Gli istituti deflattivi del contenzioso tributario. Stato attuale e criticit\ue0

ll legislatore tributario, soprattutto a partire dal 1997, ha ritenuto di affermare in maniera sempre pi\uf9 esplicita la necessit\ue0 della collaborazione e del contraddittorio nel rapporto tra Fisco e contribuente, soprattutto in considerazione del fatto che la mancanza di un confronto tra le parti finisce per facilitare la creazione di situazioni conflittuali, che sfociano nella attivazione di posizioni di contenzioso. Sono stati cos\uec introdotti nel nostro ordinamento, gli istituti deflattivi del contenzioso tributario, in base ai quali il contribuente che, trovandosi in una situazione di lite potenziale con gli Uffici, rinuncia al contenzioso e versa l\u2019imposta, ha diritto a sanzioni ridotte nonch\ue9 ad altri vantaggi, compresa una piccola copertura verso possibili futuri accertamenti e la possibilit\ue0 di effettuare il pagamento dilazionato delle somme dovute. Sebbene oggetto di intervento nel corso degli anni, tali istituti presentano ancora numerosi profili critici e ampi margini di miglioramento

Effectiveness and safety of secukinumab in Italian patients with psoriasis: an 84 week, multicenter, retrospective real-world study

Background: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinumab in patients with moderate-to-severe psoriasis. Research design and methods: This 84-week, multicenter (n = 7) retrospective study analyzed data from patients who initiated and received at least 6 months of secukinumab treatment between June 2016 and June 2018 in the Campania region of Italy. Patient demographic and treatment characteristics, duration of treatment and reasons for discontinuation as well as Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores were assessed. Results: 324 patients (63% male, mean age 50.2 years) were enrolled and received a mean 11.7 months of secukinumab treatment. Overall, 9.5% discontinued secukinumab, including 5.2% who discontinued due to secondary inefficacy and 1.8% due to adverse events. PASI, BSA and DLQI scores were significantly improved from baseline at every follow-up visit (p < 0.001) and mean PASI decreased from 15.3 ± 6.3 at baseline to 0.5 ± 1.0 at week 84. Secukinumab had comparable effectiveness in biologic naïve and non-naïve patients. Conclusions: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis

Factors impacting time to total shoulder arthroplasty among patients with primary glenohumeral osteoarthritis and rotator cuff arthropathy managed conservatively with corticosteroid injections

Background The purpose of this study was to identify predictors of the time from initial presentation to total shoulder arthroplasty (TSA) in patients with primary glenohumeral osteoarthritis (OA) and rotator cuff (RTC) arthropathy who were conservatively managed with corticosteroid injections. Methods We conducted a retrospective cohort study of patients who underwent TSA from 2010 to 2021. Kaplan-Meier survival analysis was used to estimate median time to TSA for primary OA and RTC arthropathy patients. The Cox proportional hazards model was used to identify significant predictors of time to TSA and to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was set at P<0.05. Results The cohort included 160 patients with primary OA and 92 with RTC arthropathy. In the primary OA group, median time to TSA was 15 months. Significant predictors of shorter time to TSA were older age at presentation (HR, 1.02; 95% CI, 1.00–1.04; P=0.03) and presence of moderate or severe acromioclavicular joint arthritis (HR, 1.45; 95% CI, 1.05–2.01; P=0.03). In the RTC arthropathy group, median time to TSA was 14 months, and increased number of corticosteroid injections was associated with longer time to TSA (HR, 0.87; 95% CI, 0.80–0.95; P=0.003). Conclusions There are distinct prognostic factors for progression to TSA between primary OA patients and RTC arthropathy patients managed with corticosteroid injections. Multiple corticosteroid injections are associated with delayed time to TSA in RTC arthropathy patients. Level of evidence III

Hippocampal neuroinflammation, functional connectivity, and depressive symptoms in multiple sclerosis

Depression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging. Methods The Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS. Results Patients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio. Conclusions Our results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of the role of inflammatory processes in the pathogenesis of depression more generally

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Unstable Maternal Environment, Separation Anxiety, and Heightened CO2 Sensitivity Induced by Gene-by-Environment Interplay

Background: In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology: Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were crossfostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results: Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2- enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the trait’s stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett x = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions: A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some no

Emergenza sismica nel centro Italia 2016-2017. Secondo rapporto del gruppo operativo SISMIKO. Sviluppo e mantenimento della rete sismica mobile a seguito del terremoto di Amatrice Mw 6.0 (24 agosto 2016, Italia centrale)

