Estimation of reference curves for the urinary steroid metabolome in the first year of life in healthy children : Tracing the complexity of human postnatal steroidogenesis.

CONTEXT: Complex steroid disorders such as P450 oxidoreductase deficiency or apparent cortisone reductase deficiency may be recognized by steroid profiling using chromatographic mass spectrometric methods. These methods are highly specific and sensitive, and provide a complete spectrum of steroid metabolites in a single measurement of one sample which makes them superior to immunoassays. The steroid metabolome during the fetal-neonatal transition is characterized by (a) the metabolites of the fetal-placental unit at birth, (b) the fetal adrenal androgens until its involution 3-6 months postnatally, and (c) the steroid metabolites produced by the developing endocrine organs. All these developmental events change the steroid metabolome in an age- and sex-dependent manner during the first year of life. OBJECTIVE: The aim of this study was to provide normative values for the urinary steroid metabolome of healthy newborns at short time intervals in the first year of life. METHODS: We conducted a prospective, longitudinal study to measure 67 urinary steroid metabolites in 21 male and 22 female term healthy newborn infants at 13 time-points from week 1 to week 49 of life. Urine samples were collected from newborn infants before discharge from hospital and from healthy infants at home. Steroid metabolites were measured by gas chromatography-mass spectrometry (GC-MS) and steroid concentrations corrected for urinary creatinine excretion were calculated. RESULTS: 61 steroids showed age and 15 steroids sex specificity. Highest urinary steroid concentrations were found in both sexes for progesterone derivatives, in particular 20α-DH-5α-DH-progesterone, and for highly polar 6α-hydroxylated glucocorticoids. The steroids peaked at week 3 and decreased by ∼80% at week 25 in both sexes. The decline of progestins, androgens and estrogens was more pronounced than of glucocorticoids whereas the excretion of corticosterone and its metabolites and of mineralocorticoids remained constant during the first year of life. CONCLUSION: The urinary steroid profile changes dramatically during the first year of life and correlates with the physiologic developmental changes during the fetal-neonatal transition. Thus detailed normative data during this time period permit the use of steroid profiling as a powerful diagnostic tool.

Observation of Pulsed γ-Rays Above 25 GeV from the Crab Pulsar with MAGIC

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric γ-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed γ-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

The role of the tourism sector in economic development. Lessons from the Spanish experience

Tourism is one of the most important sectors in the global economy and is considered an efficient tool with which to promote economic growth. The case of Spain¿s economy is well known in this respect; in fact, widespread consensus exists on the part played by tourism in enhancing the industrialisation process in Spain and the part played by foreign currency receipts from tourism in financing the imports of capital goods, which made the expansion of manufacturing possible. This paper aims to assess the real role of foreign currency receipts from tourism in Spain¿s economy from 1960 to the present. The results of Spain¿s experience may well help to guide policy decisions in developing countries in similar circumstances.

The role of the tourism sector in economic development. Lessons from the Spanish experience

Tourism is one of the most important sectors in the global economy and is considered an efficient tool with which to promote economic growth. The case of Spain¿s economy is well known in this respect; in fact, widespread consensus exists on the part played by tourism in enhancing the industrialisation process in Spain and the part played by foreign currency receipts from tourism in financing the imports of capital goods, which made the expansion of manufacturing possible. This paper aims to assess the real role of foreign currency receipts from tourism in Spain¿s economy from 1960 to the present. The results of Spain¿s experience may well help to guide policy decisions in developing countries in similar circumstances.

ESTRO-HERO survey: Radiotherapy equipment and departments in the European countries: Final results from the ESTRO-HERO survey

Background: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries. Methods: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 2629), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO). Results: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.31.5) and 1.4 (range 0.44.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCToption). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT. Conclusions: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT)

ESTRO-HERO survey: Radiotherapy staffing in the European countries: Final results from the ESTRO-HERO survey

Background: The ESTRO Health Economics in Radiation Oncology (HERO) project has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The first milestone was to assess the availability of radiotherapy resources within Europe. This paper presents the personnel data collected in the ESTRO HERO database. Materials and methods: An 84-item questionnaire was sent out to European countries, through their national scientific and professional radiotherapy societies. The current report includes a detailed analysis of radiotherapy staffing (questionnaire items 4760), analysed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis was conducted between February and July 2014, and is based on validated responses from 24 of the 40 European countries defined by the European Cancer Observatory (ECO). Results: A large variation between countries was found for most parameters studied. Averages and ranges for personnel numbers per million inhabitants are 12.8 (2.530.9) for radiation oncologists, 7.6 (019.7) for medical physicists, 3.5 (012.6) for dosimetrists, 26.6 (1.978) for RTTs and 14.8 (0.461.0) for radiotherapy nurses. The combined average for physicists and dosimetrists is 9.8 per million inhabitants and 36.9 for RTT and nurses. Radiation oncologists on average treat 208.9 courses per year (range: 99.9348.8), physicists and dosimetrists conjointly treat 303.3 courses (range: 85757.7) and RTT and nurses 76.8 (range: 25.7156.8). In countries with higher GNI per capita, all personnel categories treat fewer courses per annum than in less affluent countries. This relationship is most evident for RTTs and nurses. Different clusters of countries can be distinguished on the basis of available personnel resources and socio-economic status. Conclusions: The average personnel figures in Europe are now consistent with, or even more favourable than the QUARTS recommendations, probably reflecting a combination of better availability as such, in parallel with the current use of more complex treatments than a decade ago. A considerable variation in available personnel and delivered courses per year however persists among the highest and lowest staffing levels. This not only reflects the variation in cancer incidence and socio-economic determinants, but also the stage in technology adoption along with treatment complexity and the different professional roles and responsibilities within each country. Our data underpin the need for accurate prediction models and long-term education and training programmes

The age of the"Grande Coupure" mammal turnover: New constraints from the Eocene Oligocene record of the Eastern Ebro Basin (NE Spain.)

The Grande Coupure represents a major terrestrial faunal turnover recorded in Eurasia associated with the overall climate shift at the Eocene-Oligocene transition. During this event, a large number of European Eocene endemic mammals became extinct and new Asian immigrants appeared. The absolute age of the Grande Coupure, however, has remained controversial for decades. The Late Eocene-Oligocene continental record of the Eastern Ebro Basin (NE Spain) constitutes a unique opportunity to build a robust magnetostratigraphy- based chronostratigraphy which can contribute with independent age constraints for this important turnover. This study presents new magnetostratigraphic data of a 495-m-thick section (Moià-Santpedor) that ranges from 36.1 Ma to 33.3 Ma. The integration of the new results with previous litho- bio- and magnetostratigraphic records of the Ebro Basin yields accurate ages for the immediately pre- and post-Grand Coupure mammal fossil assemblages found in the study area, bracketing the Grande Coupure to an age embracing the Eocene-Oligocene transition, with a maximum allowable lag of 0.5 Myr with respect to this boundary. The shift to drier conditions that accompanied the global cooling at the Eocene-Oligocene transition probably determined the sedimentary trends in the Eastern Ebro Basin. The occurrence and expansion of an amalgamated-channel sandstone unit is interpreted as the forced response of the fluvial fan system to the transient retraction of the central-basin lake systems. The new results from the Ebro Basin allow us to revisit correlations for the controversial Eocene-Oligocene record of the Hampshire Basin (Isle of Wight, UK), and their implications for the calibration of the Mammal Palaeogene reference levels MP18 to MP21.

Clinical consequences of switching from olanzapine to risperidone and vice versa in outpatients with schizophrenia: 36-month results from the worldwide schizophrenia outpatients health outcomes (W-SOHO) study

BACKGROUND: With many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting. METHODS: W-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162) and vice versa (n=136). Clinical status was assessed at the visit when the first switch was made (i.e. before switching) and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH) overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization). RESULTS: 48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019). Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26), extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89) and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13). No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who switched to olanzapine (difference of 0.29 points, p=0.013). CONCLUSION: Our study showed that patients who switched from risperidone to olanzapine were likely to experience a more favorable treatment course than those who switched from olanzapine to risperidone. Given the nature of observational study design and small sample size, additional studies are warranted.

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Stress testing practices in risk management - Empirical evidence from the Finnish banking and insurance sectors

The main purpose of this study was to analyze how stress tests are used in risk management in the Finnish banking and insurance sectors. In order to enhance understanding of the topic, stress testing was explored in the context of corporate governance and regulato-ry implications of Basel II and Solvency II on stress testing were examined. In addition, the effects of the global financial crisis on stress testing were mapped and the differences in stress testing practices between the banking and insurance sector were discussed. The research method was qualitative case study and it was conducted by interviewing risk managers from ten institutions and a representative from FIN-FSA. Findings pointed out that stress testing practices vary significantly between different institutions. Interesting observations were made in terms of stress testing practices in the banking and insurance sectors. The increasing importance and use of stress tests were recognized as a result of the financial crisis. Stress testing was even considered more like art than science given the amount of challenges it involves. In general, improvements in stress tests were suggested, with an emphasis on stress concentration between different types of risks.

Estimation of alluvial recharge in the semiarid

In areas where there is irrigated agriculture, the recuperation of water reserves in alluvial aquifers may occur preferentially due to precipitation. Recharging can be evaluated from variation information of water depth measured in piezometers or observation wells. Thus, the aim of this research is to study the recharge in the alluvial aquifer formed by the Mimoso temporary stream in the semiarid region of Pernambuco (PE), Brazil, using the method of the fluctuation of the water level. This system is typical on the Brazilian Northeast semiarid region, using groundwater for domestic supply and for irrigation on small scale agriculture. Monthly potentiometric levels and rainfall data were used. The selected period for the study, from January 2002 to October 2009, involved extreme events of flooding and droughts as well as regular years, providing a better understanding of the behavior of the alluvial recharge. It was found that the system responds significantly to precipitation events. It was also observed that even with different soil textures in the study area, recharge factors were not significantly different. The study provided a better understanding of the behavior of aquifer recharge and its relationship with the soil and the rainfall events in the region.

Towards a Strategic Sales Channel Partnership: A Case Study from the IT Services Industry

Strategic partnerships have become a key to competitive advantage and success in a dynamic, global business environment. Partnering provides a strategic response to complex offerings that need multiple sources of technology and knowledge, allowing companies to offer a wider range of services and solutions to meet their customers’ needs. Companies that collaborate with strategic partners in sales channels may significantly grow their business and improve their prospects of winning major contracts. As a consequence, companies are increasingly transforming their go-to-market strategies and sales channel structures to align with the need to create added value to customers together with a business partner. The research objective of this case study is to review and assess the success of an established sales channel partnership in IT services industry and to find ways how to develop it towards a strategic collaboration. The research consists of two main parts. The first part reviews the literature, concluding with the identification of the critical success factors for partnering. The second part sets out for the case findings, focusing on how the success of the established sales channel partnership is perceived by key executives within the partner organizations, and further what actions are required to make the sales channel partnership and joint go-to-market more strategic.

The us subprime crisis and stock market integration: evidence from the BRICS

The aim of this study is to examine the level of stock market co-movement in the BRICS countries and three major industrialized countries (Japan, UK and USA). While analyzing the interdependence and integration of markets, two subsets are examined: before (2000 – 2007) and during the global financial crisis (2007-2011). Generally, interdependence across markets is likely to increase during a highly volatile period. This is problematic because if it were true, the main benefit of international diversification would be reduced at times when it is most needed. The results reveal the dominant role of the US financial markets over the examined time period. Empirical studies of this research paper indicate that cross-market linkages have become slightly stronger during the ongoing subprime crisis than before crisis. However, results also show that an investor may obtain some international diversification benefits by investing especially in the BRICS countries despite the fact of unstable economic condition and growing globalization.

Model-based estimation of liquid flows in the blast furnace hearth and taphole

This thesis presents a set of methods and models for estimation of iron and slag flows in the blast furnace hearth and taphole. The main focus was put on predicting taphole flow patterns and estimating the effects of various taphole conditions on the drainage behavior of the blast furnace hearth. All models were based on a general understanding of the typical tap cycle of an industrial blast furnace. Some of the models were evaluated on short-term process data from the reference furnace. A computational fluid dynamics (CFD) model was built and applied to simulate the complicated hearth flows and thus to predict the regions of the hearth exerted to erosion under various operating conditions. Key boundary variables of the CFD model were provided by a simplified drainage model based on the first principles. By examining the evolutions of liquid outflow rates measured from the furnace studied, the drainage model was improved to include the effects of taphole diameter and length. The estimated slag delays showed good agreement with the observed ones. The liquid flows in the taphole were further studied using two different models and the results of both models indicated that it is more likely that separated flow of iron and slag occurs in the taphole when the liquid outflow rates are comparable during tapping. The drainage process was simulated with an integrated model based on an overall balance analysis: The high in-furnace overpressure can compensate for the resistances induced by the liquid flows in the hearth and through the taphole. Finally, a recently developed multiphase CFD model including interfacial forces between immiscible liquids was developed and both the actual iron-slag system and a water-oil system in laboratory scale were simulated. The model was demonstrated to be a useful tool for simulating hearth flows for gaining understanding of the complex phenomena in the drainage of the blast furnace.