TMS- EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

A technological framework based on automatic messaging for improving adherence of diabetic patients

En todo el mundo se ha observado un crecimiento exponencial en la incidencia de enfermedades crónicas como la hipertensión y enfermedades cardiovasculares y respiratorias, así como la diabetes mellitus, que causa un número de muertes cada vez mayor en todo el mundo (Beaglehole et al., 2008). En concreto, la prevalencia de diabetes mellitus (DM) está aumentando de manera considerable en todas las edades y representa un serio problema de salud mundial. La diabetes fue la responsable directa de 1,5 millones de muertes en 2012 y 89 millones de años de vida ajustados por discapacidad (AVAD) (OMS, 2014). Uno de los principales dilemas que suelen asociarse a la gestión de EC es la adherencia de los pacientes a los tratamientos, que representa un aspecto multifactorial que necesita asistencia en lo relativo a: educación, autogestión, interacción entre los pacientes y cuidadores y compromiso de los pacientes. Medir la adherencia del tratamiento es complicado y, aunque se ha hablado ampliamente de ello, aún no hay soluciones “de oro” (Reviews, 2002). El compromiso de los pacientes, a través de la participación, colaboración, negociación y a veces del compromiso firme, aumentan las oportunidades para una terapia óptima en la que los pacientes se responsabilizan de su parte en la ecuación de adherencia. Comprometer e involucrar a los pacientes diabéticos en las decisiones de su tratamiento, junto con expertos profesionales, puede ayudar a favorecer un enfoque centrado en el paciente hacia la atención a la diabetes (Martin et al., 2005). La motivación y atribución de poder de los pacientes son quizás los dos factores interventores más relevantes que afectan directamente a la autogestión de la atención a la diabetes. Se ha demostrado que estos dos factores desempeñan un papel fundamental en la adherencia a la prescripción, así como en el fomento exitoso de un estilo de vida sana y otros cambios de conducta (Heneghan et al., 2013). Un plan de educación personalizada es indispensable para proporcionarle al paciente las herramientas adecuadas que necesita para la autogestión efectiva de la enfermedad (El-Gayar et al. 2013). La comunicación efectiva es fundamental para proporcionar una atención centrada en el paciente puesto que influye en las conductas y actitudes hacia un problema de salud ((Frampton et al. 2008). En este sentido, la interactividad, la frecuencia, la temporalización y la adaptación de los mensajes de texto pueden promover la adherencia a un régimen de medicación. Como consecuencia, adaptar los mensajes de texto a los pacientes puede resultar ser una manera de hacer que las sugerencias y la información sean más relevantes y efectivas (Nundy et al. 2013). En este contexto, las tecnologías móviles en el ámbito de la salud (mHealth) están desempeñando un papel importante al conectar con pacientes para mejorar la adherencia a medicamentos recetados (Krishna et al., 2009). La adaptación de los mensajes de texto específicos de diabetes sigue siendo un área de oportunidad para mejorar la adherencia a la medicación y ofrecer motivación a adultos con diabetes. Sin embargo, se necesita más investigación para entender totalmente su eficacia. Los consejos de texto personalizados han demostrado causar un impacto positivo en la atribución de poder a los pacientes, su autogestión y su adherencia a la prescripción (Gatwood et al., 2014). mHealth se puede utilizar para ofrecer programas de asistencia de autogestión a los pacientes con diabetes y, al mismo tiempo, superar las dificultades técnicas y financieras que supone el tratamiento de la diabetes (Free at al., 2013). El objetivo principal de este trabajo de investigación es demostrar que un marco tecnológico basado en las teorías de cambios de conducta, aplicado al campo de la mHealth, permite una mejora de la adherencia al tratamiento en pacientes diabéticos. Como método de definición de una solución tecnológica, se han adoptado un conjunto de diferentes técnicas de conducta validadas denominado marco de compromiso de retroacción conductual (EBF, por sus siglas en inglés) para formular los mensajes, guiar el contenido y evaluar los resultados. Los estudios incorporan elementos del modelo transteórico (TTM, por sus siglas en inglés), la teoría de la fijación de objetivos (GST, por sus siglas en inglés) y los principios de comunicación sanitaria persuasiva y eficaz. Como concepto general, el modelo TTM ayuda a los pacientes a progresar a su próxima fase de conducta a través de mensajes de texto motivados específicos y permite que el médico identifique