The Ne Bis In Idem Principle in Tax Law: European and Italian Frameworks

In the national and supranational legal area, the need to address the ne bis in idem principle is justified by the growing interest aroused by the most recent pronouncements of the European Courts. The principle prohibits anyone who has already been acquitted or convicted in a previous trial from being tried again. Moreover, it has become a fundamental right enshrined in the European Convention on Human Rights and the Charter of Fundamental Rights of the EU. The interest in the issue also derives from the need to understand whether the approach of the Italian legal system – or any other similar national order – can be considered compliant with European tax law and case law, based on the definitions of criminal and tax offences. Thus, talking about a European legal space means rethinking the idea of punitive power in a dimension that tends to be ‘solidarity-based’. The State can consider itself impervious to repressive demands from outside but is instead called to cooperate actively to safeguard its own guarantees. The traditional self-referential conception of criminal repression effectively summarised in the expression ‘punitive sovereignty’ gives way to an idea of jurisdiction that draws directly from the principle of mutual recognition. In this scenario, the profile of the protection of the individual from the risk of a duplication of the exercise of punitive power for the same fact in different states assumes the role of the first magnitude. Hence, there is a need to act on two levels at the same time: to seek solutions aimed at resolving possible conflicts of jurisdiction (prohibition of competing prosecutions for the same fact), and to attribute, within each Member State, preclusive effects to the previously judged foreigner (ne bis in idem)

Chapter La riforma delle risorse proprie e la possibile introduzione di un tributo europeo

In the European Union, negotiations on the financial perspectives and the determination of the Union's own resources focus mainly on the amount of the individual states' contributions, and much less on the Union's fiscal competence. This weakens the Union's ability to conduct ambitious long-term policies, potentially mortgaging its very raison d'être. Recent developments related to the COVID-19 crisis (and beyond) seem to open a window for future changes. The European tax is an issue that provokes a wide debate at both the European and national levels, and not only of a political nature, between sovereignists and federalists, but also on the technical-legal-constitutional modalities that such a change would imply. For this reason, it is useful to present a structured analysis first of the financial instruments assigned to the EU, then of a reform of own resources and, finally, of the possibility of envisaging the birth of a European tax, albeit with an awareness of the limits of such a reform with regard to the current constitutional set-up of the European Union. Consequently, it will also be necessary to ask what kind of tax would be appropriate for this purpose

WHT-PARTNERS

Desde sus orígenes, tanto el cultivo de vides en nuestra provincia, como la producción de vinos y su comercialización, han ido evolucionando y atravesando diversidad de circunstancias y coyunturas. Desde la antigua producción artesanal y el consumo interno local, hasta la posición destacada de nuestros vinos a nivel internacional, con Mendoza a la cabeza de la producción nacional, hay un mundo de diferencias. Sin embargo, los tiempos actuales demandan una nueva visión y proyección, acorde a las necesidades globales. En este contexto entonces es que elaboramos la presente investigación, tendiente a constituirse en un aporte para que los productores se acerquen a las nuevas herramientas que desde las legislaciones y los recursos tecnológicos modernos pueden utilizar para acercarse a los mercados internacionales. Aunque aún hay camino que recorrer, ya que los costos todavía se ven perjudicados por las mecánicas cambiarias tan variables de nuestro país, sin embargo creemos que dichos problemas en algún momento se verán favorecidos por nuevas coyunturas, y para ese entonces es necesario que los productores - exportadores se encuentren ya preparados y familiarizados con las herramientas que se les proporciona.Fil: Fedele, Stefania Natalí. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Sese, Agustina. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment

Abstract Aim Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. Methods A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland–Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. Results From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538–0.686), PgR (k0.659; 95% CI, 0580–0.737), Ki-67 (k0.609; 95% CI, 0.534–0.684) and grading (k0.669; 95% CI, 0.569–0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444–0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. Conclusions In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results

Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports

<p>Abstract</p> <p>Background</p> <p>Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.</p> <p>Methods and Results</p> <p>we report on two patients affected by MRKH syndrome in which array-CGH analysis disclosed an identical deletion spanning 1.5 Mb of genomic DNA at chromosome 17q12. One patient was affected by complete absence of uterus and vagina, with bilaterally normal ovaries, while the other displayed agenesis of the upper part of vagina, right unicornuate uterus, non cavitating rudimentary left horn and bilaterally multicystic kidneys. The deletion encompassed two candidate genes, <it>TCF2 </it>and <it>LHX1</it>. Mutational screening of these genes in a selected group of 20 MRKH females without 17q12 deletion was negative.</p> <p>Conclusion</p> <p>Deletion 17q12 is a rare albeit recurrent anomaly mediated by segmental duplications, previously reported in subjects with developmental kidney abnormalities and diabetes. The present two patients expand the clinical spectrum associated with this imbalance and suggest that this region is a candidate locus for a subset of MRKH syndrome individuals, with or without renal defects.</p

