The Historical Turn in Democratization Studies: A New Research Agenda for Europe and Beyond. CES Working Paper Series No. 177, 2010

The paper lays the theoretical and methodological foundations of a new historically-minded approach to the comparative study of democratization, centered on the analysis of the creation, development and interaction of democratic institutions. Historically, democracy did not emerge as a singular coherent whole but rather as a set of different institutions, which resulted from conflicts across multiple lines of social and political cleavage that took place at different moments in time. The theoretical advantage of this approach is illustrated by highlighting the range of new variables that come into focus in explaining democracy's emergence. Rather than class being the single variable that explains how and why democracy came about, we can see how religious conflict, ethnic cleavages, and the diffusion of ideas played a much greater role in Europe's democratization than has typically been appreciated. Above all, we argue that political parties were decisive players in how and why democracy emerged in Europe and should be at the center of future analyses

Development and characterization of the arterial windkessel and its role during left ventricular assist device assistance

Modeling of the cardiovascular system is challenging, but it has the potential to further advance our understanding of normal and pathological conditions. Morphology and function are closely related. The arterial system provides steady blood flow to each organ and damps out wave fluctuations as a consequence of intermittent ventricular ejection. These actions can be approached separately in terms of mathematical relationships between pressure and flow. Lumped parameter models are helpful for the study of the interactions between the heart and the arterial system. The arterial windkessel model still plays a significant role despite its limitations. This review aims to discuss the model and its modifications and derive the fundamental equations by applying electric circuits theory. In addition, its role during left ventricular assist device assistance is explored and discussed in relation to rotary blood pumps

Belief in equality of opportunities and attitudes towards immigrants in Italy: The mediator effect of institutional trust

The thematic area of the research is the populist narrative in Italy and the analysis of the phenomenon through the perception of equality of opportunities, the trust on institutions and the attitudes towards immigrants. In Italy with the growing of national populism there have been witnessed some intolerant attitudes towards immigrants. The differences between majority group and minority group and a discriminating narrative have been observed among the population. We therefore wanted to research the influences and the connections among these constructs. Based on literature review, we found that the relation between equality of opportunities and attitudes towards immigrants has not been deeply studied. The data used in the study are part of the database of European Social Survey (ESS) Round 9. The study includes the analysis of the responses given by two thousand, seven hundred forty-five Italian people to the constructs that constituted the objects of the research. The results showed positive and significant correlations among equality of opportunities beliefs, attitudes towards immigrants and trust in institutions. A simple mediation model was tested and revealed an indirect effect of equality of opportunities beliefs and attitudes towards immigrants through trust in institutions. The implications of the results for the improvements of intergroup contact are discussed.A área temática da pesquisa é a narrativa populista na Itália e a análise do fenômeno através da percepção da igualdade de oportunidades, da confiança nas instituições e das atitudes em relação aos imigrantes. Na Itália, com o crescimento do populismo nacional, testemunharam-se algumas atitudes intolerantes em relação aos imigrantes. As diferenças entre o grupo majoritário e o grupo minoritário e uma narrativa discriminatória foram observadas entre a população. Portanto, queríamos pesquisar as influências e as conexões entre esses enunciados. Com base na revisão da literatura, descobrimos que a relação entre igualdade de oportunidades e atitudes em relação aos imigrantes não foi profundamente estudada. Os dados utilizados no estudo fazem parte da base de dados do European Social Survey (ESS) Round 9. O estudo inclui a análise das respostas dadas por dois mil setecentos e quarenta e cinco italianos as perguntas que constituíram os objetos do pesquisa. Os resultados mostraram correlações positivas e significativas entre crenças de igualdade de oportunidades, atitudes em relação aos imigrantes e confiança nas instituições. Um modelo de mediação simples foi testado e revelou um efeito indireto de crenças de igualdade de oportunidades e atitudes em relação aos imigrantes através da confiança nas instituições. As implicações dos resultados são discutidas

Towards patient-specific modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps

Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique.Background: Ventricular Assist Devices (VADs) insertion is an established treatment for patients with end-stage heart failure waiting for a heart transplant or in need for long-term circulatory support (destination therapy). Rotary blood pumps (RBP) are the most popular devices in view of their size and performance. Pre-operative planning strategy for the insertion of a left ventricular assist device (LVAD) requires a timely discussion at a Multi-Disciplinary Team Meeting (MDT). Clinical-decision making is based according to the needs of the patient and must be processed without delays. Nevertheless, thrombus formation remains a feared complication which affects outcome. VADs operate in a flow regime which is difficult to simulate: the transitional region at the boundary of laminar and turbulent flow (low Reynolds number). Different methods have been used but the best approach remains debatable. Computational Fluid Dynamics (CFD) is an attractive and invaluable tool for the study of the interactions between VADs and the cardiovascular system. The aim of this thesis is three-fold: a) to investigate the use of pressure-volume analysis in a clinical setting through the review of six heart failure patients previously discussed at a MDT meeting with a view to predict or guide further management; b) to review the theory behind modelling approaches to VADs and their interactions with the cardiovascular system for better understanding of their clinical use. Then, an overview of computational fluid dynamics (CFD) is considered as a prelude to its application to the analysis of VADs performance. Additionally, the development of a simplified model of centrifugal pump will be used in initial simulations as preliminary analysis; c) to examine an example of a proof-of-concept pilot patient-specific model of an axial flow pump (HeartMate II) as pre-operative planning strategy in a patient-specific model with a view to identify potential critical areas that may affect pump function and outcome in a clinical setting. Material and Methods: 3D reconstruction from CT-scan images of patients who underwent the insertion of rotary blood pumps, namely HeartWare HVAD and HeartMate II. Ansys Fluent has been used for CFD analysis based on the fundamental governing equations of motion. Blood has been modelled as incompressible, Newtonian fluid with density = 1060 and viscosity = 0.0035 kg/m-s. The laminar and SST models have been used for comparison purposes. The rotational motion of the impeller has been implemented using the moving reference frame (MRF) approach. The sliding mesh method has also been used to account for unsteady interaction between stationary and moving part. The no-slip condition has been applied to all walls, which were assumed to be rigid. Boundary conditions consisting of velocity inlet and pressure outlet of the pump based on different settings and constant rotational speed for the impeller. Pressure-velocity coupling has been based on the coupled scheme. Spatial discretisation consisted of the “least square cell based” gradient for velocity and “PRESTO” or second order for pressure. Second order upwind has been set for the momentum, turbulent kinetic energy and specific dissipation rate. First order implicit has been set for transient formulation. The pseudo transient algorithm (steady state), the high order relaxation term and the warped-face gradient correction have been used to add an unsteady term to the solution equations with the aim to improve stability and enhance convergence. Specific settings have been considered for comparison purposes. Results: Pressure-volume simulation analysis in six advanced heart failure patients showed that an integrated model of the cardiovascular system based on lumped-parameter representation, modified time-varying elastance and pressure-volume analysis of ventricular function seems a feasible and suitable approach yielding a sufficiently accurate quantitative analysis in real time, therefore applicable within the time-constraints of a clinical setting. Lumped-parameter models consist of simultaneous ordinary differential equations complemented by an algebraic balance equation and are suitable for examination of global distribution of pressure, flow and volume over a range of physiological conditions with inclusion of the interaction between modelled components. Higher level lumped-parameter modelling is needed to address the interaction between the circulation and other systems based on a compromise between complexity and ability to set the required parameters to personalise an integrated lumped-parameter model for a patient-specific approach. CARDIOSIM© fulfils these requirements and does address the systems interaction with its modular approach and assembly of models with varying degree of complexity although 0-D and 1-D coupling may be required for the evaluation of long-term VAD support. The challenge remains the ability to predict outcome over a longer period of time. The preliminary CFD simulations with the HeartWare HVAD centrifugal pump demonstrated that it is possible to obtain an accurate analysis in a timely manner to complement the clinical review process. The simulations with the pilot patient-specific model of the HeartMate II axial flow pump revealed that a complex 3D reconstruction is feasible in a timely manner and can be used to generate sufficiently accurate results to be used in the context of a MDT meeting for the purposes of clinical decision-making. Overall, these three studies demonstrate that the time frame of the simulations was within hours which may fit the time constraints of the clinical environment in the context of a MDT meeting. More specifically, it was shown that the laminar model may be used for an initial evaluation of the flow development within the pump. Nonetheless, the k- model offers higher accuracy if the timeline of the clinical setting allows for a longer simulation. Conclusion: This thesis aimed at the understanding of the use of computational modelling as a pre-operative planning strategy and follow up assessment for the treatment of advanced heart failure with rotary blood pumps. The novelty lays in the use of both pressure-volume simulation analysis and 3D flow dynamics studies in VADs with a view to treatment optimisation and outcome prediction within the time constraints of a clinical setting in the context of a MDT meeting. The clinical significance and the contribution to the field is a more targeted approach for different groups of patients and a more quantitative evaluation in the clinical decision process based on a pro-active co-operation between clinicians and scientists reducing the potential for “guess work”. The results of this thesis are a proof-of-concept as a prelude to a potential future implementation of patient-specific modelling within a clinical setting on a daily basis demonstrating a clear clinical significance and contribution to the field. The proposed approach does not consider modelling and simulation as a substitute for clinical experience but an additional tool to guide therapeutic intervention and complement the clinical decision process in which the clinician remains the ultimate decision-maker. Such an approach may well add a different dimension to the problem of heart failure with potential for high return in terms of patient’s outcome and long-term surveillance. The same principles would be applicable to other cardiovascular problems in line with the current concept of “Team Approach” such as the Heart Team, the Structural Heart Team or the Aortic Team. The present work has taken this concept closer to clinical delivery and has highlighted its potential but further work remains to be done in refining the technique

