Determining the activity of Pu-241 by liquid scintillation counting

Liquid scintillation counting (LSC) is one of the most widely used methods for determining the activity of 241Pu. One of the main challenges of this counting method is the efficiency calibration of the system for the low beta energies of 241Pu (Emax = 20.8 keV). In this paper we compare the two most frequently used methods, the CIEMAT/NIST efficiency tracing (CNET) method and the experimental quench correction curve method. Both methods proved to be reliable, and agree within their uncertainties, for the expected quenching conditions of the sources.

Climate change, anthropogenic disturbance and the northward range expansion of Lactuca serriola (Asteraceae)

The distribution range of Lactuca serriola, a species native to the summer-dry mediterranean climate, has expanded northwards during the last 250 years. This paper assesses the influence of climate on the range expansion of this species and highlights the importance of anthropogenic disturbance to its spread. Location Central and Northern Europe. Methods Data on the geographic distribution of L. serriola were assembled through a literature search as well as through floristic and herbarium surveys. Maps of the spread of L. serriola in Central and Northern Europe were prepared based on herbarium data. The spread was assessed more precisely in Germany, Austria and Great Britain by pooling herbarium and literature data. We modelled the bioclimatic niche of the species using occurrence and climatic data covering the last century to generate projections of suitable habitats under the climatic conditions of five time periods. We tested whether the observed distribution of L. serriola could be explained for each time period, assuming that the climatic niche of the species was conserved across time. Results The species has spread northwards since the beginning of the 19th century. We show that climate warming in Europe increased the number of sites suitable for the species at northern latitudes. Until the late 1970s, the distribution of the species corresponded to the climatically suitable sites available. For the last two decades, however, we could not show any significant relationship between the increase in suitable sites and the distributional range change of L. serriola. However, we highlight potential areas the species could spread to in the future (Great Britain, southern Scandinavia and the Swedish coast). It is predominantly non-climatic influences of global change that have contributed to its rapid spread. Main conclusions The observation that colonizing species are not filling their climatically suitable range might imply that, potentially, other ruderal species could expand far beyond their current range. Our work highlights the importance of historical floristic and herbarium data for understanding the expansion of a species. Such historical distributional data can provide valuable information for those planning the management of contemporary environmental problems, such as species responses to environmental change.

Late Pliensbachian-Early Toarcian (Early Jurassic) environmental changes in an epicontinental basin of NW Europe (Causses area, central France): A micropaleontological and geochemical approach

We present an integrated work based on calcareous nannofossil and benthic foraminiferal assemblages, and geochemical analyses of two Upper Pliensbachian-Lower Toarcian sections located in the central-South France. The studied sections, Tournadous and Saint-Paul-des-Fonts, represent the proximal and the distal part, respectively, of the Jurassic Causses Basin, one of the small, partly enclosed basins belonging to the epicontinental shelf of the NW Tethys. At the transition from Late Pliensbachian to Early Toarcian, the Causses Basin recorded an emersion in response to the global sea-level fall. Our data indicate severe environmental conditions of marine waters, including salinity decrease and anoxia development, occurring in the Early Toarcian. The acme of this deterioration coincides with the Early Toarcian Anoxic Event (T-OAE) but, due to the restricted nature of the basin. anoxia persisted until the end of the Early Toarcian. mainly in the deeper parts of the basin. The micronutrients and organic organic-matter fluxes were probably high during the entire studied time interval, as shown by nannofossil and foraminiferal assemblages. However, nannoplankton production drastically decreased during the T-OAE, as demonstrated by very low nannofossil fluxes, and only taxa tolerant to low-saline surface waters could thrive. At the same time, benthic foraminifers temporarily disappeared in response to sea-bottom anoxia. Our study demonstrates that environmental changes related to the T-OAE are well-recorded even in small, partly enclosed basins of NW Europe, like the Causses Basin. Within this area, the effects of global changes. like sea sea-level and temperature fluctuations, are modulated by local conditions mainly controlled by the morphology of the basin. (C) 2008 Elsevier B.V. All rights reserved.

Selective regulation of acid-sensing ion channel 1 by serine proteases.

Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a rapid drop in extracellular pH. Conditions of low extracellular pH, such as ischemia and inflammation in which ASICs are thought to be active, are accompanied by increased protease activity. We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show that protease exposure shifts the pH dependence of ASIC1a activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in current response if ASIC1a is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of approximately 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide evidence that this bi-directional regulation of ASIC1a function also occurs in neurons. Thus, we have identified a mechanism that modulates ASIC function and may allow ASIC1a to adapt its gating to situations of persistent extracellular acidification.

Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice

Background: The transcription factor NFAT5/TonEBP regulates the response of mammalian cells to hypertonicity. However, little is known about the physiopathologic tonicity thresholds that trigger its transcriptional activity in primary cells. Wilkins et al. recently developed a transgenic mouse carrying a luciferase reporter (9xNFAT-Luc) driven by a cluster of NFAT sites, that was activated by calcineurin-dependent NFATc proteins. Since the NFAT site of this reporter was very similar to an optimal NFAT5 site, we tested whether this reporter could detect the activation of NFAT5 in transgenic cells.Results: The 9xNFAT-Luc reporter was activated by hypertonicity in an NFAT5-dependent manner in different types of non-transformed transgenic cells: lymphocytes, macrophages and fibroblasts. Activation of this reporter by the phorbol ester PMA plus ionomycin was independent of NFAT5 and mediated by NFATc proteins. Transcriptional activation of NFAT5 in T lymphocytes was detected at hypertonic conditions of 360–380 mOsm/kg (isotonic conditions being 300 mOsm/kg) and strongly induced at 400 mOsm/kg. Such levels have been recorded in plasma in patients with osmoregulatory disorders and in mice deficient in aquaporins and vasopressin receptor. The hypertonicity threshold required to activate NFAT5 was higher in bone marrow-derived macrophages (430 mOsm/kg) and embryonic fibroblasts (480 mOsm/kg). Activation of the 9xNFAT-Luc reporter by hypertonicity in lymphocytes was insensitive to the ERK inhibitor PD98059, partially inhibited by the PI3-kinase inhibitor wortmannin (0.5 μM) and the PKA inhibitor H89, and substantially downregulated by p38 inhibitors (SB203580 and SB202190) and by inhibition of PI3-kinase-related kinases with 25 μM LY294002. Sensitivity of the reporter to FK506 varied among cell types and was greater in primary T cells than in fibroblasts and macrophages.Conclusion: Our results indicate that NFAT5 is a sensitive responder to pathologic increases in extracellular tonicity in T lymphocytes. Activation of NFAT5 by hypertonicity in lymphocytes was mediated by a combination of signaling pathways that differed from those required in other cell types. We propose that the 9xNFAT-Luc transgenic mouse model might be useful to study the physiopathological regulation of both NFAT5 and NFATc factors in primary cells.

Characterization of the role of AKAP-Lbc/p38 complex in the hypertrophic response of the heart

In response to chronic stress the heart undergoes an adverse remodeling process associated with cardiomyocyte hypertrophy, increased cellular apoptosis and fibrosis, which ultimately causes cardiac dysfunction and heart failure. Increasing evidence suggest the role of scaffolding and anchoring proteins in coordinating different signaling pathways that mediate the hypertrophic response of the heart. In this context, the family of Α-kinase anchoring proteins (AKAPs) emerged as important regulators of the cardiac function. During my thesis work I have conducted two independent projects, both of them aiming at elucidating the role of AKAPs in the heart. It has been shown that AKAP-Lbc, an anchoring protein that possesses an intrinsic Rho- specific exchange factor activity, organizes a signaling complex that links AKAP-Lbc- dependent activation of RhoA with the mitogen activated protein kinase (MAPK) p38. The first aim of my thesis was to study the role of this novel transduction pathway in the context of cardiac hypertrophy. Here we show that transgenic mice overexpressing in cardiomyocytes a competitor fragment of AKAP-Lbc, which specifically disrupts endogenous AKAP-Lbc / p38 complexes, developed early dilated cardiomyopathy in response to two weeks of transverse aortic constriction (TAC) as compared to controls. Interestingly, inhibition of the AKAP-Lbc / p38 transduction pathway significantly reduced the hypertrophic growth of single cardiomyocytes induced by pressure overload. Therefore, it appears that the AKAP- Lbc / p38 complex is crucially involved in the regulation of stress-induced cardiomyocyte hypertrophy and that disruption of this signaling pathway is detrimental for the heart under conditions of sustained hemodynamic stress. Secondly, in order to identify new AKAPs involved in the regulation of cardiac function, we followed a proteomic approach which allowed us to characterize AKAP2 as a major AKAP in the heart. Importantly, here we show that AKAP2 interacts with several proteins known to be involved in the control of gene transcription, such as the nuclear receptor coactivator 3 (NCoA3) or the ATP-dependent SWI/SNF chromatin remodeling complex. Thus, we propose AKAP2 as a novel mediator of cardiac gene expression through its interaction with these transcriptional regulators.