Human Herpesvirus 8 and Pulmonary Hypertension

Human herpesvirus 8 (HHV-8) antibodies were detected in 1 of 33 patients with pulmonary hypertension (including in 1 of 16 with idiopathic pulmonary arterial hypertension), 5 of 29 with cystic fibrosis, and 3 of 13 with interstitial lung disease. No relationship between HHV-8 infection and pulmonary hypertension was found

Human Herpesvirus 8 and Pulmonary Hypertension

El presente trabajo de investigación tuvo como objetivo evaluar el nivel de conocimiento sobre salud bucal y su relación con la prevalencia de gingivitis en embarazadas que acuden al servicio de gineco-obstericia del Hospital Camaná. Las técnicas usadas fueron el cuestionario y observación clínica; se aplicó un formulario de conocimiento en salud bucal a 100 gestantes que asistieron a dicho hospital en los meses de Junio y Julio. Para determinar la afectación de gingivitis se aplicó una ficha de observación, previa evaluación clínica, en donde se indicó el índice gingival de Löe y Silness de cada individuo. Los resultados indican que la mayor parte de gestantes presentaron un conocimiento regular en salud bucal con 63% y en cuanto a la prevalencia de gingivitis encontrada en el grupo evaluado de un 49% con inflamación leve, seguido por una inflamación severa con 25%. Se concluyó gracias a la prueba de chi cuadrado que la Gingivitis y el nivel de conocimiento sobre salud bucal presentaron relación estadística significativa (P<0.05) por lo que se rechaza la hipótesis nula y se aprueba la alterna. Finalmente se insta a implementar programas y charlas de salud bucal dirigidas a gestantes para lograr una cultura preventiva óptima. Palabras clave: Nivel conocimiento, salud bucal, gingivitis, gestantes

Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential

Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition, this novel method results in increased numbers of DA neurons that in vitro show characteristic electrophysiological properties of nigrostriatal DA neurons, produce high levels of dopamine, and integrate into host mice when grafted in vivo. Thus, we describe a robust method for producing human mesencephalic DA neurons from hiPSCs

Ropinirole and pramipexole promote structural plasticity in human iPSC- derived dopaminergic neurons via BDNF and mTOR signaling

The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs). Two hiPSC clones from healthy donors were differentiated into midbrain DA neurons. Ropinirole and pramipexole produced dose-dependent increases of dendritic arborization and soma size after 3 days of culture, effects antagonized by the selective D3R antagonists SB277011-A and S33084 and by the mTOR pathway kinase inhibitors LY294002 and rapamycin. All treatments were also effective in attenuating the D3R-dependent increase of p70S6-kinase phosphorylation. Immunoneutralisation of BDNF, inhibition of TrkB receptors, and blockade of MEK-ERK signaling likewise prevented ropinirole-induced structural plasticity, suggesting a critical interaction between BDNF and D3R signaling pathways. The highly similar profiles of data acquired with DA neurons derived from two hiPSC clones underpin their reliability for characterization of pharmacological agents acting via dopaminergic mechanisms

Multicentre harmonisation of a six-colour flow cytometry panel for naïve/memory T cell immunomonitoring

Background. Personalised medicine in oncology needs standardised immunological assays. Flow cytometry (FCM) methods represent an essential tool for immunomonitoring, and their harmonisation is crucial to obtain comparable data in multicentre clinical trials. The objective of this study was to design a harmonisation workflow able to address the most effective issues contributing to intra- and interoperator variabilities in a multicentre project. Methods. The Italian National Institute of Health (Istituto Superiore di Sanita, ISS) managed a multiparametric flow cytometric panel harmonisation among thirteen operators belonging to five clinical and research centres of Lazio region (Italy). The panel was based on a backbone mixture of dried antibodies (anti-CD3, anti-CD4, anti-CD8, anti-CD45RA, and anti-CCR7) to detect naive/memory T cells, recognised as potential prognostic/predictive immunological biomarkers in cancer immunotherapies. The coordinating centre distributed frozen peripheral blood mononuclear cells (PBMCs) and fresh whole blood (WB) samples from healthy donors, reagents, and Standard Operating Procedures (SOPs) to participants who performed experiments by their own equipment, in order to mimic a real-life scenario. Operators returned raw and locally analysed data to ISS for central analysis and statistical elaboration. Results. Harmonised and reproducible results were obtained by sharing experimental set-up and procedures along with centralising data analysis, leading to a reduction of cross-centre variability for naive/memory subset frequencies particularly in the whole blood setting. Conclusion. Our experimental and analytical working process proved to be suitable for the harmonisation of FCM assays in a multicentre setting, where high-quality data are required to evaluate potential immunological markers, which may contribute to select better therapeutic options