Study of the formation of Cu-24at.% Al by reactive milling

In this work, powders of Cu and Al were milled with a proportion equal to 24 atomic % Al, using low and medium energy mills. The initial, intermediate and final stages of the resulting powder are analyzed using scanning electron microscopy, X-ray diffraction and different transmission electron microscopy techniques. The structure and microstructure achieved in each step of the milling process are compared to the results of Cu-16at.%Al and Cu-30at.%Al obtained under the same conditions of reactive milling. At the final stage of milling, it was detected that the obtained intermetallic is not the equilibrium phase of the Cu-Al system.Fil: Giordana, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Muñoz Vásquez, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Garro González, M.. Universidad de Costa Rica; Costa RicaFil: Esquivel, Marcelo Ricardo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; ArgentinaFil: Zelaya, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentin

Report on the evaluation of the IMD programme in Guatemala 2002 - 2003

An external evaluation was carried out in July-August 2003 to assess the results and the implementation process of the first 15 months of IMD’s programme in Guatemala. The central objective of this programme is to strengthen political parties and the party system in a sustainable way. Several unfavourable conditions limit the realisation of this ambition: (i) the political party system in Guatemala has been unstable, fragmented, polarised and discredited, (ii) political parties were often not more than electoral machines, lacking a programmatic and ideological base, and generally figured among the weakest actors in society, (iii) political participation by citizens has been very low, especially among the indigenous majority of the population. Against this background, since March 2002 IMD developed in a joint venture with UNDP an ambitious project for a multiparty dialogue process, trying to generate consensus on a shared National Agenda that reflects the basic principles of the Peace Agreements. The basic idea was that collaboration and dialogue among the parties is a prerequisite for future democratic stability, as none of the individual parties is able to sustain such a national project. Moreover, the national Congress does not function as a forum for dialogue given the polarized political climate in the country...

Intranasal insulin administration decreases cerebral blood flow in cortico‐limbic regions: A neuropharmacological imaging study in normal and overweight males

Aim: To assess and compare the effects of 160 IU intranasal insulin (IN‐INS) administration on regional cerebral blood flow (rCBF) in healthy male individuals with normal weight and overweight phenotypes. / Methods: Thirty young male participants (mean age 25.9 years) were recruited and stratified into two cohorts based on body mass index: normal weight (18.5‐24.9 kg/m2) and overweight (25.0‐29.9 kg/m2). On separate mornings participants received 160 IU of IN‐INS using an intranasal protocol and intranasal placebo as part of a double‐blind crossover design. Thirty minutes following administration rCBF data were collected using a magnetic resonance imaging method called pseudocontinuous arterial spin labelling. Blood samples were collected to assess insulin sensitivity and changes over time in peripheral glucose, insulin and C‐peptide. / Results: Insulin sensitivity did not significantly differ between groups. Compared with placebo, IN‐INS administration reduced rCBF in parts of the hippocampus, insula, putamen, parahippocampal gyrus and fusiform gyrus in the overweight group. No effect was seen in the normal weight group. Insula rCBF was greater in the overweight group versus normal weight only under placebo conditions. Peripheral glucose and insulin levels were not affected by IN‐INS. C‐peptide levels in the normal weight group decreased significantly over time following IN‐INS administration but not placebo. / Conclusion: Insulin‐induced changes within key regions of the brain involved in gustation, memory and reward were observed in overweight healthy male individuals. Following placebo administration, differences in gustatory rCBF were observed between overweight and normal weight healthy individuals

Role of Biomarkers for the Diagnosis of Prion Diseases : A Narrative Review

Prion diseases are progressive and irreversible neurodegenerative disorders with a low incidence (1.5-2 cases per million per year). Genetic (10-15%), acquired (anecdotal) and sporadic (85%) forms of the disease have been described. The clinical spectrum of prion diseases is very varied, although the most common symptoms are rapidly progressive dementia, cerebellar ataxia and myoclonus. Mean life expectancy from the onset of symptoms is 6 months. There are currently diagnostic criteria based on clinical phenotype, as well as neuroimaging biomarkers (magnetic resonance imaging), neurophysiological tests (electroencephalogram and polysomnogram), and cerebrospinal fluid biomarkers (14-3-3 protein and real-time quaking-induced conversion (RT-QuIC)). The sensitivity and specificity of some of these tests (electroencephalogram and 14-3-3 protein) is under debate and the applicability of other tests, such as RT-QuIC, is not universal. However, the usefulness of these biomarkers beyond the most frequent prion disease, sporadic Creutzfeldt-Jakob disease, remains unclear. Therefore, research is being carried out on new, more efficient cerebrospinal fluid biomarkers (total tau, ratio total tau/phosphorylated tau and neurofilament light chain) and potential blood biomarkers (neurofilament light chain, among others) to try to universalize access to early diagnosis in the case of prion diseases