The Nationalism of stateless nations and Europe. The Catalan case

This paper analyzes how the ideas and concepts of Europe have developed in Catalonia, under the conditions of a decentralizing “nation-state” (Spain) on one hand, and the European integration process on the other. It analyzes the programmes, manifestations of political leaders, and political actions of the Catalan political parties, specially the nationalists, from the setting up of the Spanish state of autonomies (1977-1982) until today. The paper tries to show how, in multilevel governance, holistic and enthusiastic visions of an economically and political integrating Europe as a “natural ally” of a Catalan nationalism were partially replaced by more pragmatic and even more critical assessments.

Role of glucagon in disposal of an amino acid load.

Amino acids stimulate the release of glucagon and insulin. To assess the role of aminogenic hyperglucagonemia, we have studied, in healthy young males, the effects of basal (less than 100 pg/ml) and high (200-400 pg/ml) plasma glucagon concentrations on amino acid metabolism during intravenous infusion (0.5 g.h-1.4 h) of a mixture of 15 amino acids. Basal plasma glucagon concentrations were obtained by infusion of somatostatin (0.5 mg/h) plus glucagon (0.25 ng.kg-1.min-1) and high plasma glucagon concentrations by infusion of somatostatin plus glucagon (3.0 ng.kg-1.min-1) or by infusion of amino acids alone. All studies were performed under conditions of euglycemic (83-91 mg/dl) hyperinsulinemia (50-80 microU/ml). Hyperglucagonemia significantly increased 1) net amino acid transport from the extracellular into the intracellular space (by approximately 4%), 2) net degradation of amino acids entering the intracellular space (by approximately 40%), and 3) conversion of degraded amino acids into glucose from 0-10% (basal glucagon) to 70-100% (high glucagon). Hyperglucagonemia did not affect the amount of amino acids excreted in the urine (approximately 4%). We conclude that glucagon plays an important role in the disposition of amino acids by increasing their inward transport, their degradation, and their conversion into glucose.

The pattern of health care use of older prisoners in Switzerland.

Introduction: Population ageing is a worldwide phenomenon that forces us to make radical changes on multiple levels of society. So far, studies have concluded that the health, both physical and mental, of prisoners in general and older prisoners in particular is worse than that of the general population. Prisoners are reported to age faster as compared to adults in the community. However, to date, very little is known about the actual healthcare conditions of older prisoners and almost no substantial knowledge is available concerning their patterns of healthcare use. Method: A quantitative study was conducted in four prisons for male prisoners in Switzerland, including two open and two closed prisons situated in different cantons. In this study, medical records of older prisoners (50+) were obtained from the respective authority upon consent and total anonymity was ensured. Data gathered from all available medical records included basic demographic information, education and prison sentencing. Healthcare data obtained were extensive in nature encompassing data related to illness types, number of visits to different health care providers and hospitals. The corresponding reasons for visits and outcomes of these visits were extracted. All data are analysed using statistical software SPSS 20.0. Results: Data were extracted for a total of 50 older prisoners living in Switzerland. The chosen prisons are located in German-speaking cantons. Preliminary results show that the age average was 56 years. For more than half, this was their first imprisonment. Nevertheless, a third of them were sentenced to measures (Art. 64 Swiss Criminal Code) which means that the length of the detention is indefinite and while release is possible it is in most cases not very likely. This entails that these prisoners will grow old in prison and some will even spend their remaining years there. Concerning their health, a third of the sample reported respiratory and cardiovascular illnesses and half reported suffering from some form of musculoskeletal related pain. Older prisoners were prescribed on average only 3.5 medications, which is significantly fewer than the number of medication prescribed to younger prisoners, whose data were also sampled. Conclusion: Access to healthcare is a right given to all prisoners through the principle of equivalence which is generally exercised in Switzerland. Prisoners growing old in prison will represent a challenge for prison health care services.