la fase actual y adapte sus estrategias individualmente. Además, se adoptan las directrices del TTM para fijar objetivos personalizados a un nivel apropiado a la fase de cambio del paciente. La GST encierra normas que van a ponerse en práctica para promover la intervención educativa y objetivos de pérdida de peso. Finalmente, los principios de comunicación sanitaria persuasiva y eficaz aplicados a la aparición de los mensajes se han puesto en marcha para aumentar la efectividad. El EBF tiene como objetivo ayudar a los pacientes a mejorar su adherencia a la prescripción y encaminarlos a una mejora general en la autogestión de la diabetes mediante mensajes de texto personalizados denominados mensajes de retroacción automáticos (AFM, por sus siglas en inglés). Después de una primera revisión del perfil, consistente en identificar características significativas del paciente basadas en las necesidades de tratamiento, actitudes y conductas de atención sanitaria, el sistema elige los AFM personalizados, los aprueba el médico y al final se transfieren a la interfaz del paciente. Durante el tratamiento, el usuario recopila los datos en dispositivos de monitorización de pacientes (PMD, por sus siglas en inglés) de una serie de dispositivos médicos y registros manuales. Los registros consisten en la toma de medicación, dieta y actividad física y tareas de aprendizaje y control de la medida del metabolismo. El compromiso general del paciente se comprueba al estimar el uso del sistema y la adherencia del tratamiento y el estado de los objetivos del paciente a corto y largo plazo. El módulo de análisis conductual, que consiste en una serie de reglas y ecuaciones, calcula la conducta del paciente. Tras lograr el análisis conductual, el módulo de gestión de AFM actualiza la lista de AFM y la configuración de los envíos. Las actualizaciones incluyen el número, el tipo y la frecuencia de mensajes. Los AFM los revisa periódicamente el médico que también participa en el perfeccionamiento del tratamiento, adaptado a la fase transteórica actual. Los AFM se segmentan en distintas categorías y niveles y los pacientes pueden ajustar la entrega del mensaje de acuerdo con sus necesidades personales. El EBF se ha puesto en marcha integrado dentro del sistema METABO, diseñado para facilitar al paciente diabético que controle sus condiciones relevantes de una manera menos intrusiva. El dispositivo del paciente se vincula en una plataforma móvil, mientras que una interfaz de panel médico permite que los profesionales controlen la evolución del tratamiento. Herramientas específicas posibilitan que los profesionales comprueben la adherencia del paciente y actualicen la gestión de envíos de AFM. El EBF fue probado en un proyecto piloto controlado de manera aleatoria. El principal objetivo era examinar la viabilidad y aceptación del sistema. Los objetivos secundarios eran también la evaluación de la eficacia del sistema en lo referente a la mejora de la adherencia, el control glucémico y la calidad de vida. Se reclutaron participantes de cuatro centros clínicos distintos en Europa. La evaluación del punto de referencia incluía datos demográficos, estado de la diabetes, información del perfil, conocimiento de la diabetes en general, uso de las plataformas TIC, opinión y experiencia con dispositivos electrónicos y adopción de buenas prácticas con la diabetes. La aceptación y eficacia de los criterios de evaluación se aplicaron para valorar el funcionamiento del marco tecnológico. El principal objetivo era la valoración de la eficacia del sistema en lo referente a la mejora de la adherencia. En las pruebas participaron 54 pacientes. 26 fueron asignados al grupo de intervención y equipados con tecnología móvil donde estaba instalado el EBF: 14 pacientes tenían T1DM y 12 tenían T2DM. El grupo de control estaba compuesto por 25 pa cientes que fueron tratados con atención estándar, sin el empleo del EBF. La intervención profesional tanto de los grupos de control como de intervención corrió a cargo de 24 cuidadores, entre los que incluían diabetólogos, nutricionistas y enfermeras. Para evaluar la aceptabilidad del sistema y analizar la satisfacción de los usuarios, a través de LimeSurvey, se creó una encuesta multilingüe tanto para los pacientes como para los profesionales. Los resultados también se recopilaron de los archivos de registro generados en los PMD, el panel médico profesional y las entradas de la base de datos. Los mensajes enviados hacia y desde el EBF y los archivos de registro del sistema y los servicios de comunicación se grabaron durante las cinco semanas del estudio. Se entregaron un total de 2795 mensajes, lo que supuso una media de 107,50 mensajes por paciente. Como se muestra, los mensajes disminuyen con el tiempo, indicando una mejora global de la adherencia al plan de tratamiento. Como se esperaba, los pacientes con T1DM recibieron más consejos a corto plazo, en relación a su estado. Del mismo modo, al ser el centro de T2DM en cambios de estilo de vida sostenible a largo plazo, los pacientes con T2DM recibieron más consejos de recomendación, en cuanto a dietas y actividad física. También se ha llevado a cabo una comparación de la adherencia e índices de uso para pacientes con T1DM y T2DM, entre la primera y la segunda mitad de la prueba. Se han observado resultados favorables para el uso. En lo relativo a la adherencia, los resultados denotaron una mejora general en cada dimensión del plan de tratamiento, como la nutrición y las mediciones de inserción de glucosa en la sangre. Se han llevado a cabo más estudios acerca del cambio a nivel educativo antes y después de la prueba, medidos tanto para grupos de control como de intervención. Los resultados indicaron que el grupo de intervención había mejorado su nivel de conocimientos mientras que el grupo de control mostró una leve disminución. El análisis de correlación entre el nivel de adherencia y las AFM ha mostrado una mejora en la adherencia de uso para los pacientes que recibieron los mensajes de tipo alertas, y unos resultados no significativos aunque positivos relacionados con la adherencia tanto al tratamiento que al uso correlacionado con los recordatorios. Por otra parte, los AFM parecían ayudar a los pacientes que no tomaban suficientemente en serio su tratamiento en el principio y que sí estaban dispuestos a responder a los mensajes recibidos. Aun así, los pacientes que recibieron demasiadas advertencias, comenzaron a considerar el envío de mensajes un poco estresante. El trabajo de investigación llevado a cabo al desarrollar este proyecto ofrece respuestas a las cuatro hipótesis de investigación que fueron la motivación para el trabajo. • Hipótesis 1 : es posible definir una serie de criterios para medir la adherencia en pacientes diabéticos. • Hipótesis 2: es posible diseñar un marco tecnológico basado en los criterios y teorías de cambio de conducta mencionados con anterioridad para hacer que los pacientes diabéticos se comprometan a controlar su enfermedad y adherirse a planes de atención. • Hipótesis 3: es posible poner en marcha el marco tecnológico en el sector de la salud móvil. • Hipótesis 4: es posible utilizar el marco tecnológico como solución de salud móvil en un contexto real y tener efectos positivos en lo referente a indicadores de control de diabetes. La verificación de cada hipótesis permite ofrecer respuesta a la hipótesis principal: La hipótesis principal es: es posible mejorar la adherencia diabética a través de un marco tecnológico mHealth basado en teorías de cambio de conducta. El trabajo llevado a cabo para responder estas preguntas se explica en este trabajo de investigación. El marco fue desarrollado y puesto en práctica en el Proyecto METABO. METABO es un Proyecto I+D, cofinanciado por la Comisión Europea (METABO 2008) que integra infraestructura móvil para ayudar al control, gestión y tratamiento de los pacientes con diabetes mellitus de tipo 1 (T1DM) y los que padecen diabetes mellitus de tipo 2 (T2DM). ABSTRACT Worldwide there is an exponential growth in the incidence of Chronic Diseases (CDs), such as: hypertension, cardiovascular and respiratory diseases, as well as diabetes mellitus, leading to rising numbers of deaths worldwide (Beaglehole et al. 2008). In particular, the prevalence of diabetes mellitus (DM) is largely increasing among all ages and constitutes a major worldwide health problem. Diabetes was directly responsible for 1,5 million deaths in 2012 and 89 million Disability-adjusted life year (DALYs) (WHO 2014). One of the key dilemmas often associated to CD management is the patients’ adherence to treatments, representing a multi-factorial aspect that requires support in terms of: education, self-management, interaction between patients and caregivers, and patients’ engagement. Measuring adherence is complex and, even if widely discussed, there are still no “gold” standards ((Giardini et al. 2015), (Costa et al. 2015). Patient’s engagement, through participation, collaboration, negotiation, and sometimes compromise, enhance opportunities for optimal therapy in which patients take responsibility for their part of the adherence equation. Engaging and involving diabetic patients in treatment decisions, along with professional expertise, can help foster a patient-centered approach to diabetes care (Martin et al. 2005). Patients’ motivation and empowerment are perhaps the two most relevant intervening factors