Anaemia in pregnant women before and after the mandatory fortification of wheat and corn flours with iron

Objective: To estimate the frequency of anaemia in pregnant women before and after the fortification of flours with Fe. Design: Retrospective study developed from secondary data obtained from medical records. Setting: Two health units in Rio de Janeiro, Brazil. Subjects: Socio-economic, demographic, obstetric and Hb concentration data were collected of 778 pregnant women attending prenatal care. Two study groups were created: the first referred to the period before fortification (G1, n 391), including women whose parturition happened before June 2004; and the second referred to the period after fortification (G2, n 387), including women whose last menstrual cycle happened after June 2005. The Hb cut-off point adopted for anaemia diagnosis was <11.0 g/dl. Results: In linear regression models, when Hb concentration was expressed as a dependent variable, women in G2 presented Hb concentration 0.26 g/dl and 0.36 g/dl higher during the second and third trimesters of pregnancy, respectively, compared with G1. In logistic regression models where the dependent variable was anaemia during the second and third trimesters, it was verified that being a member of G2 was a protective factor against anaemia in the third trimester. Regarding the presence of anaemia at any gestational moment, it was verified that being a member of G2 represented a protective factor against anaemia during pregnancy. Conclusions: Results indicate the protective effect of the fortification of flours with Fe in the fight against gestational anaemia, contributing to prevention and control of this nutritional disorder among pregnant women.

Effect of pH, mucin and bovine serum on rifampicin permeability through Caco-2 cells

Rifampicin, a poorly soluble drug, has great importance in therapeutics as it is the main drug used to treat tuberculosis. The characterization of its permeability and the factors that influence it represent an important tool for predicting its bioavailability. Caco-2 cell monolayers were used as models of the intestinal mucosa to assess the uptake and transport of rifampicin and the effects of various experimental conditions were investigated, in order to establish the influence of these variables on rifampicin permeability. Different pHs (5.8, 6.8 and 7.4) in the apical medium, the presence or absence of mucin (3.0% w/v) in the donor site and the presence or absence of bovine serum albumin (4.0% v/v) in the receptor chamber were the evaluated conditions. The quantification of rifampicin in the apical or basolateral chambers was performed by a validated HPLC-UV method. The change in the donor chamber pH showed that permeability values were greater at pH 6.8, although this increase does not result in an alteration of the qualitative classification of rifampicin, which has high permeability. Mucin and bovine serum showed no effects on the permeability of rifampicin at the concentration tested. Overall, the current study suggests that pH, artificial mucin and bovine serum proteins have no influence on rifampicin permeability. Copyright (c) 2012 John Wiley & Sons, Ltd.

Low temperatures reduce skin healing in the Jacaré do Pantanal (Caiman yacare, Daudin 1802)

Studies of skin wound healing in crocodilians are necessary given the frequent occurrence of cannibalism in intensive farming systems. Air temperature affects tissue recovery because crocodilians are ectothermic. Therefore, the kinetics of skin wound healing in Caiman yacare were examined at temperatures of 33°C and 23°C. Sixteen caiman were selected and divided into two groups of eight maintained at 23°C or 33°C. The studied individuals' scars were photographed after 1, 2, 3, 7, 15 and 30 days of the experimental conditions, and samples were collected for histological processing after 3, 7, 15 and 30 days. Macroscopically, the blood clot (heterophilic granuloma) noticeably remained in place covering the wound longer for the caiman kept at 23°C. Microscopically, the temperature of 23°C slowed epidermal migration and skin repair. Comparatively, new blood vessels, labeled using von Willebrand factor (vWF) antibody staining, were more frequently found in the scars of the 33°C group. The collagen fibers in the dermis were denser in the 33°C treatment. Considering the delayed healing at 23°C, producers are recommended to keep wounded animals at 33°C, especially when tanks are cold, to enable rapid wound closure and better repair of collagen fibers because such lesions tend to compromise the use of their skin as leather.

Sviluppo di metodologie di localizzazione nel contesto del Comprehensive Nuclear Test-Ban Treaty

