Angiotensin receptor blockers are not associated with reduced inflammatory markers in the general population.

OBJECTIVE: Angiotensin receptor blockers (ARBs) have been suggested to reduce inflammation in randomized controlled trials. We assessed the association between ARBs and inflammatory markers in a general population setting. METHODS: This is a population-based prospective study conducted in Lausanne, Switzerland. Baseline data from 933 participants on antihypertensive drugs (424 on ARBs) was collected in 2003-2006. Follow-up data from 1120 participants (572 on ARBs) was collected in 2009-2012. C-reactive protein (CRP), interleukins 1β and 6 and tumor necrosis factor alpha (TNF-α) were assessed and categorized in quartiles. RESULTS: At baseline, no differences were found between participants taking or not taking ARBs for all inflammatory markers studied, and this association persisted after multivariate adjustment: odds ratios (ORs) and (95% confidence interval) for being in the highest quartile of interleukin-1β, interleukin-6, TNF-α and CRP for participants on ARB compared to participants not on ARB were 1.23 (0.89-1.70), 1.26 (0.93-1.70), 1.14 (0.85-1.53) and 1.27 (0.96-1.69) respectively (P > 0.05). These findings were further replicated in the follow-up study: OR and (95% CI) of 1.10 (0.78-1.55), 0.87 (0.64-1.19), 0.83 (0.61-1.14) and 0.91 (0.68-1.22) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). Finally, no effect of ARBs was found when comparing participants who received ARBs throughout the 5.4-year follow-up with participants on other antihypertensive drugs: OR and (95% CI) of 0.93 (0.61-1.42), 0.80 (0.54-1.17), 0.86 (0.59-1.25) and 0.95 (0.67-1.35) for interleukin-1β, interleukin-6, TNF-α and CRP respectively (P > 0.05). CONCLUSION: ARBs are not associated with reduced levels of inflammatory markers in the general population.

Are Newer AEDs Better Than the Classic Ones in the Treatment of Status Epilepticus?

Several newer antiepileptic drugs have been increasingly used in patients with status epilepticus, especially levetiracetam and lacosamide, because of their intravenous availability. They may offer advantages in terms of tolerability; however, to date, no clear evidence suggests any advantage regarding efficacy after the use of newer antiepileptic drugs in this specific clinical setting. However, there has been a considerable revival of interest regarding some classic compounds, such as midazolam (MDZ), valproate (VPA), ketamine, or ketogenic diet. Awaiting comparative studies, which in part are ongoing, it seems reasonable, for the first choice, to rely on those agents that are best known and less expensive.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

"Hit the primary": A paradigm shift in the treatment of metastatic prostate cancer?

Patients with metastatic prostate cancer (PC) represent a heterogeneous group with survival rates varying between 13 and 75 months. The current standard treatment in this setting is hormonal therapy, with or without docetaxel-based chemotherapy. In the era of individualized medicine, however, maximizing treatment options, especially in long-term surviving patients with limited disease burden, is of capital importance. Emerging data, mainly from retrospective surgical series, show survival benefits in men diagnosed with metastatic PC following definitive therapy for the prostate. Whether the irradiation of primary tumor in a metastatic disease might improve the therapeutic ratio in association with systemic treatments remains investigational. In this scenario, modern radiation therapy (RT) can play a significant role owing to its intrinsic capability to act as a more general immune response modifier, as well as to the potentially better toxicity profile compared to surgery. Preclinical data, clinical experience, and challenges in local treatment in de novo metastatic PC are reviewed and discussed.

A practical guide for the formulation of propositions in the bayesian approach to DNA evidence interpretation in an adversarial environment

The interpretation of complex DNA profiles is facilitated by a Bayesian approach. This approach requires the development of a pair of propositions: one aligned to the prosecution case and one to the defense case. This note explores the issue of proposition setting in an adversarial environment by a series of examples. A set of guidelines generalize how to formulate propositions when there is a single person of interest and when there are multiple individuals of interest. Additional explanations cover how to handle multiple defense propositions, relatives, and the transition from subsource level to activity level propositions. The propositions depend on case information and the allegations of each of the parties. The prosecution proposition is usually known. The authors suggest that a sensible proposition is selected for the defense that is consistent with their stance, if available, and consistent with a realistic defense if their position is not known.