La rete sismica temporanea installata dal gruppo operativo INGV SISMIKO a seguito del terremoto del 24 agosto 2016 tra i Monti della Laga e la Valnerina, è stata ampliata nel settore settentrionale a seguito dei forti terremoti avvenuti alla fine del mese di ottobre 2016. Successivamente alle due scosse di Mw 5.4 e 5.9 che il 26 ottobre hanno interessato l’area al confine Marche-Umbria tra i Comuni di Castelsantangelo sul Nera (MC), Norcia (PG) e Arquata del Tronto (AP), la geometria della rete è stata estesa di circa 25 km verso nord con l’attivazione di ulteriori tre stazioni temporanee di cui una, da subito, disposta per la trasmissione dei dati in tempo reale e per l’inserimento nel sistema di sorveglianza sismica dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV). Un’ultima stazione è stata inoltre installata nei pressi di Campello del Clitunno in provincia di Perugia ad ovest della sequenza, a seguito del terremoto Mw 6.5 che la mattina del 30 ottobre ha interessato l’intera area già fortemente provata dalla sequenza in corso; questo è stato il più forte terremoto registrato negli ultimi 30 in Italia. A circa 5 mesi dall’inizio dell’emergenza sismica, la rete temporanea conta quindi 23 stazioni che da metà dicembre sono tutte trasmesse in tempo reale ai diversi centri di acquisizione INGV, ovvero Milano, Ancona e Grottaminarda ma soprattutto Roma dove i dati vengono contestualmente archiviati nell’European Integrated Data Archive (EIDA) e integrati nel sistema di monitoraggio e sorveglianza sismica dell’INGV; per la sorveglianza sono incluse solo parte delle stazioni. Nelle ultime settimane, le attività di campagna del gruppo operativo SISMIKO sono state costantemente focalizzate alla cura e alla manutenzione della strumentazione per garantire la continuità della trasmissione e dell’acquisizione dei dati, a volte compromesse da malfunzionamenti legati al maltempo. Alla data di aggiornamento del presente report, non è ancora stata decretata una dismissione o una rimodulazione della geometria della rete sismica temporanea, anche in considerazione della attività sismica in corso a tutt’oggi molto sostenuta. Tutti i dati acquisiti dalle stazioni temporanee SISMIKO, sono distribuiti senza alcun vincolo, al pari dei dati della Rete Sismica Nazionale (RSN, codice di rete IV), ed utilizzati per prodotti scientifici in tempo reale (localizzazioni di sala, calcolo dei Time Domain Moment Tensor -TDMT delle ShakeMaps, ecc) e per l’aggiornamento dei database dell’INGV come l’Italian Seismological Instrumental and Parametric Database (ISIDe) con la revisione del Bollettino Sismico Italiano (BSI), dell’INGV Strong Motion Data (ISMD) e dell’ITalian ACcelerometric Archive (ITACA), dell’European-Mediterranean Regional Centroid Moment Tensors (RCMT) e nei lavori scientifici che utilizzano forme d’onda velocimetriche ed accelerometriche (ri- localizzazioni, studi della sorgente sismica ecc.).Istituto Nazionale di Geofisica e Vulcanologia (INGV)Published1SR. TERREMOTI - Servizi e ricerca per la Societ

Rapporto Preliminare Sulle Attività Svolte Nel Primo Mese Di Emergenza Dal Gruppo Operativo Sismiko A Seguito Del Terremoto Di Amatrice Mw 6.0 (24 Agosto 2016, Italia Centrale)

Sintesi delle attività svolte dal coordinamento delle reti sismiche mobili INGV in emergenza, denominato SISMIKO, nel primo mese della sequenza sismica “Amatrice” seguita al terremoto di Mw 6.0 del 24 agosto 2016 (01:36 UTC). Descrizione della rete sismica implementata e prime analisi dei dati acquisiti. Report on the activities in the first month of emergency by coordination of mobile seismic networks INGV emergency, called SISMIKO, after the Mw 6.0 Amatrice earthquake (August 24th, 2016, central italy). Description of the temporary seismic network implemented and preliminary analysis of the acquired data.INGV DPCPublished1IT. Reti di monitoraggi

SISMIKO:emergency network deployment and data sharing for the 2016 central Italy seismic sequence

At 01:36 UTC (03:36 local time) on August 24th 2016, an earthquake Mw 6.0 struck an extensive sector of the central Apennines (coordinates: latitude 42.70° N, longitude 13.23° E, 8.0 km depth). The earthquake caused about 300 casualties and severe damage to the historical buildings and economic activity in an area located near the borders of the Umbria, Lazio, Abruzzo and Marche regions. The Istituto Nazionale di Geofisica e Vulcanologia (INGV) located in few minutes the hypocenter near Accumoli, a small town in the province of Rieti. In the hours after the quake, dozens of events were recorded by the National Seismic Network (Rete Sismica Nazionale, RSN) of the INGV, many of which had a ML > 3.0. The density and coverage of the RSN in the epicentral area meant the epicenter and magnitude of the main event and subsequent shocks that followed it in the early hours of the seismic sequence were well constrained. However, in order to better constrain the localizations of the aftershock hypocenters, especially the depths, a denser seismic monitoring network was needed. Just after the mainshock, SISMIKO, the coordinating body of the emergency seismic network at INGV, was activated in order to install a temporary seismic network integrated with the existing permanent network in the epicentral area. From August the 24th to the 30th, SISMIKO deployed eighteen seismic stations, generally six components (equipped with both velocimeter and accelerometer), with thirteen of the seismic station transmitting in real-time to the INGV seismic monitoring room in Rome. The design and geometry of the temporary network was decided in consolation with other groups who were deploying seismic stations in the region, namely EMERSITO (a group studying site-effects), and the emergency Italian strong motion network (RAN) managed by the National Civil Protection Department (DPC). Further 25 BB temporary seismic stations were deployed by colleagues of the British Geological Survey (BGS) and the School of Geosciences, University of Edinburgh in collaboration with INGV. All data acquired from SISMIKO stations, are quickly available at the European Integrated Data Archive (EIDA). The data acquired by the SISMIKO stations were included in the preliminary analysis that was performed by the Bollettino Sismico Italiano (BSI), the Centro Nazionale Terremoti (CNT) staff working in Ancona, and the INGV-MI, described below

Le attività del gruppo operativo INGV "SISMIKO" durante la sequenza sismica "Amatrice 2016",

SISMIKO è un gruppo operativo dell’Istituto Nazionale di Geofisica e Vulcanologia (INGV) che coordina tutte le Reti Sismiche Mobili INGVPublishedLecce3T. Sorgente sismica4T. Sismicità dell'Italia8T. Sismologia in tempo reale1SR TERREMOTI - Sorveglianza Sismica e Allerta Tsunami2SR TERREMOTI - Gestione delle emergenze sismiche e da maremoto3SR TERREMOTI - Attività dei Centr