Since the first underground nuclear explosion, carried out in 1958, the analysis of seismic signals generated by these sources has allowed seismologists to refine the travel times of seismic waves through the Earth and to verify the accuracy of the location algorithms (the ground truth for these sources was often known). Long international negotiates have been devoted to limit the proliferation and testing of nuclear weapons. In particular the Treaty for the comprehensive nuclear test ban (CTBT), was opened to signatures in 1996, though, even if it has been signed by 178 States, has not yet entered into force, The Treaty underlines the fundamental role of the seismological observations to verify its compliance, by detecting and locating seismic events, and identifying the nature of their sources. A precise definition of the hypocentral parameters represents the first step to discriminate whether a given seismic event is natural or not. In case that a specific event is retained suspicious by the majority of the State Parties, the Treaty contains provisions for conducting an on-site inspection (OSI) in the area surrounding the epicenter of the event, located through the International Monitoring System (IMS) of the CTBT Organization. An OSI is supposed to include the use of passive seismic techniques in the area of the suspected clandestine underground nuclear test. In fact, high quality seismological systems are thought to be capable to detect and locate very weak aftershocks triggered by underground nuclear explosions in the first days or weeks following the test. This PhD thesis deals with the development of two different seismic location techniques: the first one, known as the double difference joint hypocenter determination (DDJHD) technique, is aimed at locating closely spaced events at a global scale. The locations obtained by this method are characterized by a high relative accuracy, although the absolute location of the whole cluster remains uncertain. We eliminate this problem introducing a priori information: the known location of a selected event. The second technique concerns the reliable estimates of back azimuth and apparent velocity of seismic waves from local events of very low magnitude recorded by a trypartite array at a very local scale. For the two above-mentioned techniques, we have used the crosscorrelation technique among digital waveforms in order to minimize the errors linked with incorrect phase picking. The cross-correlation method relies on the similarity between waveforms of a pair of events at the same station, at the global scale, and on the similarity between waveforms of the same event at two different sensors of the try-partite array, at the local scale. After preliminary tests on the reliability of our location techniques based on simulations, we have applied both methodologies to real seismic events. The DDJHD technique has been applied to a seismic sequence occurred in the Turkey-Iran border region, using the data recorded by the IMS. At the beginning, the algorithm was applied to the differences among the original arrival times of the P phases, so the cross-correlation was not used. We have obtained that the relevant geometrical spreading, noticeable in the standard locations (namely the locations produced by the analysts of the International Data Center (IDC) of the CTBT Organization, assumed as our reference), has been considerably reduced by the application of our technique. This is what we expected, since the methodology has been applied to a sequence of events for which we can suppose a real closeness among the hypocenters, belonging to the same seismic structure. Our results point out the main advantage of this methodology: the systematic errors affecting the arrival times have been removed or at least reduced. The introduction of the cross-correlation has not brought evident improvements to our results: the two sets of locations (without and with the application of the cross-correlation technique) are very similar to each other. This can be commented saying that the use of the crosscorrelation has not substantially improved the precision of the manual pickings. Probably the pickings reported by the IDC are good enough to make the random picking error less important than the systematic error on travel times. As a further justification for the scarce quality of the results given by the cross-correlation, it should be remarked that the events included in our data set don’t have generally a good signal to noise ratio (SNR): the selected sequence is composed of weak events ( magnitude 4 or smaller) and the signals are strongly attenuated because of the large distance between the stations and the hypocentral area. In the local scale, in addition to the cross-correlation, we have performed a signal interpolation in order to improve the time resolution. The algorithm so developed has been applied to the data collected during an experiment carried out in Israel between 1998 and 1999. The results pointed out the following relevant conclusions: a) it is necessary to correlate waveform segments corresponding to the same seismic phases; b) it is not essential to select the exact first arrivals; and c) relevant information can be also obtained from the maximum amplitude wavelet of the waveforms (particularly in bad SNR conditions). Another remarkable point of our procedure is that its application doesn’t demand a long time to process the data, and therefore the user can immediately check the results. During a field survey, such feature will make possible a quasi real-time check allowing the immediate optimization of the array geometry, if so suggested by the results at an early stage.

Räumliche und zeitliche Einbindung einer strukturierten Population der Westlichen Smaragdeidechse (Lacerta bilineata, DAUDIN 1802) im Mittelrheintal

In der vorliegenden Arbeit wurde die räumliche und zeitliche Dynamik einer strukturierten Population der Westlichen Smaragdeidechse (DAUDIN, 1802) im Mittelrheintal zwischen 1997 und 2000 untersucht. Dazu wurden die Teilaspekte der Hibernation, der Thermoregulation und der Raumnutzung der Art analysiert. Die Ergebnisse der Hibernation deuten auf eine hohe Relevanz dieses Jahresabschnitts für die Art in Bezug auf die Verbreitung in Südexponierten Steilhanglagen am Nordrand ihrer Verbreitung hin. Die Hibernationsstandorte unterscheiden sich im Mikroklimaprofil von Trockenmauern und Sommerlöchern. Die Standorte der Hibernation liegen in Zonen höchster Insolation im Untersuchungsgebiet. Die Analyse der Thermoregulation zeigte geschlechtsspezifische und saisonale Unterschiede, die mit den unterschiedlichen Jahresaktivitätszyklen erklärt werden können. Die Weibchen zeigen eine engere Bindung an die klimatischen Entwicklungen von Mirkohabitatstrukturen als die Männchen, was mit endogenen Faktoren zusammenhängen könnte. Die Parallelen und Unterschiede zu anderen Arten werden diskutiert. In der Raumnutzung zeigen sich auch Unterschiede zwischen Männchen und Weibchen, die auch mit den unterschiedlichen Jahresaktivitätszyklen erklärt werden können. Im Frühjahr und im Herbst zeigt die Art eine Bindung an Standorte hoher Insolation im Untersuchungsgebiet, im Sommer dagegen keine. In der Gesamtbetrachtung werden die Ergebnisse in Bezug auf das Verbreitungsbild der Art, Schutzaspekte und Schlüsselfaktoren der Habitatqualität diskutiert.