Spontaneous sealing of a type Ia endoleak after ovation stent graft implantation in a patient with on-label aortic neck anatomy

We report a case of an early type Ia endoleak after endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm by Ovation Stent Graft implantation and spontaneously resolved without further reintervention. The patient presents a conical aortic neck, but EVAR was performed within the instruction for use proposed by manufactory. At completion angiography, a low-flow type Ia endoleak was present and left untreated. Computed tomographic angiography performed on the third postoperative day showed infolding of the 2 sealing rings. The patient was dismissed without further treatment. At 3-month follow-up, the leak appeared spontaneously sealed with partial expansion of the 2 rings.We report a case of an early type Ia endoleak after endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm by Ovation Stent Graft implantation and spontaneously resolved without further reintervention. The patient presents a conical aortic neck, but EVAR was performed within the instruction for use proposed by manufactory. At completion angiography, a low-flow type Ia endoleak was present and left untreated. Computed tomographic angiography performed on the third postoperative day showed infolding of the 2 sealing rings. The patient was dismissed without further treatment. At 3-month follow-up, the leak appeared spontaneously sealed with partial expansion of the 2 rings

Open conversion after aortic endograft infection. Caused by colistin-resistant, carbapenemase-producing Klebsiella pneumoniae

A 62-year-old man presented with fever, abdominal pain, and malaise 13 months after emergency endovascular aortic repair. Computed tomographic angiograms showed a periprosthetic fluid and gas collection, so infection was diagnosed. Open conversion was performed, involving endograft explantation and in situ aortic reconstruction. Cultures and the explanted prosthesis were positive for carbapenemase-producing Klebsiella pneumoniae, resistant to colistin. Because of the sparse data on endograft infections caused by this pathogen, we placed the patient on an empiric double-carbapenem regimen for 4 weeks. Symptomatic recovery occurred after 21 days. On the 30th day, we deployed a stent to treat a new pseudoaneurysm. Three years later, the patient had no signs of persistent or recurrent infection. We think that this is the first report of aortic endograft infection caused by colistin-resistant, carbapenemase-producing K. pneumoniae.A 62-year-old man presented with fever, abdominal pain, and malaise 13 months after emergency endovascular aortic repair. Computed tomographic angiograms showed a periprosthetic fluid and gas collection, so infection was diagnosed. Open conversion was performed, involving endograft explantation and in situ aortic reconstruction. Cultures and the explanted prosthesis were positive for carbapenemase-producing Klebsiella pneumoniae, resistant to colistin. Because of the sparse data on endograft infections caused by this pathogen, we placed the patient on an empiric double-carbapenem regimen for 4 weeks. Symptomatic recovery occurred after 21 days. On the 30th day, we deployed a stent to treat a new pseudoaneurysm. Three years later, the patient had no signs of persistent or recurrent infection. We think that this is the first report of aortic endograft infection caused by colistin-resistant, carbapenemase-producing K. pneumoniae

S100B inhibitor pentamidine attenuates reactive gliosis and reduces neuronal loss in a mouse model of Alzheimer's disease

Among the different signaling molecules released during reactive gliosis occurring in Alzheimer’s disease (AD), the astrocytederived S100B protein plays a key role in neuroinflammation, one of the hallmarks of the disease. The use of pharmacological tools targeting S100B may be crucial to embank its effects and some of the pathological features of AD. The antiprotozoal drug pentamidine is a good candidate since it directly blocks S100B activity by inhibiting its interaction with the tumor suppressor p53. We used a mouse model of amyloid beta- (A-) induced AD, which is characterized by reactive gliosis and neuroinflammation in the brain, and we evaluated the effect of pentamidine on the main S100B-mediated events. Pentamidine caused the reduction of glial fibrillary acidic protein, S100B, and RAGE protein expression, which are signs of reactive gliosis, and induced p53 expression in astrocytes. Pentamidine also reduced the expression of proinflammatory mediators and markers, thus reducing neuroinflammation in AD brain. In parallel, we observed a significant neuroprotection exerted by pentamidine on CA1 pyramidal neurons. We demonstrated that pentamidine inhibits A-induced gliosis and neuroinflammation in an animal model of AD, thus playing a role in slowing down the course of the disease

Is type 2 diabetes really resolved after laparoscopic sleeve gastrectomy? Glucose variability studied by continuous glucose monitoring

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (<140 mg/dL) at 120 minutes OGTT. These interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes