aims to study e-government websites concerning the 10 Greek National Forest Parks and analyse the websites as to their qualitative and quantitative features. Then, the electronic services model adoption of the websites is assessed. The e-government websites are classified in electronic services adoption stages starting from a simple presence of the government agency in the Internet to the total electronic services integration through multiple ICT tools and applications provision according to content features accomplished by the websites. The findings can be helpful for managers, policy makers, web designers, environmentalists and government agencies.

In this work, the fabrication and characterization of flexible organic light emitting diode (OLED) devices by printing processes is presented. New synthesized anthracene-based polymer as well as commercially available polymers such as polyfluorenes and polyphenylene vinylenes were applied as emitting materials. The photoluminescence (PL) properties of the polymer films were evaluated revealing the characteristic emission of each material. The optical properties of the polymers were investigated by NIR-Vis-far UV spectroscopic ellipsometry. The accurate determination of the thickness and the optical properties were derived. Furthermore, electro-optical characteristics brightness, chromaticity, and current density–voltage characteristics of the devices were obtained. Correlations between the optical properties, PL characteristics, and device performances were established. This provides substantial insights into the final design of the optimum final multi-layer structure of the OLEDs whereas the potentiality for the development of flexible OLEDs with bigger active area devices by printing processes is demonstrated.