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This document describes a mathematical model for energy system infrastructure planning problems. Its aim is to identify the most socioeconomically desirable energy system configuration for a given problem described within a MILP optimisation framework. The best configuration is identified in a way consistent with net present value calculations for a set of investments and operational needs. The energy system is complemented or created from scratch by the investments, enabling or providing alternative ways for the operational needs to be met. These are expressed as flow requirements in a set of networks that partly describe the energy system. Meeting them may require flows in and out of the system, potentially resulting in expenditures and revenue, in accordance with the respective tariffs. Internal flow distribution proceeds along pre-existing paths or those created through new investments, and is otherwise free, though not necessarily lossless. Losses are path segment-specific, depend on the solution deployed to allow flow along it, and can have static and flow-proportional components. Flows within the system have to be in equilibrium with another and compensate for losses and operational needs. The latter can also be dynamic if specified through modular sets of difference equations and constraints that can also be used to model interactions between networks. These structures are here termed flow converters and can also be introduced through investments. The formulation proposed also includes novelties, namely the structures necessary to use special ordered sets for selecting investments in paths, an alternative way to model static losses without intermediate nodes, and the possibility to define investments in groups of arcs rather than only on individual ones. Other key assumptions include the inexistence of flow delays and the precedence of investments relative to the planning period. Beyond these assumptions, the model design prioritised versatility and organisa

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with other neurodegenerative diseases (NDDs) linked to alpha-synuclein aggregation, also called synucleinopathies. Therefore, there is an urgent need to discover and validate early diagnostic and prognostic markers that reflect disease pathophysiology, progression, severity, and potential differences in disease mechanisms between PD and other NDDs. The close association between alpha-synuclein (aSyn) and the development of pathology in synucleinopathies, along with the identification of aSyn species in biological fluids, has led to increasing interest in aSyn species as potential biomarkers to detect PD and differentiate it from other synucleinopathies. In this review, we 1) provide an overview of the progress toward mapping the distribution of aSyn species in the brain, peripheral tissues, and biological fluids; 2) present comparative and critical analysis of previous studies to measure total aSyn as well as specific forms of monomeric, modified and aggregated forms of aSyn in different biological fluids; and 3) highlight conceptual and technical gaps and challenges that could hinder the development and validation of reliable aSyn biomarkers and outline a series of recommendations to address these challenges. Finally, we propose a combined biomarker approach based on integrating total aSyn levels with specific biomarkers based on the biochemical features (posttranslational modifications), aggregation and structure of aSyn, in addition to other biomarkers of neurodegeneration. We believe that capturing the diversity of aSyn species is essential to developing robust assays and diagnostics for early detection, patient stratification, monitoring of disease progression, and differentiation between synucleinopathy subtypes.

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with other neurodegenerative diseases (NDDs) linked to alpha-synuclein aggregation, also called synucleinopathies. Therefore, there is an urgent need to discover and validate early diagnostic and prognostic markers that reflect disease pathophysiology, progression, severity, and potential differences in disease mechanisms between PD and other NDDs. The close association between alpha-synuclein (aSyn) and the development of pathology in synucleinopathies, along with the identification of aSyn species in biological fluids, has led to increasing interest in aSyn species as potential biomarkers to detect PD and differentiate it from other synucleinopathies. In this review, we 1) provide an overview of the progress toward mapping the distribution of aSyn species in the brain, peripheral tissues, and biological fluids; 2) present comparative and critical analysis of previous studies to measure total aSyn as well as specific forms of monomeric, modified and aggregated forms of aSyn in different biological fluids; and 3) highlight conceptual and technical gaps and challenges that could hinder the development and validation of reliable aSyn biomarkers and outline a series of recommendations to address these challenges. Finally, we propose a combined biomarker approach based on integrating total aSyn levels with specific biomarkers based on the biochemical features (posttranslational modifications), aggregation and structure of aSyn, in addition to other biomarkers of neurodegeneration. We believe that capturing the diversity of aSyn species is essential to developing robust assays and diagnostics for early detection, patient stratification, monitoring of disease progression, and differentiation between synucleinopathy subtypes.

Background: Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. Methods: Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT-Protect 1 and 2, respectively. End points were two-step (RET2) and three-step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT-Protect 1. The identified peptides were then validated cross-sectionally in the remaining 1/3 from DIRECT-Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT-Protect 1 and 2 cohorts and significant peptides were tested longitudinally. Results: Follow-up ranged 4.0–4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: −.223, p < 0.001 and Rho: −.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. Conclusions: We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

Molecular studies of the proteome and metabolome in readily available body fluids such as urine and blood performed in a comprehensive qualitative and quantitative way are a valuable source of information for kidney disease research. They provide potential biomarkers of disease progression, markers of efficacy of interventions, as well as information on the underlying pathophysiology. Identified proteins and metabolites may point to dysregulated biological pathways and this knowledge may be useful in the identification of new treatment targets.Many studies, focusing on chronic kidney disease as well as diabetic nephropathy, demonstrate that peptidome and metabolome analysis can substantially contribute to early detection and prediction of disease progression, but also stratification of kidney disease in clinical practice. An innovative, well-explored application of urinary peptidome analysis is the back-translation of results obtained in humans to animals, for animal model validation and improvement of the preclinical readouts. In this chapter, we provide an overview of urinary proteomic analysis with the CE-MS analytical platform, a strategy that has been successfully employed in several studies for the identification and validation of biomarkers in kidney diseases. We describe how to obtain the orthology between the animal model and humans. We also deliver an overview of the analysis of the metabolome with the GC×GC-TOF-MS and UHPLC-Q-TOF-MS analytical platforms for blood and serum as new methods being applied in kidney disease.It is expected that a systems medicine approach to kidney disease including multiple omics methods will provide us with the best way to understand and treat diabetic kidney disease in the future.

Introduction: In Brazil, violence, regardless of the type, is the leading cause of death in adolescents and young adults.Objective: To describe the characteristics of the homicides in which female children and adolescents were the victims based on the autopsy reports recorded in the morgue of the city of Porto Alegre, Brazil.Materials and methods: Cross-sectional study in which 70 autopsy reports of girls and female adolescents who were killed between January 2010 and December 2016 were analyzed. The cases were evaluated according to the homicide motive or the homicide perpetrator, and five categories were established: drug trafficking related death, femicide, homicide perpetrated by a family member, death preceded by sexual violence, and death related to other transgressions.Results: There was a significant increase in the number of girls and female adolescents who were murdered between 2010 (n=7) and 2016 (n=19). Most of the homicides (64.2%) were related to drug, while femicide occurred in 15.7% of the cases. Homicides perpetrated by a family member, or preceded by sexual violence or related with other transgressions were less frequent as they occurred in 10%, 5.7% and 4.2% of the cases, respectively.Conclusion: Greater attention must be paid to the increase in the number of drug trafficking related homicides among female adolescents when creating and implementing relevant public policies., Introducción. En Brasil, la violencia, en sus diferentes manifestaciones, es la primera causa de muerte entre adolescentes y adultos jóvenes de ambos sexos.Objetivo. Describir las características de los homicidios de niñas y adolescentes registrados en la morgue de Porto Alegre, Brasil.Materiales y métodos. Estudio transversal que analizó 70 pericias de necropsia de jóvenes víctimas de homicidio entre enero de 2010 y diciembre de 2016. Los casos fueron evaluados según los motivos de los crímenes, identificando 5 categorías: muertes causadas por tráfico de drogas, feminicidios, homicidios familiares, muertes por violencia sexual y homicidios relacionados con otras infracciones legales.Resultados. Hubo un aumento significativo en el número de niñas y mujeres adolescentes víctimas de homicidio entre 2010 (n=7) y 2016 (n=19). La mayoría de casos estuvieron relacionados con el tráfico de estupefacientes (64.2%), mientras que los casos de feminicidio representaron 15.7% da la muestra. Los homicidios cometidos por un familiar, los precedidos de violencia sexual y aquellos relacionados con otras actividades ilegales fueron menos frecuentes con un 10%, 5.7% y 4.2%, respectivamente.Conclusiones. Es necesario prestar más atención al aumento de los homicidios en esta población relacionados con el tráfico de estupefacientes a la hora de crear e implementar políticas públicas al respecto.

Introduction: In Brazil, violence, regardless of the type, is the leading cause of death in adolescents and young adults.Objective: To describe the characteristics of the homicides in which female children and adolescents were the victims based on the autopsy reports recorded in the morgue of the city of Porto Alegre, Brazil.Materials and methods: Cross-sectional study in which 70 autopsy reports of girls and female adolescents who were killed between January 2010 and December 2016 were analyzed. The cases were evaluated according to the homicide motive or the homicide perpetrator, and five categories were established: drug trafficking related death, femicide, homicide perpetrated by a family member, death preceded by sexual violence, and death related to other transgressions.Results: There was a significant increase in the number of girls and female adolescents who were murdered between 2010 (n=7) and 2016 (n=19). Most of the homicides (64.2%) were related to drug, while femicide occurred in 15.7% of the cases. Homicides perpetrated by a family member, or preceded by sexual violence or related with other transgressions were less frequent as they occurred in 10%, 5.7% and 4.2% of the cases, respectively.Conclusion: Greater attention must be paid to the increase in the number of drug trafficking related homicides among female adolescents when creating and implementing relevant public policies., Introducción. En Brasil, la violencia, en sus diferentes manifestaciones, es la primera causa de muerte entre adolescentes y adultos jóvenes de ambos sexos.Objetivo. Describir las características de los homicidios de niñas y adolescentes registrados en la morgue de Porto Alegre, Brasil.Materiales y métodos. Estudio transversal que analizó 70 pericias de necropsia de jóvenes víctimas de homicidio entre enero de 2010 y diciembre de 2016. Los casos fueron evaluados según los motivos de los crímenes, identificando 5 categorías: muertes causadas por tráfico de drogas, feminicidios, homicidios familiares, muertes por violencia sexual y homicidios relacionados con otras infracciones legales.Resultados. Hubo un aumento significativo en el número de niñas y mujeres adolescentes víctimas de homicidio entre 2010 (n=7) y 2016 (n=19). La mayoría de casos estuvieron relacionados con el tráfico de estupefacientes (64.2%), mientras que los casos de feminicidio representaron 15.7% da la muestra. Los homicidios cometidos por un familiar, los precedidos de violencia sexual y aquellos relacionados con otras actividades ilegales fueron menos frecuentes con un 10%, 5.7% y 4.2%, respectivamente.Conclusiones. Es necesario prestar más atención al aumento de los homicidios en esta población relacionados con el tráfico de estupefacientes a la hora de crear e implementar políticas públicas al respecto.

For the very first time in EU history, the 2014 EP elections provided citizens with the opportunity to influence the nomination of the Commission President by casting a vote for the main Europarties’ ‘lead candidates’. By subjecting the position of the Commission President to an open political contest, many experts have formulated the expectation that heightened political competition would strengthen the weak electoral connection between EU citizens and EU legislators, which some consider a root cause for the EU’s lack of public support. In particular, this contest was on display in the so-called ‘Eurovision Debate’, a televised debate between the main contenders for the Commission President broadcasted live across Europe. Drawing on a quasi-experimental study conducted in 24 EU countries, we find that debate exposure led to increased cognitive and political involvement and EU support among young citizens. Unfortunately, the debate has only reached a very small audience.

For the very first time in EU history, the 2014 EP elections provided citizens with the opportunity to influence the nomination of the Commission President by casting a vote for the main Europarties’ ‘lead candidates’. By subjecting the position of the Commission President to an open political contest, many experts have formulated the expectation that heightened political competition would strengthen the weak electoral connection between EU citizens and EU legislators, which some consider a root cause for the EU’s lack of public support. In particular, this contest was on display in the so-called ‘Eurovision Debate’, a televised debate between the main contenders for the Commission President broadcasted live across Europe. Drawing on a quasi-experimental study conducted in 24 EU countries, we find that debate exposure led to increased cognitive and political involvement and EU support among young citizens. Unfortunately, the debate has only reached a very small audience.

Political parties increasingly rely on self-regulation to promote ethical standards in office. The adoption of ethics self-regulation and its ability to induce change is likely to be a function of the responses from politicians and voters. Without external enforcement mechanisms, compliance requires support from legislators. In turn, if voters perceive self-regulation as cheap talk, officials have fewer incentives to acquiesce. The extent to which such efforts are rewarded by voters and supported by elected officials remains an open question. We examine this question in a paired conjoint experiment with elected officials and voters in Portugal and Spain. The results show that politicians support (and voters reward) financial disclosures, lobbying registries, and sanctions for MPs involved in corruption cases. Voters also reward term limits, and the effects are not moderated by ideological agreement. The findings suggest that parties can benefit from promoting transparency reforms and are not penalized by experimentation.

How do people respond to different decision-making processes in high courts? One long-standing view suggests that citizens expect courts to be neutral arbiters of legal controversies. Although the relevance of such “myth of legality” has been challenged, we know very little about the relationship between the portrayals of the motives of courts and justices and public attitudes in civil law countries. We explore this question in a pair of experiments in Norway and Portugal where we isolate the effects of different institutional frames from outcome favorability. We find that while partisan frames are detrimental to fairness perceptions and acceptance of decisions, depictions of judicial decision-making that emphasize policy goals do not adversely affect citizens’ responses in comparison with legalistic frames. The results suggest that, even in civil law systems, preserving the myth of legality may not be a necessary condition to elicit public support for judicial decisions.

Most Europeans value democracy, but do all citizens have the same conception of what democracy is? Pedro C. Magalhães and Besir Ceka assess variations in how Europeans conceive of democracy and analyse the various factors which underpin different interpretations. Their findings indicate that there are a wide variety of conceptions of democracy across Europe. The key mechanism explaining this variation is that individuals in high education and high income groups tend to more readily support the kinds of democracy which represent the ‘status quo’ in their country than citizens from lower education/income groups.

This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multisite study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n = 130) or intensive psychotherapy (IP; n = 163), with study-based pharmacotherapy. Participants (N = 243) were defined as current (past week) short sleepers (<6 hours/night), normal sleepers (6.5-8.5 hours/night), and long sleepers (≥9 hours/night), according to reported average nightly sleep duration the week before randomization. Sleep disturbances did not predict the likelihood of recovery nor time until recovery from a depressive episode. There was no difference in recovery rates between IP versus CC for normal sleepers, and medium effect sizes were observed for differences in short and long sleepers. In this study, sleep did not play a major role in predicting or moderating response to psychotherapy in bipolar disorder.

In this article we analyze the evolution of the attitudes towards Europe of Portuguese parliamentary elites in the context of the sovereign debt crisis. Our analysis relies on interviews to a total of 227 MPs in the context of the ENEC project in 2014 and of the Intune Project in 2009 and 2007. Our principal finding is that an important gap has risen between the attitudes of the MPs and of the masses. Indeed, while the Portuguese are becoming increasingly less pro-European, this is not the case of their deputies. We show that, in 2014, the percentage of deputies that believed that EU membership benefited the country has decreased a little, but it stays as high as 89%. Our data, however, show that MPs now exhibit lower levels of trust towards the European institutions. Interestingly, the drop in the levels of trust towards EU institutions does not affect all institutions equally: trust towards the European Parliament remains constant regarding 2007, whereas the levels of trust in the remaining two institutions decrease. Finally, we show that it is in the Socialist Party (PS) that there is the steepest decline in the level of overall trust, which is rooted in declining levels of confidence in the European Commission. Given that PS has traditionally portrayed itself as the most pro-Europe of the Portuguese parties, this is solid evidence of a growing discontent with the European Commission.