Patients' knowledge of Diabetes five years after the end of an educational program

We present a cross-sectional study that aims to describe the sociodemographic and clinical conditions of individuals with diabetes mellitus and to analyze their knowledge of treatment five years after the end of an educational program in which they took part. In 2010, 40 individuals who had participated in a diabetes educational program for 12 months in 2005 at a primary care service were interviewed. A form was used for data collection that included their knowledge of the notion, physiopathology, and treatment of the disease; exercise; nutrition; foot care; self-monitoring of capillary blood glucose at home; hypoglycemia; chronic complications; special situations; and family support. The results showed that the volunteers incorporated the information about the notion, physiopathology, and treatment of the disease; exercise; foot care; self-monitoring; care associated with hypoglycemia; chronic complications; and special situations. In contrast, nutrition and family support require further reinforcement. It is concluded that five years after the end of the educational program, the participants kept most of the information provided.

Predictors of asthma control in everyday clinical practice in Switzerland.

OBJECTIVE: To identify predictors of improved asthma control under conditions of everyday practice in Switzerland. RESEARCH DESIGN AND METHODS: A subgroup of 1380 patients with initially inadequately controlled asthma was defined from a cohort of 1893 asthmatic patients (mean age 45.3 + or - 19.2 years) recruited by 281 office-based physicians who participated in a previously-conducted asthma control survey in Switzerland. Multiple regression techniques were used to identify predictors of improved asthma control, defined as an absolute decrease of 0.5 points or more in the Asthma Control Questionnaire between the baseline (V1) and follow-up visit (V2). RESULTS: Asthma control between V1 and V2 improved in 85.7%. Add-on treatment with montelukast was reported in 82.9% of the patients. Patients with worse asthma control at V1 and patients with good self-reported adherence to therapy had significantly higher chances of improved asthma control (OR = 1.24 and 1.73, 95% CI 1.18-1.29 and 1.20-2.50, respectively). Compared to adding montelukast and continuing the same inhaled corticosteroid/fixed combination (ICS/FC) dose, the addition of montelukast to an increased ICS/FC dose yielded a 4 times higher chance of improved asthma control (OR = 3.84, 95% CI 1.58-9.29). Significantly, withholding montelukast halved the probability of achieving improved asthma control (OR = 0.51, 95% CI = 0.33-078). The probability of improved asthma control was almost 5 times lower among patients in whom FEV(1) was measured compared to those in whom it was not (OR = 0.23, 95% CI = 0.09-0.55). Patients with severe persistent asthma also had a significantly lower probability of improved control (OR = 0.15, 95% CI = 0.07-0.32), as did older patients (OR = 0.98, 95% CI = 0.97-0.99). Subgroup analyses which excluded patients whose asthma may have been misdiagnosed and might in reality have been chronic obstructive pulmonary disease (COPD) showed comparable results. CONCLUSIONS: Under conditions of everyday clinical practice, the addition of montelukast to ICS/FC and good adherence to therapy increased the likelihood of achieving better asthma control at the follow-up visit, while older age and more severe asthma significantly decreased it.

Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets.

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.

Effect of sodium loading/depletion on renal oxygenation in young normotensive and hypertensive men.