Tax Treaty Override

What exactly is tax treaty override ? When is it realized ? This thesis, which is the result of a co-directed PhD between the University of Bologna and Tilburg University, gives a deep insight into a topic that has not yet been analyzed in a systematic way. On the contrary, the analysis about tax treaty override is still at a preliminary stage. For this reason the origin and nature of tax treaty override are first of all analyzed in their ‘natural’ context, i.e. within general international law. In order to characterize tax treaty override and deeply understand its peculiarities the evaluation of the effects of general international law on tax treaties based on the OECD Model Convention is a necessary pre-condition. Therefore, the binding effects of an international agreement on state sovereignty are specifically investigated. Afterwards, the interpretation of the OECD Model Convention occupies the main part of the thesis in order to develop an ‘interpretative model’ which can be applied every time a case of tax treaty override needs to be detected. Fictitious income, exit taxes and CFC regimes are analyzed in order to verify their compliance with tax treaties based on the OECD Model Convention and establish when the relevant legislation realizes cases of tax treaty override.

The European External Action Service and the Implementation of the 'Union Method' in European Foreign Policy

The European External Action Service (EEAS or Service) is one of the most significant and most debated innovations introduced by the Lisbon Treaty. This analysis intends to explain the anomalous design of the EEAS in light of its function, which consists in the promotion of external action coherence. Coherence is a principle of the EU legal system, which requires synergy in the external actions of the Union and its Members. It can be enforced only through the coordination of European policy-makers' initiatives, by bridging the gap between the 'Communitarian' and intergovernmental approaches. This is the 'Union method' envisaged by A. Merkel: "coordinated action in a spirit of solidarity - each of us in the area for which we are responsible but all working towards the same goal". The EEAS embodies the 'Union method', since it is institutionally linked to both Union organs and Member States. It is also capable of enhancing synergy in policy management and promoting unity in international representation, since its field of action is delimited not by an abstract concern for institutional balance but by a pragmatic assessment of the need for coordination in each sector. The challenge is now to make sure that this pragmatic approach is applied with respect to all the activities of the Service, in order to reinforce its effectiveness. The coordination brought by the EEAS is in fact the only means through which a European foreign policy can come into being: the choice is not between the Community method and the intergovernmental method, but between a coordinated position and nothing at all.

In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors

The gastrin-releasing peptide receptor (GRPR) is overexpressed on a number of human tumors and has been targeted with radiolabeled bombesin analogues for the diagnosis and therapy of these cancers. Seven bombesin analogues containing various linkers and peptide sequences were designed, synthesized, radiolabeled with (18)F, and characterized in vitro and in vivo as potential PET imaging agents. Binding studies displayed nanomolar binding affinities toward human GRPR for all synthesized bombesin analogues. Two high-affinity peptide candidates 6b (K(i) = 0.7 nM) and 7b (K(i) = 0.1 nM) were chosen for further in vivo evaluation. Both tracers revealed specific uptake in GRPR-expressing PC-3 tumors and the pancreas. Compared to [(18)F]6b, compound [(18)F]7b was characterized by superior tumor uptake, higher specificity of tracer uptake, and more favorable tumor-to-nontarget ratios. In vivo PET imaging allowed for the visualization of PC-3 tumor in nude mice suggesting that [(18)F]7b is a promising PET tracer candidate for the diagnosis of GRPR-positive tumors in humans.

One-Step (18)F-Labeling of Carbohydrate-Conjugated Octreotate-Derivatives Containing a Silicon-Fluoride-Acceptor (SiFA): In Vitro and in Vivo Evaluation as Tumor Imaging Agents for Positron Emission Tomography (PET)

The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main drawback of the SiFA technology for the synthesis of PET-radiotracers is the high lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac?AcNH-?-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high yields (38 ± 4%) and specific activities between 29 and 56 GBq/?mol in short synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the synthesized conjugates displayed a sst2 receptor affinity (IC?? = 3.3 ± 0.3 nM) comparable to that of somatostatin-28. As a measure of lipophilicity of the conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate and 1.23 for SiFA-Asn(AcNH-?-Glc)-Tyr³-octreotate, which is considerably lower than for SiFA-Tyr³-octreotate (log P(ow) = 1.59). The initial in vivo evaluation of [¹?F]SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate revealed a significant uptake of radiotracer in the tumor tissue of AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that the high lipophilicity of the SiFA moiety can be compensated by applying hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide could successfully be used for receptor imaging for the first time in this proof of concept study.