BACKGROUND: Little is known about predictors of recovery from bipolar depression. AIMS: We investigated affective instability (a pattern of frequent and large mood shifts over time) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychosocial treatment for acute depression. METHOD: A total of 252 out-patients with DSM-IV bipolar I or II disorder and who were depressed enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and were randomised to one of three types of intensive psychotherapy for depression (n = 141) or a brief psychoeducational intervention (n = 111). All analyses were by intention-to-treat. RESULTS: Degree of instability of symptoms of depression and mania predicted a lower likelihood of recovery and longer time until recovery, independent of the concurrent effects of symptom severity. Affective instability did not moderate the effects of psychosocial treatment on recovery from depression. CONCLUSIONS: Affective instability may be a clinically relevant characteristic that influences the course of bipolar depression.

Escherichia coli is a commensal microorganism of the gastrointestinal tract of animals and humans and it is an excellent model organism for the study of antibiotic resistance mechanisms. The resistance transmission and other characteristics of bacteria are based on different types of gene transfer occurring throughout the bacterial evolution. One of which is horizontal gene transfer that allows us to understand the ability of bacteria to acquire new genes. One dimensional and two dimensional electrophoresis (2-DE) techniques were performed in order to identify and characterize the proteome of two E. coli strains: Electromax DH10B, a transformation-ready strain; and TF-Se20, the Electromax DH10B that contains the aac(6′)-Ib-cr4-harboring pMdT1 plasmid. After 2-DE and subsequent analysis by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), it was possible to identify 76 distinct proteins on the TF-Se20 strain, whereas 71 had a known function. From Electromax DH10B strain, 72 different proteins were identified of which 71 were associated with a biological process. The protein of interest, aminoglycoside N-(6′)-acetyltransferase type 1, was identified by MALDI-TOF MS. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was performed to determine its sequence. Seventy six percent of the acetylase sequence was reconstructed only in the TF-Se20 strain, representing the single protein associated to antibiotic resistance. MALDI-TOF MS and LC-MS/MS approaches allowed us to determine the total proteome of both strains, as well as the acetylase sequence. Both of them enhance the ability to obtain more accurate information about the mechanisms of antimicrobial resistance. The pMdT1 plasmid brings a new perspective in understanding the metabolic processes that lead to antibiotic resistance. Biological significance This study highlights the importance of proteomics and bioinformatics in understanding mechanisms of gene

ObjectiveAt least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome.MethodIn the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three-session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year.ResultsA total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat=5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect).ConclusionsDepressed patients with bipo

In an attempt to understand the beneficial health effects of Artemisia annua other than its anti-malaria properties, extracts from different cultivars prepared as tea infusions were investigated using Caco-2 cells on the intestinal inflammation and cytochrome P450 (CYP) activities. The characterisation of their phenolic compound (PC) profile revealed rosmarinic and chlorogenic acids as the main PCs. The extracts, assayed on Caco-2 cells at a plausible intestinal concentration, significantly decreased the secretion of pro-inflammatory cytokines, IL-8 and IL-6. This effect could be attributable at least to their content in rosmarinic acid, detected as a potent anti-inflammatory compound. The extracts also inhibited the activity of CYP3A4, whose expression was induced by 1,25-dihydroxyvitamin D3, and of CYP1A1, induced by benzo(a)pyrene. Our results highlight the advantage of drinking A. annua infusions for their potent anti-inflammatory effect, linked to PC content, which could synergise their antimalarial activity.

Although a large body of research has been produced both on semi-presidential regimes and patterns of electoral change from general elections to midterm or other non-general elections, the study of presidential elections in semi-presidential regimes remains, to quote one of the few exceptions in this regard, “uncharted territory” in the political science literature. Using a dataset on election results and turnout levels in all semi-presidential democracies since 1945, we test several hypotheses about changes in turnout levels and government parties and coalitions’ gains and losses in presidential elections. We show that while semi-presidential democracies with weaker presidencies do approximate the patterns predicted by the “second-order” model, that is clearly not the case where presidents hold more considerable powers, where government losses are explained by “negative voting” and “balancing” theories. The implications of these findings for the very definition of “semi-presidentialism” and the consequences of these regimes are also discussed.