Neoplastic Brain, Glioblastoma, and Immunotherapy

IGF-I, insulin-like growth factor 1, is present in normal fetal/neonatal brain development and reappears in the mature brain participating in the development of malignant tumor, glioblastoma multiforme. Targeting the IGF-I system has emerged as a useful method to reduce glial malignant development. Downregulation in the expression of IGF-I using antigene anti-IGF-I technology (antisense, AS, and triple helix, TH) applied in glioma cell culture established from glioblastoma biopsies induces the expression of B7 and MHC-I antigens in transfected cells (immunogenicity). The transfected cancer cells, “vaccines,” after subcutaneous injection, initiated an immune response mediated by T CD8+ lymphocytes, followed by tumor regression (immunotherapy). The median survival of patients treated by surgery followed by radiotherapy and immunotherapy was 21–24 months. On the other side, the experimental work has demonstrated that IGF-I AS or TH transfected tumor cells fused with activated dendritic cells, DC, showing more striking immunogenic character. Using IGF-I TH/DC “vaccination,” the efficiency in suppressing rat glioma tumors is not only relatively higher than that obtained using IGF-I TH cells but is also more rapid

Impact Evaluation of Training Natural Leaders during a Community-Led Total Sanitation Intervention: A Cluster-Randomized Field Trial in Ghana

We used a cluster-randomized field trial to evaluate training natural leaders (NLs) as an addition to a community-led total sanitation (CLTS) intervention in Ghana. NLs are motivated community members who influence their peers’ behaviors during CLTS. The outcomes were latrine use and quality, which were assessed from surveys and direct observation. From October 2012, Plan International Ghana (Plan) implemented CLTS in 60 villages in three regions in Ghana. After 5 months, Plan trained eight NLs from a randomly selected half of the villages, then continued implementing CLTS in all villages for 12 more months. The NL training led to increased time spent on CLTS by community members, increased latrine construction, and a 19.9 percentage point reduction in open defecation (p < 0.001). The training had the largest impact in small, remote villages with low exposure to prior water and sanitation projects, and may be most effective in socially cohesive villages. For both interventions, latrines built during CLTS were less likely to be constructed of durable materials than pre-existing latrines, but were equally clean, and more often had handwashing materials. CLTS with NL training contributes to three parts of Goal 6 of the Sustainable Development Goals: eliminating open defecation, expanding capacity-building, and strengthening community participation

Discovery of the Optical Transient of the Gamma Ray Burst 990308

The optical transient of the faint Gamma Ray Burst 990308 was detected by the QUEST camera on the Venezuelan 1-m Schmidt telescope starting 3.28 hours after the burst. Our photometry gives $V = 18.32 \pm 0.07$, $R = 18.14 \pm 0.06$, $B = 18.65 \pm 0.23$, and $R = 18.22 \pm 0.05$ for times ranging from 3.28 to 3.47 hours after the burst. The colors correspond to a spectral slope of close to $f_{\nu} \propto \nu^{1/3}$. Within the standard synchrotron fireball model, this requires that the external medium be less dense than $10^{4} cm^{-3}$, the electrons contain $> 20$ of the shock energy, and the magnetic field energy must be less than 24% of the energy in the electrons for normal interstellar or circumstellar densities. We also report upper limits of $V > 12.0$ at 132 s (with LOTIS), $V > 13.4$ from 132-1029s (with LOTIS), $V > 15.3$ at 28.2 min (with Super-LOTIS), and a 8.5 GHz flux of $< 114 \mu Jy$ at 110 days (with the Very Large Array). WIYN 3.5-m and Keck 10-m telescopes reveal this location to be empty of any host galaxy to $R > 25.7$ and $K > 23.3$. The lack of a host galaxy likely implies that it is either substantially subluminous or more distant than a red shift of $\sim 1.2$.Comment: ApJ Lett submitted, 5 pages, 2 figures, no space for 12 coauthor

On Solving the Coronal Heating Problem

This article assesses the current state of understanding of coronal heating, outlines the key elements of a comprehensive strategy for solving the problem, and warns of obstacles that must be overcome along the way.Comment: Accepted by Solar Physics; Published by Solar Physic

