the role of premiums and discounts in business valuation evidence from the italian context

The valuation of a (non-totalitarian) shareholding in capital stock is characterized by some critical conditions, which are mainly related to the fact that the transfer or acquisition of the same can determine the transfer of control from one subject to another. It follows that the value of the investment can not simply be equal to the proportional value of the share capital, but should include premiums or discounts. Discounts and premiums do not just affect the value of a company; they play a crucial role in influencing a host of other factors and conditions that can make or break a deal. When it comes to business valuations, it is the business appraiser's responsibility to be intimately knowledgeable with every aspect of discounts and premiums: the different types, the situations when they may or may not apply, and how to quantify them. The paper has a twofold approach: on the one hand, it analyzes the main reference literature on the definition and characteristics of premiums and discounts and the recognition and quantification of the same; on the other, subsequently, it examines the behavior adopted by the Italian professional practice in recognition and appreciation of prizes and discounts

Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe : an ERA Registry study

Background The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. Methods Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. Results The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]. Conclusion This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe.Peer reviewe

Stakeholders perceptions of endangered Egyptian vulture: insights for conservation

The inclusion of perceptions, interests and needs of stakeholders in biodiversity conservation is critical for the long-term protection of endangered species. Yet, the social dimensions of endangered species conservation are often overlooked. We examined the social perceptions of the conservational importance of the globally endangered Egyptian vulture (Neophron percnopterus) in one of the most important breeding areas worldwide: the Bardenas Reales Protected Area, northern Spain. We assessed the factors that influence the stakeholders' views of its conservation importance and identified the management strategies that would have social support. We found that the understandings of the Egyptian vulture differed among stakeholders. Hunters had the highest level of knowledge about its presence, threatened status and role as provider of ecosystem services. Livestock keepers recognized the worth of the Egyptian vulture for carcass removal, whereas other regulating services (e.g. biological control) were frequently acknowledged by tourists. Hunters and livestock keepers were more critical about the effectiveness of ongoing conservation strategies for preserving the Egyptian vulture than tourists. Moreover, each stakeholder group identified different actions for the conservation of the Egyptian vulture in the area. The consideration of the diversity of conservation actions suggested by stakeholders could catalyze broader support for the preservation of the Egyptian vultureinfo:eu-repo/semantics/publishedVersio

C-Terminal Extension of the Yeast Mitochondrial DNA Polymerase Determines the Balance between Synthesis and Degradation

Saccharomyces cerevisiae mitochondrial DNA polymerase (Mip1) contains a C-terminal extension (CTE) of 279 amino acid residues. The CTE is required for mitochondrial DNA maintenance in yeast but is absent in higher eukaryotes. Here we use recombinant Mip1 C-terminal deletion mutants to investigate functional importance of the CTE. We show that partial removal of the CTE in Mip1Δ216 results in strong preference for exonucleolytic degradation rather than DNA polymerization. This disbalance in exonuclease and polymerase activities is prominent at suboptimal dNTP concentrations and in the absence of correctly pairing nucleotide. Mip1Δ216 also displays reduced ability to synthesize DNA through double-stranded regions. Full removal of the CTE in Mip1Δ279 results in complete loss of Mip1 polymerase activity, however the mutant retains its exonuclease activity. These results allow us to propose that CTE functions as a part of Mip1 polymerase domain that stabilizes the substrate primer end at the polymerase active site, and is therefore required for efficient mitochondrial DNA replication in vivo

Assessing disease activity of rheumatoid arthritis patients and drug-utilization patterns of biologic disease-modifying antirheumatic drugs in the Tuscany region, Italy

Introduction: The disease activity associated with the drug-utilization patterns of biologic Disease Modifying Anti-Rheumatic Drugs (DMARDs) is poorly investigated in real-world studies on rheumatoid arthritis (RA) patients. To investigate the relationship between biologic DMARD initiation/discontinuations in RA patients identified in the healthcare administrative databases of Tuscany and the Disease Activity Score 28 (DAS28) reported in the medical charts.Methods: This retrospective population-based study included RA’s first-ever biologic DMARD users of the Pisa University Hospital from 2014 to 2016. Patients were followed up until 31 December 2019. We evaluated the DAS28 recorded before (T0) and after (T1) the biologic DMARD initiation and before (TD0) and after (TD1) discontinuations. Patients were classified as “off-target” (DAS28 > 3.2) or “in-target” (DAS28 ≤ 3.2). We described the disease activity trends at initiation and discontinuation.Results: Ninety-five users were included (73 women, mean age 59.6). Among 70 patients (74%) with at least three DAS28 measures, 28 (40.0%) were off-target at T0 and 38 (54.3%) in-target at T1. Thirty-three (47%) patients had at least one discontinuation, among those with at least three DAS28 assessments. In the disease activity trend, disease stability or improvement was observed in 28 out of 37 (75.7%) patients at initiation and in 24 out of 37 (64.9%) at discontinuation.Discussion: Biologic DMARD discontinuations identified in the healthcare administrative databasese of Tuscany are frequently observed in situations of controlled RA disease. Further studies are warranted to confirm that these events can be used in studies using healthcare administrative databases as proxies of treatment effectiveness

Polymorphic variants of SCN1A and EPHX1 influence plasma carbamazepine concentration, metabolism and pharmacoresistance in a population of Kosovar Albanian epileptic patients