that directly affect self-management of diabetes care. It has been demonstrated that these two factors play an essential role in prescription adherence, as well as for the successful encouragement of a healthy life-style and other behavioural changes (Heneghan et al. 2013). A personalised education plan is indispensable in order to provide the patient with the appropriate tools needed for the effective self-management of the disease (El-Gayar et al. 2013). Effective communication is at the core of providing patient-centred care since it influences behaviours and attitudes towards a health problem (Frampton et al. 2008). In this regard, interactivity, frequency, timing, and tailoring of text messages may promote adherence to a medication regimen. As a consequence, tailoring text messages to patients can constitute a way of making suggestions and information more relevant and effective (Nundy et al. 2013). In this context, mobile health technologies (mHealth) are playing significant roles in improving adherence to prescribed medications (Krishna et al. 2009). The tailoring of diabetes-specific text messages remains an area of opportunity to improve medication adherence and provide motivation to adults with diabetes but further research is needed to fully understand their effectiveness. Personalized text advices have proven to produce a positive impact on patients’ empowerment, self-management, and adherence to prescriptions (Gatwood et al. 2014). mHealth can be used for offering self-management support programs to diabetes patients and at the same time surmounting the technical and financial difficulties involved in diabetes treatment (Free et al. 2013). The main objective of this research work is to demonstrate that a technological framework, based on behavioural change theories, applied to mHealth domain, allows improving adherence treatment in diabetic patients. The framework, named Engagement Behavioural Feedback Framework (EBF), is built on top of validated behavioural techniques to frame messages, guide the definition of contents and assess outcomes: elements from the Transtheoretical Model (TTM), the Goal-Setting Theory (GST), Effective Health Communication (EHC) guidelines and Principles of Persuasive Technology (PPT) were incorporated. The TTM helps patients to progress to a next behavioural stage, through specific motivated text messages, and allow clinician’s identifying the current stage and tailor its strategies individually. Moreover, TTM guidelines are adopted to set customised goals at a level appropriate to the patient’s stage of change. The GST was used to build rules to be applied for enhancing educational intervention and weight loss objectives. Finally, the EHC guidelines and the PPT were applied to increase the effectiveness of messages. The EBF aims to support patients on improving their prescription adherence and persuade them towards a general improvement in diabetes self-management, by means of personalised text messages, named Automatic Feedback Messages (AFM). After a first profile screening, consisting in identifying meaningful patient characteristics based on treatment needs, attitudes and health care behaviours, customised AFMs are selected by the system, approved by the professional, and finally transferred into the patient interface. During the treatment, the user collects the data into a Patient Monitoring Device (PMD) from a set of medical devices and from manual inputs. Inputs consist in medication intake, diet and physical activity, metabolic measurement monitoring and learning tasks. Patient general engagement is checked by estimating the usage of the system and the adherence of treatment and patient goals status in the short and the long term period. The Behavioural Analysis Module, consisting in a set of rules and equations, calculates the patient’s behaviour. After behavioural analysis is accomplished, the AFM library and the dispatch setting are updated by the AFM Manager module. Updates include the number, the type and the frequency of messages. The AFMs are periodically supervised by the professional who also participates to the refinement of the treatment, adapted to the current transtheoretical stage. The AFMs are segmented in different categories and levels and patients can adjust message delivery in accordance with their personal needs. The EBF was integrated to the METABO system, designed to facilitate diabetic patients in managing their disease in a less intrusive approach. Patient device corresponds in a mobile platform, while a medical panel interface allows professionals to monitoring the treatment evolution. Specific tools allow professional to check patient adherence and to update the AFMs