Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Disaster Resilience Education and Research Roadmap for Europe 2030 : ANDROID Report

A disaster resilience education and research roadmap for Europe 2030 has been launched. This roadmap represents an important output of the ANDROID disaster resilience network, bringing together existing literature in the field, as well as the results of various analysis and study projects undertaken by project partners.The roadmap sets out five key challenges and opportunities in moving from 2015 to 2030 and aimed at addressing the challenges of the recently announced Sendai Framework for Disaster Risk Reduction 2015-2030. This roadmap was developed as part of the ANDROID Disaster Resilience Network, led by Professor Richard Haigh of the Global Disaster Resilience Centre (www.hud.ac.uk/gdrc ) at the School of Art, Design and Architecture at the University of Huddersfield, UK. The ANDROID consortium of applied, human, social and natural scientists, supported by international organisations and a stakeholder board, worked together to map the field in disaster resilience education, pool their results and findings, develop interdisciplinary explanations, develop capacity, move forward innovative education agendas, discuss methods, and inform policy development. Further information on ANDROID Disaster Resilience network is available at: http://www.disaster-resilience.netAn ANDROID Disaster Resilience Network ReportANDROI

ENCOURAGING ATTRIBUTES IN URBAN RECREATIONAL WALKAWAYS: USER PERSPECTIVES

Numerous health concerns such as obesity is increasingly prevalent among many urban dwellers followed by lack of physical exercise even walking. Limited space in urban settings to provide adequate open spaces, providing recreational facilities is a key issue experienced in urban areas in Sri Lanka. Thus, an ideal solution arises as 'walking paths,' where only a strip of land is required. Among the limited studies directly rely on the attributes in walking paths, there are studies on ‘adults walking in open spaces’ discussing some attributes should consider in developing the facility. However, no evidence to date on the attractive attributes or the adequacy of the attributes in the walking paths. Accordingly. the main aim of this study is to examine the public perception on attributes of walking avenues in urban areas of Sri Lanka. Data collected through a self-administered questionnaire on ten attributes from a convenience sample of 150 users selected from three separate settings. The descriptive statistics, univariate analysis, hoc multiple comparisons, and homogeneous subsets technique were used in the analysis. Results reveals, safety as the preferred attribute while shading and natural settings also significant. An income variation presents that the respondents with above the income level of LKR 65,000 preferred cafeterias providing herbal drinks while the users with below that income level are less interest with the attributes of changing rooms and street vendors. It is recommended to consider the preferred attributes in developing future walking paths to encourage the public to get the full benefits. Keywords: Attractive Attributes, Public Perception, Urban Setting, Walkaways, Sri Lanka

The Double Pulsar Eclipses I: Phenomenology and Multi-frequency Analysis

The double pulsar PSR J0737-3039A/B displays short, 30 s eclipses that arise around conjunction when the radio waves emitted by pulsar A are absorbed as they propagate through the magnetosphere of its companion pulsar B. These eclipses offer a unique opportunity to probe directly the magnetospheric structure and the plasma properties of pulsar B. We have performed a comprehensive analysis of the eclipse phenomenology using multi-frequency radio observations obtained with the Green Bank Telescope. We have characterized the periodic flux modulations previously discovered at 820 MHz by McLaughlin et al., and investigated the radio frequency dependence of the duration and depth of the eclipses. Based on their weak radio frequency evolution, we conclude that the plasma in pulsar B's magnetosphere requires a large multiplicity factor (~ 10^5). We also found that, as expected, flux modulations are present at all radio frequencies in which eclipses can be detected. Their complex behavior is consistent with the confinement of the absorbing plasma in the dipolar magnetic field of pulsar B as suggested by Lyutikov & Thompson and such a geometric connection explains that the observed periodicity is harmonically related to pulsar B's spin frequency. We observe that the eclipses require a sharp transition region beyond which the plasma density drops off abruptly. Such a region defines a plasmasphere which would be well inside the magnetospheric boundary of an undisturbed pulsar. It is also two times smaller than the expected standoff radius calculated using the balance of the wind pressure from pulsar A and the nominally estimated magnetic pressure of pulsar B.Comment: 9 pages, 7 figures, 3 tables, ApJ in pres

Heterogeneous Diffusion in Highly Supercooled Liquids

The diffusivity of tagged particles is demonstrated to be very heterogeneous on time scales comparable to or shorter than the $\alpha$ relaxation time $\tau_{\alpha}$ ($\cong$ the stress relaxation time) in a highly supercooled liquid via 3D molecular dynamics simulation. The particle motions in the relatively active regions dominantly contribute to the mean square displacement, giving rise to a diffusion constant systematically larger than the Einstein-Stokes value. The van Hove self-correlation function $G_s(r,t)$ is shown to have a long distance tail which can be scaled in terms of $r/t^{1/2}$ for t \ls 3\tau_{\alpha}. Its presence indicates heterogeneous diffusion in the active regions. However, the diffusion process eventually becomes homogeneous on time scales longer than the life time of the heterogeneity structure ($\sim 3 \tau_{\alpha}$).Comment: 4 pages, 5 figure

ROLE OF MICROFINANCE IN EMPOWERING POOR RURAL HOUSEHOLDS: A CASE STUDY IN BERENDINA1 IN SRI LANKA

Microfinance has played a significant role in poverty reduction in Sri Lanka throughout the last decades. Although studies have been conducted all over the world regarding the impact of microfinance on poor rural households; referring to Sri Lankan context, the impact of microfinance on poor are less documented. Therefore, this study was conducted to identify the role of microfinance in empowering poor rural households with the objective of assessing the impact of microfinance on micro enterprises, assessing the impact of microfinance on household level improvement and to identify the areas to be improved in the current institutional practices. The study was conducted with reference to Galigamuwa Branch in Kegalle District of Brenendina Micro Investments Company Limited with a sample of 126 clients selected using multi stage cluster random sampling technique. The data collection employed a pre- structured questionnaire and collected data were analyzed descriptively. The findings of the study revealed that Berendina Micro Investments Company Limited adopted credit-plus approach in microfinance to serve its clients in the modes of loans and enterprise development services. The clients were empowered socio-economically with the effect of microfinance credit-plus approach through starting and expanding microenterprises in different sectors generating different types of employment opportunities as well as improving basic facilities at household levels including essential infrastructure facilities. Further, the study identified necessary changes to be made in the current practices of credit program and enterprise development program with reference to clients’ perception that will guide the institution towards providing a better service to its clients in the future.Keywords: Enterprise development services, loans, microenterprises, microfinance, poor rural household