Using computational fluid dynamics to predict head losses in the auxiliary elements of a microirrigation sand filter

It is often assumed that total head losses in a sand filter are solely due to the filtration media and that there are analytical solutions, such as the Ergun equation, to compute them. However, total head losses are also due to auxiliary elements (inlet and outlet pipes and filter nozzles), which produce undesirable head losses because they increase energy requirements without contributing to the filtration process. In this study, ANSYS Fluent version 6.3, a commercial computational fluid dynamics (CFD) software program, was used to compute head losses in different parts of a sand filter. Six different numerical filter models of varying complexities were used to understand the hydraulic behavior of the several filter elements and their importance in total head losses. The simulation results show that 84.6% of these were caused by the sand bed and 15.4% were due to auxiliary elements (4.4% in the outlet and inlet pipes, and 11.0% in the perforated plate and nozzles). Simulation results with different models show the important role of the nozzles in the hydraulic behavior of the sand filter. The relationship between the passing area through the nozzles and the passing area through the perforated plate is an important design parameter for the reduction of total head losses. A reduced relationship caused by nozzle clogging would disproportionately increase the total head losses in the sand filter

Reaction Kinetics and Viscosity Modelling in the Fusion Syntheses of Ca- and Ca/Mg-resinates

Rosin is a natural product from pine forests and it is used as a raw material in resinate syntheses. Resinates are polyvalent metal salts of rosin acids and especially Ca- and Ca/Mg- resinates find wide application in the printing ink industry. In this thesis, analytical methods were applied to increase general knowledge of resinate chemistry and the reaction kinetics was studied in order to model the non linear solution viscosity increase during resinate syntheses by the fusion method. Solution viscosity in toluene is an important quality factor for resinates to be used in printing inks. The concept of critical resinate concentration, c crit, was introduced to define an abrupt change in viscosity dependence on resinate concentration in the solution. The concept was then used to explain the non-inear solution viscosity increase during resinate syntheses. A semi empirical model with two estimated parameters was derived for the viscosity increase on the basis of apparent reaction kinetics. The model was used to control the viscosity and to predict the total reaction time of the resinate process. The kinetic data from the complex reaction media was obtained by acid value titration and by FTIR spectroscopic analyses using a conventional calibration method to measure the resinate concentration and the concentration of free rosin acids. A multivariate calibration method was successfully applied to make partial least square (PLS) models for monitoring acid value and solution viscosity in both mid-infrared (MIR) and near infrared (NIR) regions during the syntheses. The calibration models can be used for on line resinate process monitoring. In kinetic studies, two main reaction steps were observed during the syntheses. First a fast irreversible resination reaction occurs at 235 °C and then a slow thermal decarboxylation of rosin acids starts to take place at 265 °C. Rosin oil is formed during the decarboxylation reaction step causing significant mass loss as the rosin oil evaporates from the system while the viscosity increases to the target level. The mass balance of the syntheses was determined based on the resinate concentration increase during the decarboxylation reaction step. A mechanistic study of the decarboxylation reaction was based on the observation that resinate molecules are partly solvated by rosin acids during the syntheses. Different decarboxylation mechanisms were proposed for the free and solvating rosin acids. The deduced kinetic model supported the analytical data of the syntheses in a wide resinate concentration region, over a wide range of viscosity values and at different reaction temperatures. In addition, the application of the kinetic model to the modified resinate syntheses gave a good fit. A novel synthesis method with the addition of decarboxylated rosin (i.e. rosin oil) to the reaction mixture was introduced. The conversion of rosin acid to resinate was increased to the level necessary to obtain the target viscosity for the product at 235 °C. Due to a lower reaction temperature than in traditional fusion synthesis at 265 °C, thermal decarboxylation is avoided. As a consequence, the mass yield of the resinate syntheses can be increased from ca. 70% to almost 100% by recycling the added rosin oil.

Limnological research in the Iberian Peninsula: a ten-year survey of published literature.

Research on limnology in southern Europe had achieved a notable presence in the international arena before the onset of the current dramatic cuts in public investment in science. We assessed the limnological research published in peer-reviewed journals by Spanish and Portuguese (i.e., Iberian) researchers during the decade prior to the economic recession (2000 to 2009). The Thompson Reuters Web of Knowledge database was used to retrieve all publications on limnology authored by researchers affiliated with Spanish or Portuguese institutions independently of the geographical setting of the study. The publishing pattern was characterised in terms of authors, journals, and citation statistics. In addition, a thematic characterisation of the research was performed by a manual assignation of several categorical descriptors combined with a blind word count analysis. Iberian researchers produced an annual mean of 278 papers on limnology. Papers were published in journals that had impact factors ranging from 0.1 to 31.4, with a mean of 2.0. Based on citations, the impact of the Iberian limnological research was not due to a few highly cited papers but rather to a wide number of publications; each paper received a mean of 8 citations. The Iberian limnological research involved up to 5460 researchers, with a mean of 4.3 authors per paper. The research largely focused on fluvial systems, with 47 % of total publications (2778) devoted to these ecosystems. There was a dominant focus on local, within-system aspects of study sites and the research was mostly restricted to the Iberian Peninsula; larger spatial scales of analysis (i.e., landscape, regional, or global) tended to be overlooked. Iberian research addressed fundamental (75 %) rather than applied (17 %) or methodological (5 %) questions and was vastly dominated by observational approaches (75 %). Interestingly, Iberian limnological research increased its scientific productivity during the analysed decade at a higher rate than its international counterpart (increase of 119 %). Overall, Iberian research on limnology appeared to be in good health during the analysed decade. Certain areas have been more studied than others, which opens opportunities to develop new research.