dispatch management. The EBF was tested in a randomised controlled pilot. The main objective was to examine the feasibility and acceptance of the system. Secondary objectives were also the assessment of the effectiveness of system in terms of adherence improvement, glycaemic control, and quality of life. Participants were recruited from four different clinical centres in Europe. The baseline assessment included demographics, diabetes status, profile information, knowledge about diabetes in general, usage of ICT platforms, opinion and experience about electronic devices and adoption of good practices with diabetes. Acceptance and the effectiveness evaluation criteria were applied to evaluate the performance of the technological framework. The main objective was the assessment of the effectiveness of system in terms of adherence improvement. Fifty-four patients participated on the trials. Twenty-six patients were assigned in the intervention group and equipped with mobile where the EBF was installed: 14 patients were T1DM and 12 were T2DM. The control group was composed of 25 patients that were treated through a standard care, without the usage of the EBF. Professional’s intervention for both intervention and control groups was carried out by 24 care providers, including endocrinologists, nutritionists, and nurses. In order to evaluate the system acceptability and analyse the users’ satisfaction, an online multi-language survey, using LimeSurvey, was produced for both patients and professionals. Results were also collected from the log-files generated in the PMDs, the professional medical panel and the entries of the data base. The messages sent to and from the EBF and the log-files of the system and communication services were recorded over 5 weeks of the study. A total of 2795 messages were submitted, representing an average of 107,50 messages per patient. As demonstrated, messages decrease over time indicating an overall improvement of the care plan’s adherence. As expected, T1DM patients were more loaded with short-term advices, in accordance with their condition. Similarly, being the focus of T2DM on long-term sustainable lifestyle changes, T2DM received more reminders advices, as for diet and physical activity. Favourable outcomes were observed for treatment and usage adherences of the intervention group: for both the adherence indices, results denoted a general improvement on each care plan’s dimension, such as on nutrition and blood glucose input measurements. Further studies were conducted on the change on educational level before and after the trial, measured for both control and intervention groups. The outcomes indicated the intervention group has improved its level of knowledge, while the control group denoted a low decrease. The correlation analysis between the level of adherences and the AFMs showed an improvement in usage adherence for patients who received warnings message, while non-significantly yet even positive indicators related to both treatment and usage adherence correlated with the Reminders. Moreover, the AFMs seemed to help those patients who did not take their treatment seriously enough in the beginning and who were willing to respond to the messages they received. Even though, patients who received too many Warnings, started to consider the message dispatch to be a bit stressful. The research work carried out in developing this research work provides responses to the four research hypothesis that were the motivation for the work: •Hypothesis 1: It is possible to define a set of criteria to measure adherence in diabetic patients. •Hypothesis 2: It is possible to design a technological framework, based on the aforementioned criteria and behavioural change theories, to engage diabetic patients in managing their disease and adhere to care plans. •Hypothesis 3: It is possible to implement the technological framework in the mobile health domain. •Hypothesis 4: It is possible to use the technological framework as a mobile health solution in a real context and have positive effects in terms of diabetes management indicators. The verification of each hypothesis allowed us to provide a response to the main hypothesis: The Main Hypothesis is: It is possible to improve diabetic adherence through a mHealth technological framework based on behavioural change theories. The work carried out to answer these questions is explained in this research work. The framework was developed and applied in the METABO project. METABO is an R&D project, co-funded by the European Commission (METABO 2008) that integrates mobile infrastructure for supporting the monitoring, management, and treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients.