Regulation of GPCR signaling in hypertension

Hypertension represents a complex, multifactorial disease and contributes to the major causes of morbidity and mortality in industrialized countries: ischemic and hypertensive heart disease, stroke, peripheral atherosclerosis and renal failure. Current pharmacological therapy of essential hypertension focuses on the regulation of vascular resistance by inhibition of hormones such as catecholamines and angiotensin II, blocking them from receptor activation. Interaction of G-protein coupled receptor kinases (GRKs) and regulator of G-protein signaling (RGS) proteins with activated G-protein coupled receptors (GPCRs) effect the phosphorylation state of the receptor leading to desensitization and can profoundly impair signaling. Defects in GPCR regulation via these modulators have severe consequences affecting GPCR-stimulated biological responses in pathological situations such as hypertension, since they fine-tune and balance the major transmitters of vessel constriction versus dilatation, thus representing valuable new targets for anti-hypertensive therapeutic strategies. Elevated levels of GRKs are associated with human hypertensive disease and are relevant modulators of blood pressure in animal models of hypertension. This implies therapeutic perspective in a disease that has a prevalence of 65million in the United States while being directly correlated with occurrence of major adverse cardiac and vascular events. Therefore, therapeutic approaches using the inhibition of GRKs to regulate GPCRs are intriguing novel targets for treatment of hypertension and heart failure.

Tempering the EU? NGO Advocacy in the Area of Freedom, Security, and Justice

The European Union’s (EU) area of Freedom, Security and Justice (AFSJ) portfolio comprises policy areas such as immigration and asylum, and police and judicial cooperation. Steps were taken to bring this field into the mandate of the EU first by the Maastricht Treaty, followed by changes implemented by the Amsterdam and Lisbon Treaties, the last one ‘normalizing’ the EU’s erstwhile Third Pillar. As the emergent EU regime continues to consolidate in this field, NGOs of various kinds continue to seek to influence policy-making and implementation, with varying success. This article seeks to establish the context in which NGOs carry out their work and argues that the EU-NGO interface is impacted both by the institutional realities of the European Union and the capacities of EU-oriented NGOs to seize and expand opportunities for access and input into the policy cycle. Using EU instruments representing three different policy bundles in AFSJ (immigration, asylum and judicial cooperation in criminal matters), the article seeks to map out NGO strategies in engaging and oftentimes resisting European Union policy instruments.

Contamination of Alpine snow and ice at Colle Gnifetti, Swiss/Italian Alps, from nuclear weapons tests

Plutonium is present in the environment as a consequence of atmospheric nuclear tests, nuclear weapons production and industrial releases over the past 50 years. To study temporal trends, a high resolution Pu record was obtained by analyzing 52 discrete samples of an alpine firn/ice core from Colle Gnifetti (Monte Rosa, 4450 m a.s.l.), dating from 1945 to 1990. The 239Pu signal was recorded directly, without decontamination or preconcentration steps, using an Inductively Coupled Plasma - Sector Field Mass Spectrometer (ICP-SFMS) equipped with an high efficiency sample introduction system, thus requiring much less sample preparation than previously reported methods. The 239Pu profile reflects the three main periods of atmospheric nuclear weapons testing: the earliest peak lasted from 1954/55 to 1958 and was caused by the first testing period reaching a maximum in 1958. Despite a temporary halt of testing in 1959/60, the Pu concentration decreased only by half with respect to the 1958 peak due to long atmospheric residence times. In 1961/62 Pu concentrations rapidly increased reaching a maximum in 1963, which was about 40% more intense than the 1958 peak. After the signing of the "Limited Test Ban Treaty" between USA and USSR in 1964, Pu deposition decreased very sharply reaching a minimum in 1967. The third period (1967-1975) is characterized by irregular Pu concentrations with smaller peaks (about 20-30% of the 1964 peak) which might be related to the deposition of Saharan dust contaminated by the French nuclear tests of the 1960s. The data presented are in very good agreement with Pu profiles previously obtained from the Col du Dome ice core (by multi-collector ICP-MS) and Belukha ice core (by Accelerator Mass Spectrometry, AMS). Although a semi-quantitative method was employed here, the results are quantitatively comparable to previously published results.