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems

Introducing small DNA molecules (Dbait) impairs the repair of damaged chromosomes and provides a new method for enhancing the efficiency of radiotherapy in radio-resistant tumors. The radiosensitizing activity is dependent upon the efficient delivery of Dbait molecules into the tumor cells. Different strategies have been compared, to improve this key step. We developed a pipeline of assays to select the most efficient nanoparticles and administration protocols before preclinical assays: (i) molecular analyses of complexes formed with Dbait molecules, (ii) cellular tests for Dbait uptake and activity, (iii) live zebrafish embryo confocal microscopy monitoring for in vivo distribution and biological activity of the nanoparticles and (iv) tumor growth and survival measurement on mice with xenografted tumors. Two classes of nanoparticles were compared, polycationic polymers with linear or branched polyethylenimine (PEI) and covalently attached cholesterol (coDbait). The most efficient Dbait transfection was observed with linear PEI complexes, in vitro and in vivo. Doses of coDbait ten-fold higher than PEI/Dbait nanoparticles, and pretreatment with chloroquine, were required to obtain the same antitumoral effect on xenografted melanoma. However, with a 22-fold lower ‘efficacy dose/toxicity dose' ratio as compared with Dbait/PEI, coDbait was selected for clinical trials

A hot mini-Neptune in the radius valley orbiting solar analogue HD 110113

We report the discovery of HD 110113 b (TESS object of interest-755.01), a transiting mini-Neptune exoplanet on a 2.5-d orbit around the solar-analogue HD 110113 (Teff = 5730 K). Using TESS photometry and High Accuracy Radial velocity Planet Searcher (HARPS) radial velocities gathered by the NCORES program, we find that HD 110113 b has a radius of 2.05 ± 0.12 R⊕ and a mass of 4.55 ± 0.62 M⊕. The resulting density of $2.90^{+0.75}_{-0.59}$ g cm-3 is significantly lower than would be expected from a pure-rock world; therefore HD 110113 b must be a mini-Neptune with a significant volatile atmosphere. The high incident flux places it within the so-called radius valley; however, HD 110113 b was able to hold on to a substantial (0.1-1 per cent) H-He atmosphere over its ∼4 Gyr lifetime. Through a novel simultaneous Gaussian process fit to multiple activity indicators, we were also able to fit for the strong stellar rotation signal with period 20.8 ± 1.2 d from the RVs and confirm an additional non-transiting planet, HD 110113 c, which has a mass of 10.5 ± 1.2 M⊕ and a period of $6.744^{+0.008}_{-0.009}$ d.Fil: Osborn, H. P.. University of Bern; Suiza. Massachusetts Institute of Technology; Estados UnidosFil: Armstrong, D. J.. University of Warwick; Reino UnidoFil: Adibekyan, V.. Universidad de Porto; PortugalFil: Collins, K. A.. Harvard-Smithsonian Center for Astrophysics; Estados UnidosFil: Delgado Mena, E.. Universidad de Porto; PortugalFil: Howell, S. B.. National Aeronautics and Space Administration; Estados UnidosFil: Hellier, C.. Keele University. Faculty Of Humanities And Social Sciences.; Reino UnidoFil: King, G. W.. University of Warwick; Reino UnidoFil: Lillo Box, J.. Consejo Superior de Investigaciones Cientificas. Centro de Astrobiologia.; EspañaFil: Nielsen, Louise D.. Universidad de Ginebra; SuizaFil: Otegi, J. F.. Universidad de Ginebra; SuizaFil: Santos, N. C.. Universidad de Porto; PortugalFil: Ziegler, C.. University of Toronto; CanadáFil: Anderson, D. R.. University of Warwick; Reino UnidoFil: Briceno, C.. Cerro Tololo Inter American Observatory; ChileFil: Burke, C.. Massachusetts Institute of Technology; Estados UnidosFil: Bayliss, D.. University of Warwick; Reino UnidoFil: Barrado, D.. Consejo Superior de Investigaciones Cientificas. Centro de Astrobiologia.; EspañaFil: Bryant, E. M.. University of Warwick; Reino UnidoFil: Brown, D. J. A.. University of Warwick; Reino UnidoFil: Barros, S. C. C.. Universidad de Porto; PortugalFil: Bouchy, F.. Universidad de Ginebra; SuizaFil: Caldwell, D. A.. SETI Institute; Estados UnidosFil: Conti, D. M.. American Association of Variable Star Observers; Estados UnidosFil: Diaz, Rodrigo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Ciencias Físicas. - Universidad Nacional de San Martín. Instituto de Ciencias Físicas; Argentina. International Center for Advanced Studies; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro Internacional de Estudios Avanzados; ArgentinaFil: Dragomir, D.. University of New Mexico; Estados UnidosFil: Deleuil, M.. Universidad de Aix-Marsella; Francia. Centre National de la Recherche Scientifique; FranciaFil: Demangeon, O. D. S.. Universidad de Porto; PortugalFil: Dorn, C.. Universitat Zurich; SuizaFil: Daylan, T.. Massachusetts Institute of Technology; Estados Unido