Neural correlates of visuospatial working memory in the ‘at-risk mental state’

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 agematched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis

Carbon/montmorillonite hybrids with different activation methods: adsorption of norfloxacin

Within the group of emerging pollutants, antibiotics have raised scientific concern due to, among others, their negative influenceon the health of living beings. To investigate the adsorption capacity of the antibiotic norfloxacin (NFX), in this workcarbon/montmorillonite hybrid materials (MD) obtained by hydrothermal synthesis using dextrose as carbon source, withacid and thermal activation methods, as well as some precursor materials, were deeply characterized. The characterizationresults of MD showed the presence of carbon at both the interlayer and external surfaces of montmorillonite (M), with anincrease of more than three times in the specific surface area and also in the negative surface electrical charge with respectto M sample. The MD materials assayed were effective (around 40%) to remove NFX from aqueous medium at pH 7, theremoval efficiency being within that of the M (75?99%) and hydrothermal carbon (5%) samples. The XRD and zeta potentialvalues of NFX adsorbed products indicated that, while in M sample the interlayer is the preferential adsorbing surface, forthe MD material assayed (activated with higher acid concentration) the external surface would be the more active.Fil: Zelaya Soulé, María Emilia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Barraqué, Facundo. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Flores, Federico Manuel. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Torres Sánchez, Rosa M.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; ArgentinaFil: Fernández, Mariela A.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Tecnología de Recursos Minerales y Cerámica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Tecnología de Recursos Minerales y Cerámica; Argentin

Characterisation of nasal devices for delivery of insulin to the brain and evaluation in humans using functional magnetic resonance imaging

This study aimed to characterise three nasal drug delivery devices to evaluate their propensity to deliver human insulin solutions to the nasal cavity for redistribution to the central nervous system. Brain delivery was evaluated using functional magnetic resonance imaging to measure regional cerebral blood flow. Intranasal insulin administration has been hypothesised to exploit nose-to-brain pathways and deliver drug directly to the brain tissue whilst limiting systemic exposure. Three nasal pump-actuator configurations were compared for delivery of 400 IU/mL insulin solution by measuring droplet size distribution, plume geometry, spray pattern and in vitro deposition in a nasal cast. The device with optimal spray properties for nose to brain delivery (spray angle between 30° and 45°; droplet size between 20 and 50 μm) also favoured high posterior-superior deposition in the nasal cast and was utilised in a pharmacological magnetic resonance imaging study. Functional magnetic resonance imaging in healthy male volunteers showed statistically significant decreases in regional cerebral blood flow within areas dense in insulin receptors (bilateral amygdala) in response to intranasally administered insulin (160 IU) compared to saline (control). These changes correspond to the expected effects of insulin in the brain and were achieved using a simple nasal spray device and solution formulation. We recommend that a thorough characterisation of nasal delivery devices and qualitative/quantitative assessment of the administered dose is reported in all studies of nose to brain delivery so that responses can be evaluated with respect to posology and comparison between studies is facilitated

“Less is more”: A dose-response account of intranasal oxytocin pharmacodynamics in the human brain

Intranasal oxytocin is attracting attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU), we demonstrate that intranasal oxytocin-induced changes in local regional cerebral blood flow (rCBF) in the amygdala at rest, and in the covariance between rCBF in the amygdala and other key hubs of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects on local rCBF might vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity, which corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain. Data availability: Participants did not consent for open sharing of the data. Therefore, data can only be accessed from the corresponding author upon reasonable reques

Dopaminergic organization of striatum is linked to cortical activity and brain expression of genes associated with psychiatric illness

Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist. Using simultaneous PET-MRI in healthy volunteers, we find strong evidence that patterns of striatal dopamine signaling and cortical blood flow (an index of local neural activity) contain shared information. This shared information links amphetamine-induced changes in gradients of striatal dopamine receptor availability to changes in brain-wide blood flow and is informed by spatial patterns of gene expression enriched for genes implicated in schizophrenia, bipolar disorder, and autism spectrum disorder. These results advance our knowledge of the relationship between cortical function and striatal dopamine, with relevance for understanding pathophysiology and treatment of diseases in which simultaneous aberrations of these systems exist