Recurrent invasion and extinction of a selfish gene

Homing endonuclease genes show super-Mendelian inheritance, which allows them to spread in populations even when they are of no benefit to the host organism. To test the idea that regular horizontal transmission is necessary for the long-term persistence of these genes, we surveyed 20 species of yeasts for the ω-homing endonuclease gene and associated group I intron. The status of ω could be categorized into three states (functional, nonfunctional, or absent), and status was not clustered on the host phylogeny. Moreover, the phylogeny of ω differed significantly from that of the host, strong evidence of horizontal transmission. Further analyses indicate that horizontal transmission is more common than transposition, and that it occurs preferentially between closely related species. Parsimony analysis and coalescent theory suggest that there have been 15 horizontal transmission events in the ancestry of our yeast species, through simulations indicate that this value is probably an underestimate. Overall, the data support a cyclical model of invasion, degeneration, and loss, followed by reinvasion, and each of these transitions is estimated to occur about once every 2 million years. The data are thus consistent with the idea that frequent horizontal transmission is necessary for the long-term persistence of homing endonuclease genes, and further, that this requirement limits these genes to organisms with easily accessible germ lines. The data also show that mitochondrial DNA sequences are transferred intact between yeast species; if other genes do not show such high levels of horizontal transmission, it would be due to lack of selection, rather than lack of opportunity.

Adult fitness consequences of sexual selection in Drosophila melanogaster

Few experiments have demonstrated a genetic correlation between the process of sexual selection and fitness benefits in offspring, either through female choice or male competition. Those that have looked at the relationship between female choice and offspring fitness have focused on juvenile fitness components, rather than fitness at later stages in the life cycle. In addition, many of these studies have not controlled for possible maternal effects. To test for a relationship between sexual selection and adult fitness, we carried out an artificial selection experiment in the fruit fly, Drosophila melanogaster. We created two treatments that varied in the level of opportunity for sexual selection. Increased opportunity for female choice and male competition was genetically correlated with an increase in adult survivorship, as well as an increase in male and female body size. Contrary to previous, single-generation studies, we did not find an increase in larval competitive ability. This study demonstrates that mate choice and/or male–male competition are correlated with an increase in at least one adult fitness component of offspring.

Rates of nucleotide substitution in sexual and anciently asexual rotifers

The class Bdelloidea of the phylum Rotifera is the largest well studied eukaryotic taxon in which males and meiosis are unknown, and the only one for which these indications of ancient asexuality are supported by cytological and molecular genetic evidence. We estimated the rates of synonymous and nonsynonymous substitutions in the hsp82 heat shock gene in bdelloids and in facultatively sexual rotifers of the class Monogononta, employing distance based and maximum likelihood methods. Relative-rate tests, using acanthocephalan rotifers as an outgroup, showed slightly higher rates of nonsynonymous substitution and slightly lower rates of synonymous substitution in bdelloids as compared with monogononts. The opposite trend, however, was seen in intraclass pairwise comparisons. If, as it seems, bdelloids have evolved asexually, an equality of bdelloid and monogonont substitution rates would suggest that the maintenance of sexual reproduction in monogononts is not attributable to an effect of sexual reproduction in limiting the load of deleterious nucleotide substitutions.

Enhancing Conservation Options: An Argument for Statutory Recognition of Options to Purchase Conservation Easements (OPCEs)

The most dynamic component of the conservation movement in the United States for the past three decades has been land conservation transactions. In the United States, land conservation organizations have protected roughly 40 million acres of land through transactions. Most of these acres have been protected using conservation easements. Climate change threatens the vast conservation edifice created by land conservation transactions. The tools of land conservation transactions are, traditionally, stationary. Climate change means that the resources that land conservation transactions were intended to protect may no longer remain on the land protected. Options to purchase conservation easements (OPCEs) have long played a modest but important role in conservation law practice. In the world climate change is creating, with its substantial uncertainties and shifting windows of opportunity, OPCEs can serve more complicated and strategic purposes. The ability of OPCEs to serve important roles in protecting land in the context of uncertainty would be significantly increased if state legislatures amend current conservation easement statutes to (1) specifically recognize OPCEs, (2) immunize OPCEs from a range of potential common law challenges, (3) guarantee the durability and transferability of OPCEs, and (4) integrate OPCEs into the burgeoning body of conservation easement law. These statutory amendments would do for OPCEs what conservation easement statutes have done for conservation easements: transform them into an essential multi-purpose tool for conservation in a changing world.