Health-related quality of life in the Cambridge City over-75s Cohort (CC75C): development of a dementia-specific scale and descriptive analyses.

BACKGROUND: The assessment of Health Related Quality of Life (HRQL) is important in people with dementia as it could influence their care and support plan. Many studies on dementia do not specifically set out to measure dementia-specific HRQL but do include related items. The aim of this study is to explore the distribution of HRQL by functional and socio-demographic variables in a population-based setting. METHODS: Domains of DEMQOL's conceptual framework were mapped in the Cambridge City over 75's Cohort (CC75C) Study. HRQL was estimated in 110 participants aged 80+ years with a confirmed diagnosis of dementia with mild/moderate severity. Acceptability (missing values and normality of the total score), internal consistency (Cronbach's alpha), convergent, discriminant and known group differences validity (Spearman correlations, Wilcoxon Mann-Whitney and Kruskal-Wallis tests) were assessed. The distribution of HRQL by socio-demographic and functional descriptors was explored. RESULTS: The HRQL score ranged from 0 to 16 and showed an internal consistency Alpha of 0.74. Validity of the instrument was found to be acceptable. Men had higher HRQL than women. Marital status had a greater effect on HRQL for men than it did for women. The HRQL of those with good self-reported health was higher than those with fair/poor self-reported health. HRQL was not associated with dementia severity. CONCLUSIONS: To our knowledge this is the first study to examine the distribution of dementia-specific HRQL in a population sample of the very old. We have mapped an existing conceptual framework of dementia specific HRQL onto an existing study and demonstrated the feasibility of this approach. Findings in this study suggest that whereas there is big emphasis in dementia severity, characteristics such as gender should be taken into account when assessing and implementing programmes to improve HRQL.

Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

BACKGROUND: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD) in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. METHODS: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. RESULTS: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001), a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16), more previous MDD episodes (OR 0.92, P=0.007), previous treatments/therapies for depression (OR 0.78, P=0.030), and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001) were negatively associated with remission, whereas being male (OR 1.29, P=0.026) and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001) were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores and remission no longer appeared to be significant in this multiple regression (P=0.580), (P=0.008 in descriptive statistics), although it remained significant in a subgroup of patients treated with selective serotonin reuptake inhibitors (OR 0.97, P=0.023), but not in those treated with duloxetine (P=0.182). CONCLUSION: These findings are largely consistent with previous reports from the USA and Europe. They also highlight the potential mediating role of treatment with duloxetine on the negative relationship between depression-related pain and outcomes of depression.

On Value Creation at an Industrial Intersection – Bioenergy in the Forest and Energy Sectors

The traditional forest industry is a good example of the changing nature of the competitive environment in many industries. Faced with drastic challenges forestindustry companies are forced to search for new value-creating strategies in order to create competitive advantage. The emerging bioenergy business is now offering promising avenues for value creation for both the forest and energy sectors because of their complementary resources and knowledge with respect to bioenergy production from forest-based biomass. The key objective of this dissertation is to examine the sources of sustainable competitive advantage and the value-creation opportunities that are emerging at the intersection between the forest and energy industries. The research topic is considered from different perspectives in order to provide a comprehensive view of the phenomenon. The study discusses the business opportunities that are related to producing bioenergy from forest-based biomass, and sheds light on the greatest challenges and threats influencing the success of collaboration between the forest and energy sectors. In addition, it identifies existing and potential bioenergy actors, and considers the resources and capabilities needed in order to prosper in the bioenergy field. The value-creation perspective is founded on strategic management accounting, the theoretical frameworks are adopted from the field of strategic management, and the future aspect is taken into account through the application of futures studies research methodology. This thesis consists of two parts. The first part provides a synthesis of the overall dissertation, and the second part comprises four complementary research papers. There search setting is explorative in nature, and both qualitative and quantitative research methods are used. As a result, the thesis lays the foundation for non-technological studies on bioenergy. It gives an example of how to study new value-creation opportunities at an industrial intersection, and discusses the main determinants affecting the value-creation process. In order to accomplish these objectives the phenomenon of value creation at the intersection between the forest and energy industries is theorized and connected with the dynamic resource-based view of the firm.