New Quasars Detected via Variability in the QUEST1 Survey

By observing the high galactic latitude equatorial sky in drift scan mode with the QUEST (QUasar Equatorial Survey Team) Phase 1 camera, multi-bandpass photometry on a large strip of sky, resolved over a large range of time scales (from hourly to biennially) has been collected. A robust method of ensemble photometry revealed those objects within the scan region that fluctuate in brightness at a statistically significant level. Subsequent spectroscopic observations of a subset of those varying objects easily discriminated the quasars from stars. For a 13-month time scale, 38% of the previously known quasars within the scan region were seen to vary in brightness and subsequent spectroscopic observation revealed that approximately 7% of all variable objects in the scan region are quasars. Increasing the time baseline to 26 months increased the percentage of previously known quasars which vary to 61% and confirmed via spectroscopy that 7% of the variable objects in the region are quasars. This reinforces previously published trends and encourages additional and ongoing synoptic searches for new quasars and their subsequent analysis. During two spectroscopic observing campaigns, a total of 30 quasars were confirmed, 11 of which are new discoveries and 19 of which were determined to be previously known. Using the previously cataloged quasars as a benchmark, we have found it possible to better optimize future variability surveys. This paper reports on the subset of variable objects which were spectroscopically confirmed as quasars.Comment: 22 pages, 3 figures, 4 tables. ApJ, submitted revised version: 19 pages, 4 figures, 2 tables, added clarifications, fixed typos, accepted by ApJ 24 Jan 200

TOI-4336 A b:A temperate sub-Neptune ripe for atmospheric characterization in a nearby triple M-dwarf system

Small planets transiting bright nearby stars are essential to our understanding of the formation and evolution of exoplanetary systems. However, few constitute prime targets for atmospheric characterization, and even fewer are part of multiple star systems. This work aims to validate TOI-4336 A b, a sub-Neptune-sized exoplanet candidate identified by the TESS space-based transit survey around a nearby M-dwarf. We validate the planetary nature of TOI-4336 A b through the global analysis of TESS and follow-up multi-band high-precision photometric data from ground-based telescopes, medium- and high-resolution spectroscopy of the host star, high-resolution speckle imaging, and archival images. The newly discovered exoplanet TOI-4336 A b has a radius of 2.1±0.1R⊕. Its host star is an M3.5-dwarf star of mass 0.33±0.01M⊙ and radius 0.33±0.02R⊙ member of a hierarchical triple M-dwarf system 22 pc away from the Sun. The planet's orbital period of 16.3 days places it at the inner edge of the Habitable Zone of its host star, the brightest of the inner binary pair. The parameters of the system make TOI-4336 A b an extremely promising target for the detailed atmospheric characterization of a temperate sub-Neptune by transit transmission spectroscopy with JWST

Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services

Background: Emergency department (ED) data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. Methods: A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172) over a three-year period (31st March 2008 to 30th March 2011) to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Results: Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P < 0.001); with male:female ratios increasing on more violent nights. Risks peak at age 18 years. Deprived individuals have greater risks of presenting across all ages (AOR 3.87, 95% CIs 3.82-3.92; P < 0.001). Proportions of assaults from deprived communities increase midweek. Female presentations in affluent areas peak aged 20 years. By age 13, females from deprived communities exceed this peak. Presentations peak on Friday and Saturday nights and the eves of public holidays; the largest peak is on New Year’s Eve. Assaults increase over summer with a nadir in January. Impacts of annual celebrations without holidays vary. Some (Halloween, Guy Fawkes and St Patrick’s nights) see increased assaults while others (St George’s and Valentine’s Day nights) do not. Home nation World Cup football matches are associated with nearly a three times increase in midweek assault presentation. Other football and rugby events examined show no impact. The 2008 Olympics saw assaults fall. The overall calendar model strongly predicts observed presentations (R2 = 0.918; P < 0.001). Conclusions: To date, the role of ED data has focused on helping target nightlife police activity. Its utility is much greater; capable of targeting and evaluating multi-agency life course approaches to violence prevention and optimising frontline resources. National ED data are critical for fully engaging health services in the prevention of violence