The goal of this study was to investigate the effect of sodium intake on renal tissue oxygenation in humans. To this purpose, we measured renal hemodynamics, renal sodium handling, and renal oxygenation in normotensive (NT) and hypertensive (HT) subjects after 1 week of a high-sodium and 1 week of a low-sodium diet. Renal oxygenation was measured using blood oxygen level-dependent magnetic resonance. Tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* values in the medulla and cortex were calculated, with a low R2* indicating a high tissue oxygenation. Ten male NT (mean age: 26.5+/-7.4 years) and 8 matched HT subjects (mean age: 28.8+/-5.7 years) were studied. Cortical R2* was not different under the 2 conditions of salt intake. Medullary R2* was significantly lower under low sodium than high sodium in both NT and HT subjects (28.1+/-0.8 versus 31.3+/-0.6 s(-1); P<0.05 in NT; and 27.9+/-1.5 versus 30.3+/-0.8 s(-1); P<0.05, in HT), indicating higher medullary oxygenation under low-sodium conditions. In NT subjects, medullary oxygenation was positively correlated with proximal reabsorption of sodium and negatively with absolute distal sodium reabsorption, but not with renal plasma flow. In HT subjects, medullary oxygenation correlated with the 24-hour sodium excretion but not with proximal or with the distal handling of sodium. These data demonstrate that dietary sodium intake influences renal tissue oxygenation, low sodium intake leading to an increased renal medullary oxygenation both in normotensive and young hypertensive subjects.

Factors associated with loss of handgrip strength in long-lived elderly

Objective To investigate the prevalence of reduced grip strength and associated factors in long-lived elderly, who are users of primary health care. Method Cross-sectional quantitative study, data were collected during the period of January to December of 2013, by applying tests and questionnaires. The convenience sampling was comprised of 157 seniors. Results The findings indicate that the reduction in grip strength presents a moderate prevalence (25.5%), predominantly among females (19.1%), in the age group of 80-89 years (18.5%) and in those with lower educational levels (15.9%). The association between reduced grip strength and the variables of age and body mass index showed a statistical significance. Conclusion Investigations about the handgrip strength are essential for identifying clinical conditions of Brazilian long-lived elderly, and contribute to the development of plans towards the management of frailty.

Origin of mineralizing fluids of the sediment-hosted Navachab gold mine, Namibia: Constraints from stable (O, H, C, S) isotopes

The Navachab gold mine in the Damara belt of central Namibia is characterized by a polymetallic Au-Bi-As-Cu-Ag ore assemblage, including pyrrhotite, chalcopyrite, sphalerite, arsenopyrite, bismuth, gold, bismuthinite, and bismuth tellurides. Gold is hosted by quartz sulfide veins and semimassive sulfide lenses that are developed in a near-vertical sequence of shelf-type metasedimentary rocks, including marble, calcsilicate rock, and biotite schist. The sequence has been intruded by abundant syntectonic lamprophyre, aplite, and pegmatite dikes, documenting widespread igneous activity coeval with mineralization. The majority of quartz from the veins has delta(18)O values of 14 to 15 per mil (V-SMOW). The total variations in delta(18)O values of the biotite schist and calcsilicate rock are relatively small (12-14 parts per thousand), whereas the marble records steep gradients in delta(18)O values (17-21 parts per thousand), the lowest values being recorded at the vein margins. Despite this, there is no correlation between delta(18)O and delta(13)C values and the carbonate content of the rocks, indicating that fluid-rock interaction alone cannot explain the isotopic gradients. In addition, the marble records increased delta(13)C values at the contact to the veins, possibly related to a change in the physicochemical conditions during fluid-rock interaction. Gold is interpreted to have precipitated in equilibrium with metamorphic find (delta(18)O 12-14 parts per thousand; delta D = -40 to -60 parts per thousand) at peak metamorphic conditions of ca. 550 degrees C and 2 kbars, consistent with isotopic fractionations between coexisting calcite, garnet, and clinopyroxene in the alteration halos. The most likely source of the mineralizing fluid was a midcrustal fluid in equilibrium with the Damaran metapelites that underwent prograde metamorphism at amphibolite- to granulite-facies grades. Although there is no isotopic evidence for the contribution of magmatic fluids, they may have been important in contributing to the overall hydraulic regime and high apparent geothermal gradients (ca. 80 degrees C/km(-1)) in the mine area.