El Papel de la motivación de los asesores y profesores en el proceso de asesoramiento = The figure of the motivation of the advisers and professors in the advice process

El escenario de asesoramiento colaborativo es un espacio sociocultural donde lo que se hace y se dice condiciona el tipo de interacción que se va a dar entre las personas que participan así como la actividad que llevan a cabo de manera conjunta. En este artículo vamos a reflexionar sobre el papel de la motivación de los profesores y asesores para mantener el asesoramiento así como en las posibilidades que tiene el asesor para crear y mantener un contexto que resulte motivante para asesor y asesorados

Optimization of solvent mixtures for extraction from bark of Schinus terebinthifolius by a statistical mixture-design technique and development of a UV-Vis spectrophotometric method for analysis of total polyphenols in the extract

A statistical mixture-design technique was used to study the effects of different solvents and their mixtures on the yield, total polyphenol content, and antioxidant capacity of the crude extracts from the bark of Schinus terebinthifolius Raddi (Anacardiaceae). The experimental results and their response-surface models showed that ternary mixtures with equal portions of all the three solvents (water, ethanol and acetone) were better than the binary mixtures in generating crude extracts with the highest yield (22.04 ± 0.48%), total polyphenol content (29.39 ± 0.39%), and antioxidant capacity (6.38 ± 0.21). An analytical method was developed and validated for the determination of total polyphenols in the extracts. Optimal conditions for the various parameters in this analytical method, namely, the time for the chromophoric reaction to stabilize, wavelength of the absorption maxima to be monitored, the reference standard and the concentration of sodium carbonate were determined to be 5 min, 780 nm, pyrogallol, and 14.06% w v-1, respectively. UV-Vis spectrophotometric monitoring of the reaction under these conditions proved the method to be linear, specific, precise, accurate, reproducible, robust, and easy to perform.

Managing regulatory risks when outsourcing network-related services in the electricity distribution sector

Deregulation of the electricity sector liberated the electricity sale and production for competitive forces while in the network business, electricity transmission and distribution, natural monopoly positions were recognised. Deregulation was accompanied by efficiencyoriented thinking on the whole electricity supply industry. For electricity distribution this meant a transition from a public service towards profit-driven business guided by economic regulation. Regulation is the primary means to enforce societal and other goals in the regulated monopoly sector. The design of economic regulation is concerned with two main attributes; end-customer price and quality of electricity distribution services. Regulation limits the costs of the regulated company but also defines the desired quality of monopoly services. The characteristics of the regulatory framework and the incentives it provides are therefore decisive for the electricity distribution sector. Regulation is not a static factor; changes in the regulatory practices cause discontinuity points, which in turn generate risks. A variety of social and environmental concerns together with technological advancements have emphasised the relevance of quality regulation, which is expected to lead to the large-scale replacement of overhead lines with underground cables. The electricity network construction activity is therefore currently witnessing revolutionary changes in its competitive landscape. In a business characterised by high statutory involvement and a high level of sunk costs, recognising and understanding the regulatory risks becomes a key success factor. As a response, electricity distribution companies have turned into outsourcing to attain efficiency and quality goals. This doctoral thesis addresses the impacts of regulatory risks on electricity network construction, which is a commonly outsourced activity in the electricity distribution network sector. The chosen research approach is characterised as an action analytical research on account of the fact that regulatory risks are greatly dependent on the individual nature of the regulatory regime applied in the electricity distribution sector. The main contribution of this doctoral thesis is to develop a concept for recognising and managing the business risks stemming from economic regulation. The degree of outsourcing in the sector is expected to increase in years to come. The results of the research provide new knowledge to manage the regulatory risks when outsourcing services.

BUDDHISM AND MODERNITY: IN THE MARGIN OF DONALD S. LOPEZ JR.'S "BUDDHISM AND SCIENCE

ABSTRACT The present article aims at setting the issue of the relationship between Buddhism and science in a historical and philosophical frame wider than that one taken into account by the international scholarship so far. The historical point of view allows us to conclude that the narrative that connects Buddhism with science is not based on features intrinsic to Buddhist thought. In fact, such narrative prospered thanks to the development of a dialectic, typical of the 18th and 19th centuries, between science and religion. The philosophical point of view allows us to conclude that such narrative is backed by a metaphysical-like thought that denies the specificity of both science and Buddhism.