Ibuprofen-loaded calcium phosphate granules : combination of innovative characterization methods to relate mechanical strength to drug location

This paper studies the impact of the location of a drug substance on the physicochemical and mechanical properties of two types of calcium phosphate granules loaded with seven different contents of ibuprofen, ranging from 1.75% to 46%. These implantable agglomerates were produced by either low or high shear granulation. Unloaded Mi-Pro pellets presented higher sphericity and mechanical properties, but were slightly less porous than Kenwood granules (57.7% vs 61.2%). Nevertheless, the whole expected quantity of ibuprofen could be integrated into both types of granules. A combination of surface analysis, using near-infrared (NIR) spectroscopy coupling chemical imaging, and pellet porosity, by mercury intrusion measurements, allowed ibuprofen to be located. It was shown that, from 0% to 22% drug content, ibuprofen deposited simultaneously on the granule surface, as evidenced by the increase in surface NIR signal, and inside the pores, as highlighted by the decrease in pore volume. From 22%, porosity was almost filled, and additional drug substance coated the granule surfaces, leading to a large increase in the surface NIR signal. This coating was more regular for Mi-Pro pellets owing to their higher sphericity and greater surface deposition of drug substance. Unit crush tests using a microindenter revealed that ibuprofen loading enhanced the mechanical strength of granules, especially above 22% drug content, which was favorable to further application of the granules as a bone defect filler

Structure and Spin Dynamics of La0.85_{0.85}Sr0.15_{0.15}MnO3_3

Neutron scattering has been used to study the structure and spin dynamics of La$_{0.85}$Sr$_{0.15}$MnO$_3$. The magnetic structure of this system is ferromagnetic below T_C = 235 K. We see anomalies in the Bragg peak intensities and new superlattice peaks consistent with the onset of a spin-canted phase below T_{CA} = 205 K, which appears to be associated with a gap at q = (0, 0, 0.5) in the spin-wave spectrum. Anomalies in the lattice parameters indicate a concomitant lattice distortion. The long-wavelength magnetic excitations are found to be conventional spin waves, with a gapless (< 0.02 meV) isotropic dispersion relation $E = Dq^2$. The spin stiffness constant D has a $T^{5/2}$ dependence at low T, and the damping at small q follows $q^4T^{2}$. An anomalously strong quasielastic component, however, develops at small wave vector above 200 K and dominates the fluctuation spectrum as T -> T_C. At larger q, on the other hand, the magnetic excitations become heavily damped at low temperatures, indicating that spin waves in this regime are not eigenstates of the system, while raising the temperature dramatically increases the damping. The strength of the spin-wave damping also depends strongly on the symmetry direction in the crystal. These anomalous damping effects are likely due to the itinerant character of the $e_g$ electrons.Comment: 8 pages (RevTex), 9 figures (encapsulated postscript

Insulin-like growth factor II prevents oxidative and neuronal damage in cellular and mice models of Parkinson's disease

Oxidative distress and mitochondrial dysfunction, are key factors involved in the pathophysiology of Parkinson's disease (PD). The pleiotropic hormone insulin-like growth factor II (IGF-II) has shown neuroprotective and antioxidant effects in some neurodegenerative diseases. In this work, we demonstrate the protective effect of IGF-II against the damage induced by 1-methyl-4-phenylpyridinium (MPP+) in neuronal dopaminergic cell cultures and a mouse model of progressive PD. In the neuronal model, IGF-II counteracts the oxidative distress produced by MPP + protecting dopaminergic neurons. Improved mitochondrial function, increased nuclear factor (erythroid-derived 2)-like2 (NRF2) nuclear translocation along with NRF2-dependent upregulation of antioxidative enzymes, and modulation of mammalian target of rapamycin (mTOR) signalling pathway were identified as mechanisms leading to neuroprotection and the survival of dopaminergic cells. The neuroprotective effect of IGF-II against MPP + -neurotoxicity on dopaminergic neurons depends on the specific IGF-II receptor (IGF-IIr). In the mouse model, IGF-II prevents behavioural dysfunction and dopaminergic nigrostriatal pathway degeneration and mitigates neuroinflammation induced by MPP+. Our work demonstrates that hampering oxidative stress and normalising mitochondrial function through the interaction of IGF-II with its specific IGF-IIr are neuroprotective in both neuronal and mouse models. Thus, the modulation of the IGF-II/IGF-IIr signalling pathway may be a useful therapeutic approach for the prevention and treatment of PD

The camera of the fifth H.E.S.S. telescope. Part I: System description

In July 2012, as the four ground-based gamma-ray telescopes of the H.E.S.S. (High Energy Stereoscopic System) array reached their tenth year of operation in Khomas Highlands, Namibia, a fifth telescope took its first data as part of the system. This new Cherenkov detector, comprising a 614.5 m^2 reflector with a highly pixelized camera in its focal plane, improves the sensitivity of the current array by a factor two and extends its energy domain down to a few tens of GeV. The present part I of the paper gives a detailed description of the fifth H.E.S.S. telescope's camera, presenting the details of both the hardware and the software, emphasizing the main improvements as compared to previous H.E.S.S. camera technology.Comment: 16 pages, 13 figures, accepted for publication in NIM

Risk of gastric cancer in the environs of industrial facilities in the MCC-Spain study

Background: Gastric cancer is the fifth most frequent tumor worldwide. In Spain, it presents a large geographic variability in incidence, suggesting a possible role of environmental factors in its etiology. Therefore, epidemiologic research focused on environmental exposures is necessary. Objectives: To assess the association between risk of gastric cancer (by histological type and tumor site) and residential proximity to industrial installations, according to categories of industrial groups and specific pollutants released, in the context of a population-based multicase-control study of incident cancer conducted in Spain (MCC-Spain). Methods: In this study, 2664 controls and 137 gastric cancer cases from 9 provinces, frequency matched by province of residence, age, and sex were included. Distances from the individuals' residences to the 106 industries located in the study areas were computed. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance (from 1 km to 3 km) to industries, adjusting for matching variables and potential confounders. Results: Overall, no excess risk of gastric cancer was observed in people living close to the industrial installations, with ORs ranging from 0.73 (at ≤2.5 km) to 0.93 (at ≤1.5 km). However, by industrial sector, excess risks (OR; 95%CI) were found near organic chemical industry (3.51; 1.42-8.69 at ≤2 km), inorganic chemical industry (3.33; 1.12-9.85 at ≤2 km), food/beverage sector (2.48; 1.12-5.50 at ≤2 km), and surface treatment using organic solvents (3.59; 1.40-9.22 at ≤3 km). By specific pollutant, a statistically significant excess risk (OR; 95%CI) was found near (≤3 km) industries releasing nonylphenol (6.43; 2.30-17.97) and antimony (4.82; 1.94-12.01). Conclusions: The results suggest no association between risk of gastric cancer and living in the proximity to the industrial facilities as a whole. However, a few associations were detected near some industrial sectors and installations releasing specific pollutants.The authors thank all those who took part in this study by providing questionnaire data. This study was funded by: Scientific Foundation of the Spanish Association Against Cancer (Fundación Científica de la Asociación Española Contra el Cáncer (AECC) e grants EVP-1178/14 and GCTRA18022MORE); “Acción Transversal del Cáncer”, approved on the Spanish Ministry Council on October 11, 2007; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); Spain’s Health Research Fund (Fondo de Investigación Sanitaria - FIS 12/01416); Carlos III Institute of Health (ISCIII) grants, co-funded by ERDF fundsea way to build Europee (grants PI08/0533, PI08/1359, PI08/1770, PS09/00773, PS09/01286, PS09/01662, PS09/01903, PS09/02078, PI11/00226, PI11/01403, PI11/01810, PI11/01889, PI11/02213, PI12/00150, PI12/00265, PI12/00488, PI12/00715, PI12/01270, PI14/00613, PI14/01219, PI15/00069, PI15/00914, PI15/01032, PI17-00092, PI17CIII/00034); the Fundación Marqués de Valdecilla (API 10/09); the Junta de Castilla y León (LE22A10-2); the Consejería de Salud of the Junta de Andalucía (PI-0571-2009, PI-0306-2011, salud201200057018tra); the Conselleria de Sanitat of the Generalitat Valenciana (AP_061/10); the Recercaixa (2010ACUP 00310); the European Commission grants FOOD-CT-2006-036224-HIWATE; the Catalan Government-Agency for Management of University and Research Grants (AGAUR) grants 2017SGR723 and 2014SGR850; the Catalan Government DURSI grant 2014SGR647; the Fundación Caja de Ahorros de Asturias; and the University of Oviedo. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.N

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

One sixth of Amazonian tree diversity is dependent on river floodplains

Amazonia’s floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region’s floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon’s tree diversity and its function

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Reflexión Política. Volumen 5 No. 10 de 2003

La democracia local es tema de la mayor importancia. Las instituciones colombianas desde 1991 la fortalecieron, a efecto de diputar a todo el pueblo para que, en cada lugar, atienda directamente sus propios problemas, y proteja mediante su acción de control administrativo los programas que, el mismo pueblo anhela, y plantea antes de la escogencia de sus mandatarios. En Colombia se está implantando una reforma política que ha modificado el sistema electoral, orientada a fortalecer los partidos políticos, fuentes del poder y sustento de la democracia como sistemaLocal democracy is a matter of the greatest importance. Since 1991, Colombian institutions have strengthened it, in order to deputize all the people so that, in each place, they directly address their own problems, and protect through their action of administrative control the programs that the people themselves long for, and propose before the choice of their leaders. In Colombia, a political reform is being implemented that has modified the electoral system, aimed at strengthening political parties, sources of power and support of democracy as a system