Aim The present study aimed to evaluate the effects of gene variants in key genes influencing pharmacokinetic and pharmacodynamic of carbamazepine (CBZ) on the response in patients with epilepsy. Materials & Methods Five SNPs in two candidate genes influencing CBZ transport and metabolism, namely ABCB1 or EPHX1, and CBZ response SCN1A (sodium channel) were genotyped in 145 epileptic patients treated with CBZ as monotherapy and 100 age and sex matched healthy controls. Plasma concentrations of CBZ, carbamazepine-10,11-epoxide (CBZE) and carbamazepine-10,11-trans dihydrodiol (CBZD) were determined by HPLC-UV-DAD and adjusted for CBZ dosage/kg of body weight. Results The presence of the SCN1A IVS5-91G>A variant allele is associated with increased epilepsy susceptibility. Furthermore, carriers of the SCN1A IVS5-91G>A variant or of EPHX1 c.337T>C variant presented significantly lower levels of plasma CBZ compared to carriers of the common alleles (0.71±0.28 vs 1.11±0.69 μg/mL per mg/Kg for SCN1A IVS5-91 AA vs GG and 0.76±0.16 vs 0.94±0.49 μg/mL per mg/Kg for EPHX1 c.337 CC vs TT; PG showed a reduced microsomal epoxide hydrolase activity as reflected by a significantly decreased ratio of CBZD to CBZ (0.13±0.08 to 0.26±0.17, pT SNP and SCN1A 3148A>G variants were not associated with significant changes in CBZ pharmacokinetic. Patients resistant to CBZ treatment showed increased dosage of CBZ (657±285 vs 489±231 mg/day; P<0.001) but also increased plasma levels of CBZ (9.84±4.37 vs 7.41±3.43 μg/mL; P<0.001) compared to patients responsive to CBZ treatment. CBZ resistance was not related to any of the SNPs investigated. Conclusions The SCN1A IVS5-91G>A SNP is associated with susceptibility to epilepsy. SNPs in EPHX1 gene are influencing CBZ metabolism and disposition. CBZ plasma levels are not an indicator of resistance to the therapy

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Asedios al archivo, la literatura, los territorios, las pedagogías y la creación

Lenguajes de la memoria y los Derechos Humanos III. Asedios al archivo, la literatura, los territorios, las pedagogías y la creación está integrado por un conjunto de trabajos cuyos ejes temáticos son auscultados desde el suelo presente, necesario, insistente, heteroglósico, en continua redefinición. El libro fue concebido en un momento atravesado por el influjo del abismo producido por el gobierno de la derecha en Argentina y en América Latina, en el interregno 2015-2019, y culminado durante la pandemia Covid 19, que azota al mundo con millones de muertos e infectados.Fil: Ares, María Cristina. Universidad de Buenos Aires. Departamento de Letras; Argentina.Fil: Bracaccini Acevedo, María. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades; Argentina.Fil: Cella, Susana. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina.Fil: Cornavaca, María Trinidad. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina.Fil: Corral, María Manuela. Universidad Nacional de Córdoba. Facultad de Lenguas; Argentina.Fil: Crenzel, Emilio. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Da Silva Catela, Ludmila. Universidad Federal de Río de Janeiro; Brasil.Fil: Díaz, Marcelo. Universidad Nacional de Río Cuarto; Argentina.Fil: Ferraro, Paula Daniela. Universidad Federal Fluminense; Brasil.Fil: Ferrada Rau, Rocío Nili. Universidad de Chile; Chile.Fil: Garbero, Vanesa. Universidad de Buenos Aires; Argentina.Fil: García, Díaz. Universidad Nacional Autónoma de México; México.Fil: Giraldi Dei Cas, Norah. Universidad de Lille; Francia.Fil: Gutiérrez, Carlos Arturo. Universidad Nacional de Colombia; Colombia.Fil: Kozameh, Alicia. Chapman University. Departamento de Inglés; Estados Unidos.Fil: Magrin, Natalia. Universidad Nacional de Córdoba. Facultad de Psicología; Argentina.Fil: Inchauspe, Leandro. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Martínez, Carlos Dámaso. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Letras; Argentina.Fil: Mercado, Mónica. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Artes Visuales; Argentina.Fil: Merro, Agustina. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Letras; Argentina.Fil: Mohaded, Ana. Universidad Nacional de Córdoba. Facultad de Artes. Departamento Académico de Cine y Televisión; Argentina.Fil: Montes, Alicia. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina.Fil: Muñoz Leppe, Olga Elvira. Universidad Metropolitana de Ciencias de la Educación; Chile.Fil: Palma Solís, Jennifer Luz. Universidad de Chile; Chile.Fil: Pino, Mirian. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Letras; Argentina.Fil: Rabanal Gatica, Damaso. Universidad Austral de Chile; Chile.Fil: Reati, Fernando. Georgia State University; Estados Unidos.Fil: Reyes, Manuela. Universidad Nacional de Villa María; Argentina.Fil: Rocchietti, Luciana. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación; Argentina.Fil: Saint Bonet, María Virginia. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Letras; Argentina.Fil: Schwenke, Gonzalo. Universidad Austral de Chile; Chile.Fil: Semilla Durán, María Angélica. Universidad Central de Barcelona; España.Fil: Solis, Ana Carol. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Sosa San Martín, Gabriela. Universidad de la República. Facultad de Humanidades y Ciencias de la Educación; Uruguay.Fil: Suppo, Carina Noemí. Universidad Nacional de Rosario; Argentina.Fil: Vásquez, Malva Marina. Universidad de Chile; Chile.Fil: Vassallo, Celeste. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Letras; Argentina.Fil: Wild, Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias de la Comunicación; Argentina