Parthenolide Blocks Cocaine’s Effect on Spontaneous Firing Activity of Dopaminergic Neurons in the Ventral Tegmental Area

Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaine’s locomotion effects in a planarian animal model (Pagán et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg significantly blocked cocaine’s inhibitory effect on DA neuronal firing rate and bursting activity (p< 0.05, two way ANOVA). We propose that parthenolide might inhibit cocaine’s effects on VTA DA neurons via its interaction with a common binding site at monoamine transporters. It is suggested that parthenolide could have a potential use as an overdose antidote or therapeutic agent to cocaine intoxication

Characterisation of riverine dissolved organic matter using a complementary suite of chromatographic and mass spectrometric methods

Dissolved organic matter (DOM) plays a fundamental role in nutrient cycling dynamics in riverine systems. Recent research has confirmed that the concentration of riverine DOM is not the only factor regulating its functional significance; the need to define the chemical composition of DOM is a priority. Past studies of riverine DOM rested on bulk quantification, however technological advancements have meant there has been a shift towards analytical methods which allow the characterisation of DOM either at compound class or more recently molecular level. However, it is important to consider that all analytical methods only consider a defined analytical window. Thus, herein, we explore the use of a hierarchy of methods which can be used in combination for the investigation of a wide range of DOM chemistries. By using these methods to investigate the DOM composition of a range of streams draining catchments of contrasting environmental character, a wide range of compounds were identified across a range of polarities and molecular weight, thereby extending the analytical window. Through the elucidation of the DOM character in stream samples, information can be collected about likely the sources of DOM. The identification of individual key compounds within the DOM pool is a key step in the design of robust and informative bioassay experiments, used to understand in-stream ecosystem responses. This is critical if we are to assess the role of DOM as a bioavailable nutrient resource and/or ecotoxicological factor in freshwater

An ACO-based Hyper-heuristic for Sequencing Many-objective Evolutionary Algorithms that Consider Different Ways to Incorporate the DM's Preferences

Many-objective optimization is an area of interest common to researchers, professionals, and practitioners because of its real-world implications. Preference incorporation into Multi-Objective Evolutionary Algorithms (MOEAs) is one of the current approaches to treat Many-Objective Optimization Problems (MaOPs). Some recent studies have focused on the advantages of embedding preference models based on interval outranking into MOEAs; several models have been proposed to achieve it. Since there are many factors influencing the choice of the best outranking model, there is no clear notion of which is the best model to incorporate the preferences of the decision maker into a particular problem. This paper proposes a hyper-heuristic algorithm—named HyperACO—that searches for the best combination of several interval outranking models embedded into MOEAs to solve MaOPs. HyperACO is able not only to select the most appropriate model but also to combine the already existing models to solve a specific MaOP correctly. The results obtained on the DTLZ and WFG test suites corroborate that HyperACO can hybridize MOEAs with a combined preference model that is suitable to the problem being solved. Performance comparisons with other state-of-the-art MOEAs and tests for statistical significance validate this conclusion

Examining national and district-level trends in neonatal health in Peru through an equity lens:A success story driven by political will and societal advocacy

Abstract Background Peru has impressively reduced its neonatal mortality rate (NMR). We aimed, for the period 2000–2013, to: (a) describe national and district NMR variations over time; (b) assess NMR trends by wealth quintile and place of residence; (c) describe evolution of mortality causes; (d) assess completeness of registered mortality; (e) assess coverage and equity of NMR-related interventions; and (f) explore underlying driving factors. Methods We compared national NMR time trends from different sources. To describe NMR trends by wealth quintiles, place of residence and districts, we pooled data on births and deaths by calendar year for neonates born to women interviewed in multiple surveys. We disaggregated coverage of NMR-related interventions by wealth quintiles and place of residence. To identify success factors, we ran regression analyses and combined desk reviews with qualitative interviews and group discussions. Results NMR fell by 51 % from 2000 to 2013, second only to Brazil in Latin America. Reduction was higher in rural and poorest segments (52 and 58 %). District NMR change varied by source. Regarding cause-specific NMRs, prematurity decreased from 7.0 to 3.2 per 1,000 live births, intra-partum related events from 2.9 to 1.2, congenital abnormalities from 2.4 to 1.8, sepsis from 1.9 to 0.8, pneumonia from 0.9 to 0.4, and other conditions from 1.2 to 0.7. Under-registration of neonatal deaths decreased recently, more in districts with higher development index and lower rural population. Coverage of family planning, antenatal care and skilled birth attendance increased more in rural areas and in the poorest quintile. Regressions did not show consistent associations between mortality and predictors. During the study period social determinants improved substantially, and dramatic out-of-health-sector and health-sector changes occurred. Rural areas and the poorest quintile experienced greater NMR reduction. This progress was driven, within a context of economic growth and poverty reduction, by a combination of strong societal advocacy and political will, which translated into pro-poor implementation of evidence-based interventions with a rights-based approach. Conclusions Although progress in Peru for reducing NMR has been remarkable, future challenges include closing remaining gaps for urban and rural populations and improving newborn health with qualified staff and intermediate- and intensive-level health facilities

Fabrication of high quality plan-view TEM specimens using the focused ion beam

We describe a technique using a focused ion beam instrument to fabricate high quality plan-view specimens for transmission electron microscopy studies. The technique is simple, site-specific and is capable of fabricating multiple large, &gt;100 μm2 electron transparent windows within epitaxially-grown thin films. A film of La0.67Sr0.33MnO3 is used to demonstrate the technique and its structural and functional properties are surveyed by high resolution imaging, electron spectroscopy, atomic force microscopy and Lorentz electron microscopy. The window is demonstrated to have good thickness uniformity and a low defect density that does not impair the film’s Curie temperature. The technique will enable the study of in–plane structural and functional properties of a variety of epitaxial thin film systems

Renormalization approach for quantum-dot structures under strong alternating fields

We develop a renormalization method for calculating the electronic structure of single and double quantum dots under intense ac fields. The nanostructures are emulated by lattice models with a clear continuum limit of the effective-mass and single-particle approximations. The coupling to the ac field is treated non-perturbatively by means of the Floquet Hamiltonian. The renormalization approach allows the study of dressed states of the nanoscopic system with realistic geometries as well arbitrary strong ac fields. We give examples of a single quantum dot, emphasizing the analysis of the effective-mass limit for lattice models, and double-dot structures, where we discuss the limit of the well used two-level approximation.Comment: 6 pages, 7 figure

Medical oncology future plan of the Spanish Society of Medical Oncology: challenges and future needs of the Spanish oncologists

Purpose: The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. Methods: The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. Results: A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. Conclusions: Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologist’s workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure

Ordering in the dilute weakly-anisotropic antiferromagnet Mn(0.35)Zn(0.65)F2

The highly diluted antiferromagnet Mn(0.35)Zn(0.65)F2 has been investigated by neutron scattering in zero field. The Bragg peaks observed below the Neel temperature TN (approximately 10.9 K) indicate stable antiferromagnetic long-range ordering at low temperature. The critical behavior is governed by random-exchange Ising model critical exponents (nu approximately 0.69 and gamma approximately 1.31), as reported for Mn(x)Zn(1-x)F2 with higher x and for the isostructural compound Fe(x)Zn(1-x)F2. However, in addition to the Bragg peaks, unusual scattering behavior appears for |q|>0 below a glassy temperature Tg approximately 7.0 K. The glassy region T<Tg corresponds to that of noticeable frequency dependence in earlier zero-field ac susceptibility measurements on this sample. These results indicate that long-range order coexists with short-range nonequilibrium clusters in this highly diluted magnet.Comment: 7 pages, 5 figure

Recrystallization of amorphous nano-tracks and uniform layers generated by swift-ion-beam irradiation in lithium niobate.

The thermal annealing of amorphous tracks of nanometer-size diameter generated in lithium niobate (LiNbO3) by Bromine ions at 45 MeV, i.e., in the electronic stopping regime, has been investigated by RBS/C spectrometry in the temperature range from 250°C to 350°C. Relatively low fluences have been used (<1012 cm−2) to produce isolated tracks. However, the possible effect of track overlapping has been investigated by varying the fluence between 3×1011 cm−2 and 1012 cm−2. The annealing process follows a two-step kinetics. In a first stage (I) the track radius decreases linearly with the annealing time. It obeys an Arrhenius-type dependence on annealing temperature with activation energy around 1.5 eV. The second stage (II) operates after the track radius has decreased down to around 2.5 nm and shows a much lower radial velocity. The data for stage I appear consistent with a solid-phase epitaxial process that yields a constant recrystallization rate at the amorphous-crystalline boundary. HRTEM has been used to monitor the existence and the size of the annealed isolated tracks in the second stage. On the other hand, the thermal annealing of homogeneous (buried) amorphous layers has been investigated within the same temperature range, on samples irradiated with Fluorine at 20 MeV and fluences of ∼1014 cm−2. Optical techniques are very suitable for this case and have been used to monitor the recrystallization of the layers. The annealing process induces a displacement of the crystalline-amorphous boundary that is also linear with annealing time, and the recrystallization rates are consistent with those measured for tracks. The comparison of these data with those previously obtained for the heavily damaged (amorphous) layers produced by elastic nuclear collisions is summarily discussed

Applied science facilitates the large-scale expansion of protected areas in an Amazonian hot spot

Meeting international commitments to protect 17% of terrestrial ecosystems worldwide will require \u3e3 million square kilometers of new protected areas and strategies to create those areas in a way that respects local communities and land use. In 2000–2016, biological and social scientists worked to increase the protected proportion of Peru’s largest department via 14 interdisciplinary inventories covering \u3e9 million hectares of this megadiverse corner of the Amazon basin. In each landscape, the strategy was the same: convene diverse partners, identify biological and sociocultural assets, document residents’ use of natural resources, and tailor the findings to the needs of decision-makers. Nine of the 14 landscapes have since been protected (5.7 million hectares of new protected areas), contributing to a quadrupling of conservation coverage in Loreto (from 6 to 23%). We outline the methods and enabling conditions most crucial for successfully applying similar campaigns elsewhere on Earth