Emergent Brazil and the Curse of the ‘Hen’s Flight’. CEPS Working Document No. 379, 27 February 2013

The ‘Emergent Brazil’ growth model is reaching its limits. Its main engines have been slowing significantly since the beginning of the global financial and economic crisis. Even its much-praised predictable macroeconomic policy has been eroded by political interference. Inflationary pressures are growing and GDP performance is anaemic. As ominous, Brazil cannot compensate for its domestic deficiencies with an export drive. Commodity exports are suffering with the world economic slow-down and the manufacturing industries’ competitiveness is in sharp decline. Brazil has put all its trade negotiation eggs into the South American and WTO baskets, and now its export market share is threatened by the Doha Round paralysis, the Latin American Alianza del Pacífico, and the US-led initiatives for a Trans-Pacific Partnership and a trade and investment agreement with the EU. Paradoxically, this alarming situation opens a window of opportunity. There is a mounting national consensus on the need to tackle head-on the country’s and its industries’ lack of competitiveness. That means finding a solution to the much-decried ‘Brazil Cost’ and stimulating private-sector investment. It also entails an aggressive trade-negotiating stance in order to secure better access to foreign markets and to foster more competition in the domestic one. The most promising near-term goal would be the conclusion of the EU–Mercosur trade talks. A scenario to overcome the paralysis of these negotiations could trail two parallel paths: bilateral EU–Brazil agreements on ‘anything but trade’ combined with a sequencing of the EU–Mercosur talks where each member of the South American bloc could adopt faster or slower liberalisation commitments and schedules.

The Social Impact of Migration and the Notion of Citizenship for the EU. Ensuing challenges and opportunities for the Union. CEPS Commentaries, 13 March 2014

Documenting the unwelcoming treatment extended by government officials to the poorest EU citizens from other member states, including denying them their EU rights, Elspeth Guild censures these officials for shattering the principle of equality of citizens and of disaggregating Europe into nationals of the member states who can be treated differently simply on the basis of their origins.

Government failure, opposition success? Electoral performance in Portugal and Italy at the time of the crisis. Jean Monnet Occasional Paper 05/2014

The costs of the crisis in Southern European countries have not been only economic but political. Economic crises tend to lead to government instability and termination while political challengers are expected to exploit this contingent window of opportunity to gain an advantage over incumbents in national elections. The current crisis seems to make no exception, looking at the results of the general elections recently held in Southern Europe. However, this did not always lead to a clear victory of the main opposition parties. In most of the elections, in fact, the incumbent parties’ loss did not coincide with the official opposition’s gain. The extreme case is represented by Italy, where both the outgoing government coalition led by Silvio Berlusconi – setting aside for the moment the technocratic phase – and its main challenger, the centre left coalition, ended up losing millions of voters and a new political force, the Five Star Movement, obtained about 25 per cent of votes. On the opposite side there is Portugal. Only in Portugal did the vote increase for the centre right PSD, in fact, exceed the incumbent socialists’ loss. The present work aims at exploring the factors which might account for this significant divergence between the two cases.

The Catholic Identity of Malta after Ten Years of Membership in the European Union: Challenges and Prospects. Occasional Paper 2/2014

Introduction. Ten years have elapsed since Malta’s accession in the European Union. One can still recall vividly the intense and acrimonious campaign prior to the membership referendum and the ensuing electoral victory that confirmed the Nationalist Party (PN) in power under the leadership of Edward Fenech Adami in 2003. In both cases the Maltese voted in favour of entry into the EU. During both exercises in democracy the Maltese were exposed to the rhetoric of both prophets of doom and prophets of plenty. For the former accession meant a loss of national and territorial independence, for the latter it meant the beginning of opportunity for all and, in some cases, the answer to all of Malta’s woes. Now, ten years later, a further appraisal of Malta’s membership and place in the European Union is called for. The purpose of this paper, however, is to reflect upon how this membership has affected the Roman Catholic Church in Malta and what prospects lie ahead for the Catholic community within Maltese society that remains in a state of constant flux on both the social and the religious level. It traces the major events that have accelerated the transformation of Malta into a secular society. The paper describes how these events, together with pressures that are being brought to bear by secular movements upon Maltese society, are profoundly affecting its Catholic identity and redrawing its moral landscape. It also discusses ways and means by which the Catholic Church in Malta can address these challenges and contribute towards the construction of a more humane Maltese society. In order to achieve this, it must first and foremost remain a coherent witness of a faith that is forever alive, dynamic and relevant.

Addressing climate change under preferential trade agreements: Towards alignment of carbon standards under the Transatlantic Trade and Investment Partnership

With its wide coverage of economic spheres and the variety of trade and investment measures currently under negotiation, the Transatlantic Trade and Investment Partnership opens windows of opportunity for advancing action on climate change. We examine possible avenues and international trade law implications for an alignment of carbon-related standards between the EU and the US. We compare EU and US carbon emissions standards for cars and argue that negotiators should strive for a mutual recognition of their equivalence for a transitional period, while pursuing the goal of full harmonization at the level of the highest standards of two parties at some date in the future. This could be a way to balance between economic and environmental interests and harness economic incentives for the benefit of climate.

Toward alignment of carbon standards under the Transatlantic Trade and Investment Partnership

With its wide coverage of economic spheres and the variety of trade and investment measures currently under negotiation, the Transatlantic Trade and Investment Partnership (TTIP) opens windows of opportunity for climate change mitigation and adaptation. The paper examines the possible avenues and the WTO law implications for the alignment of emissions standards between the European Union (EU) and United States of America (US). Looking particularly at the automobile sector, it argues that TTIP negotiators should strive for the mutual recognition of equivalence of EU and US car emissions standards, while pursuing full harmonisation in the long term. It concludes that the preferential trade agreement (PTA) status of TTIP would not be able to exempt measures taken for regulatory convergence from compliance with applicable WTO rules, particularly the rules of the WTO’s Agreement on Technical Barriers to Trade (TBT). Furthermore, the EU and the US would not be able to ignore requests for the recognition of equivalence of third countries’ standards and would need to provide the grounds upon which they assess third countries’ standards as not adequately fulfilling the objectives of their own regulations and therefore rejecting them.

Managerialism at the bottom of the pyramid: a case study in Brazil

Nas últimas décadas, a Base da Pirâmide tem sido cada vez mais debatida entre líderes ocidentais como a nova terra das oportunidades. Com o advento do neoliberalismo no campo do desenvolvimento na década de 1990, o papel da sociedade civil e, em particular, o de Organizações Não-Governamentais, passou a ser enfatizado como sendo central nas estratégias ocidentais no "Sul" do mundo. Os atores do desenvolvimento, no entanto, muitas vezes abordaram essas questões utilizando perspectivas tradicionais, que estavam geralmente fora de contexto. A tese foca na controvérsia em torno do uso de técnicas de gestão em cenários que diferem daqueles nos quais estas ferramentas têm sido desenvolvidas. Em particular, ela procura compreender em que medida o gerencialismo - a ideologia da gestão - está a influenciando as atividades de uma Organização Não-Governamental brasileira, a Galpão Aplauso. O estudo, usando uma estrutura teórica, analisa o relacionamento entre a ONG e seus parceiros, sublinhando os resultados de conflitos ideológicos. No geral, descobriu-se como o encontro das perspectivas do Norte e do Sul originou alguns debates que levaram, em parte, à aceitação de ideias gerencialistas, tais como a replicabilidade e sistematização de processos, enquanto que em alguns casos, eles intensificaram a resistência da ONG sobre conceitos como sustentabilidade financeira e transformação em um negócio social.