Self-Defeating Subsidiarity

In this paper we analyze the factors that should be considered when allocating a given policy function at a particular level of government and how these factors affect the growth and evolution of multi-level governments. After discussing the interplay of economies of scale, economies of scope, and heterogeneity of preferences in determining the optimal level of legal intervention, we show that the subsidiarity principle can have mixed effects as a firewall against progressive centralization. Our economic model of subsidiarity reveals that once some functions become centralized, further centralization becomes easier and often unavoidable. Contrary to its intended function, a piecemeal application of the subsidiarity principle can trigger a path-dependent avalanche of centralization, turning subsidiarity into a self-defeating statement of principle

Accuracy of Verdicts under Different Jury Sizes and Voting Rules

Juries are a fundamental element of the criminal justice system. In this article, we model jury decision making as a function of two institutional variables: jury size and voting requirement. We expose the critical interdependence of these two elements in minimizing the probabilities of wrongful convictions, of wrongful acquittals, and of hung juries. We find that the use of either large nonunanimous juries or small unanimous juries offers alternative ways to maximize the accuracy of verdicts while preserving the functionality of juries. Our framework, which lends support to the elimination of the unanimity requirement in the presence of large juries, helps appraise US Supreme Court decisions and state legal reforms that have transformed the structure of American juries

Novel agents for acute myeloid leukemia

Acute myeloid leukemia (AML) is a complex hematological disease characterized by genetic and clinical heterogeneity. Recent advances in the understanding of AML pathogenesis have paved the way for the development of new agents targeting specific molecules or mechanisms that contribute to finally move beyond the current standard of care, which is \u201c3 + 7\u201d regimen. In particular, new therapeutic options such as targeted therapies (midostaurin and enasidenib), monoclonal antibodies (gemtuzumab ozogamicin), and a novel liposomal formulation of cytarabine and daunorubicin (CPX-351) have been recently approved, and will be soon available for the treatment of adult patients with AML. In this review, we will present and describe these recently approved drugs as well as selected novel agents against AML that are currently under investigation, and show the most promising results as monotherapy or in combination with chemotherapy. The selection of these emerging treatments is based on the authors\u2019 opinion

rates of latent tuberculosis infection using different diagnostica test

Background.The interferon−g−release assays (IGRA) are emerging as an attractive alternative to the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI).The absence of a gold standard for LTBI hampers the assessment of any diagnostic test. Methods.In a prospective study,229 patients (mean age 35.5±24.6 y) from different ward of the Hospital (Respiratory Diseases,Dermatology, Rheumatology, Pediatrics, Infectious Diseases, Hematology and Transplant Unit) were simultaneously tested for a suspect of either LTBI or active tuberculosis using all commercially available diagnostics: TST,QuantiFERON−TB Gold (QFT−2G), QuantiFERON−TB Gold In−Tube(QFT−3G) and T−SPOT.TB(TS.TB). Results. 42(18.3%),37(16.2%),59(25.8%) and 79(34.5%) patients were positive with TST,QFT−2G,QFT−3G and TS.TB, respectively.TS.TB(p<0.001) and QFT−3G(p=0.016) provided more positive results than TST, while no difference was found for TST and QFT−2G(p=0.53).All IGRA showed a good overall agreement (TS.TB vs QFT−2G,k=0.55; TS.TB vs QFT−3G,k=0.72;QFT−2G vs QFT−3G, k=0.62). In 22 subjects (9.6%) QFT−3G was positive and QFT−2G negative. Indeterminate results were more frequent with QFT−2G(18.3%) and QFT−3G (12.7%) than with TS.TB(1.3%,p<0.0001). Conclusion. Rates of LTBI as detected by different diagnostic tests may have significant variations. Performances of various IGRA formats were variable in this population

mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus

Background: Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods: Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results: Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions: Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting

Mast Cells in Peritoneal Fluid From Women With Endometriosis and Their Possible Role in Modulating Sperm Function

Endometriosis is a local pelvic inflammatory process, frequently associated with infertility, with altered function of immune-related cells in the peritoneal environment. Mast cells are known to be key players of the immune system and have been recently involved in endometriosis and in infertility, with their mediators directly suppressing sperm motility. In this study, we evaluated the mast cell population and their mediators in the peritoneal fluid of infertile patients with endometriosis and their impact on human sperm motility. Peritoneal fluids, collected by laparoscopy from 11 infertile patients with endometriosis and 9 fertile controls were evaluated for the presence of mast cells, tryptase levels and their effect on sperm motility. Furthermore, an in vitro model of mast cells-sperm interaction in peritoneal fluid was set up, using LAD2 cell line as a mast cell model, and analyzed from a functional as well as a morphological point of view. Mast cell peritoneal fluid population and its main mediator, tryptase, is more represented in endometriosis confirming an involvement of these cells in this disease. Anyway it appears unlikely that tryptase enriched peritoneal fluid, which fails to inhibit sperm motility, could contribute to endometriosis associated infertility. Despite of this, sperm interaction with the mast cell surface (LAD2) induced a significantly mast cell-degranulation response in the peritoneal fluid from endometriosis which could directly modulate sperm function other than motility. This evidence lead us to suppose that there is, between these elements, an interrelationship which deserves further studies

A case of hemorrhagic shock due to massive upper gastrointestinal bleeding: from the differential diagnosis to the correct management

Upper Gastro-Intestinal Bleeding (UGIB) spans from minor bleeding to life-threatening events. Identification of early signs of shock, proper management of hemodynamically unstable patients, and correct risk stratification are essential for an appropriate diagnostic workup and therapy. This case reports a young man admitted to the emergency department with haematemesis. His medical history was unremarkable, without any risk factors for gastrointestinal bleeding. A few hours after admission, further episodes of haematemesis occurred, and the patient's condition rapidly deteriorated to irreversible shock. A contrast-enhanced computed tomography (CECT) revealed morphological features of chronic liver disease and oesophagal varices. The patient underwent upper gastrointestinal endoscopy, confirming oesophagal varices with massive bleeding. Although promptly applied, endoscopic hemostasis was ineffective, and the patient died twenty-four hours after admission. Based on this case, we reviewed the diagnostic and therapeutic approaches for patients with massive UGIB and provided a practical approach to this life-threatening emergency

Imaging-based indices combining disease severity and time from disease onset to predict COVID-19 mortality: A cohort study

Background: COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care. Purpose: The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED). Materials and methods: All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort. Results: Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models. Conclusion: Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation