Degenerations of twisted maps to algebraic stacks

We give a definition of twisted map to an algebraic stack with projective good moduli space, and we show that the resulting functor satisfies the existence part of the valuative criterion for properness.Comment: 23 pages, comments very welcome

Venous thrombo-embolism (VTE) prevention of patients undergoing total hip and knee replacement: budget impact analysis of apixaban in Italy

BACKGROUND: Venous thromboembolism (VTE) is a common and burdensome cardiovascular condition, frequently leading to severe complications and requiring high-cost healthcare interventions. New oral anticoagulants (nOACs) have demonstrated to be efficacious and safe in VTE prevention of patients undergoing total hip replacement (THR) and total knee replacement (TKR), a condition that is typically associated to cardiovascular disease. The Italian Healthcare Service (SSN) has recently approved the latest nOAC, apixaban. The present article aims to evaluate its economic impact in the perspective of the Italian SSN.METHODS: We conducted a budget impact analysis to estimate clinical outcomes and economic consequences associated to the reimbursement of apixaban, in the prevention of VTE as a consequence of major orthopedic surgery, over a three-year time horizon. In our analysis we compared two alternative scenarios, with apixaban either reimbursed (Scenario B) or not reimbursed (Scenario A) by the Italian SSN, and estimated the difference of healthcare costs between the two scenarios. Only direct healthcare costs have been considered.RESULTS: According to market assumptions, it is estimated that 1.2%, 3.7%, and 6.5% of THR patients, and 1.2%, 3.8% and 6.7% of TKR patients, would be treated with apixaban over the first three years since launch. At the estimated daily cost of apixaban (€2.48/die), this would translate into a budget impact of €14.3 mln, €45.5 mln, and €81.4 mln at years 1, 2 and 3 since launch, respectively. This expenditure would be more than offset by savings, due to: i) reduction of prescriptions of alternative treatment options (other nOACs, low-molecular weight heparins, fondaparinux); ii) reduction of the economic burden attributable of CV complications of VTE. Finally, Scenario B resulted slightly favourable compared to Scenario A, leading to economic savings for about €50 thousands over three years. Sensitivity analyses confirmed findings of the base-case analysis.CONCLUSIONS: Reimbursement of apixaban does not determine a budget impact increase for Italian SSN. Its usage may be considered fully sustainable from a pharmaco-economic viewpoint

Analisi dei movimenti fetali come indicatore relazionale in gravidanze gemellari mono e bicoriali.

2012/2013Lo studio ecografico 4D dei movimenti fetali in gravidanze singole dimostra patterns cinematici con finalità d’azione a partire dalla 22a settimana di gestazione. Un successivo studio su gravidanze gemellari dimostra non solo l’anticipazione della pianificazione motoria dalla 14a settimana, ma anche che il movimento verso il co-gemello non è accidentale, suggerendo che la propensione all’azione socialmente orientata è presente prima della nascita. La presente ricerca è rivolta al confronto ecografico 4D dei movimenti fetali in gravidanze gemellari mono versus bicoriali fino alla 20a settimana (limite tecnico per osservare i movimenti presi in considerazione) e al successivo follow up dei profili di movimento delle stesse coppie di gemelli fino al sesto mese di vita. È stata inoltre valutata la nascita della genitorialità in base all’analisi delle rappresentazioni genitoriali durante e dopo la gravidanza. I partecipanti sono 20 feti: 10 gemelli monocoriali e 10 gemelli bicoriali, con stato clinico di buona salute e 10 madri sane. Lo studio è composto da 2 parti: 1) Osservazione di movimenti fetali videoregistrati secondo un campionamento a frequenze ripetute e fisse, ogni 15 giorni per un periodo di 30 minuti dalla 14a alla 20a settimana di gestazione e poi dopo la nascita fino al sesto mese di vita; 2) Interviste semi strutturate alla coppia con differenti test psicologici. Le videoregistrazioni hanno permesso di rilevare la frequenza dei movimenti dei feti verso se stessi, verso il co-gemello e verso l’esterno (parete uterina e cordone ombelicale). Diversamente, le interviste ed i test psicologici sono stati esaminati nei contenuti emotivi e relazionali dei futuri genitori ai fini di stabilire la qualità del modo di stare in relazione con i propri bambini e lo stile di attaccamento manifestato prima e dopo la nascita. Lo studio è stato finalizzato all’identificazione di eventuali differenze dei profili di movimento tra i co-gemelli in base alla corionicità al fine di fornire importanti informazioni nella comprensione dei fattori che in utero influenzano lo sviluppo dell’intenzionalità e della motricità finalizzata. Una risposta all’obiettivo principale dello studio è stata trovata dimostrando l’esistenza di una reale differenza d’interazione tra i co-gemelli mono e bi-coriali tra la 14a e la 20a settimana di gestazione. Inoltre, abbiamo dimostrato come la nascita della socializzazione in utero nasca già dalla 14a settimana, mostrando una maggior propensione al “movimento sociale” da parte delle gravidanze monocoriali, mantenendo un comportamento costante durante le settimane osservate. Non altrettanto fanno i gemelli bicoriali, questi ultimi, infatti, mostrano uno sviluppo costante del movimento sociale tra la 14a e le 20a settimana di gestazione sovrapponendosi ai fratelli monocoriali solo dalle 20 settimane, come se lo sviluppo di un piano motorio volto all’interazione sociale si sviluppi più tardivamente nei gemelli bicoriali. Sarà importante chiarire questi aspetti sullo sviluppo della socializzazione poiché i modelli sociali, anche pre-natali, potrebbero essere marcatori precoci della comparsa di disturbi dello sviluppo che riguardano la dimensione sociale del comportamento, come ad esempio i disturbi pervasivi dello sviluppo. Per tali motivi è importante continuare e approfondire questo filone integrandolo con studi di cinematica fetale, per imparare a conoscere meglio e a riconoscere precocemente tali marcatori.XXVI Ciclo197

Alles Lüge? Warum Deutschlands Medien so stark - und manchmal doch so angreifbar sind: 28. Februar 2016

Welche Rolle spielen die Medien in Deutschland? Welchen Anteil haben sie am Vertrauensverlust in der Gesellschaft und an der Spaltung, die überall zu beobachten ist? Damit möchte ich mich heute beschäftigen

Imaging and therapy of ovarian cancer: Clinical application of nanoparticles and future perspectives

Despite significant advances in cancer diagnostics and treatment, ovarian cancers (OC) continue to kill more than 150,000 women every year worldwide. Due to the relatively asymptomatic nature and the advanced stage of the disease at the time of diagnosis, OC is the most lethal gynecologic malignancy. The current treatment for advanced OC relies on the synergistic effect of combining surgical cytoreduction and chemotherapy; however, beside the fact that chemotherapy resistance is a major challenge in OC management, new imaging strategies are needed to target microscopic lesions and improve both cytoreductive surgery and patient outcomes. In this context, nanostructured probes are emerging as a new class of medical tool that can simultaneously provide imaging contrast, target tumor cells, and carry a wide range of medicines resulting in better diagnosis and therapeutic precision. Herein we summarize several exemplary efforts in nanomedicine for addressing unmet clinical needs

Dorsal Prefrontal Cortex Impairment in Methoxetamine-Induced Psychosis: an 18F-FDG PET/CT Case Study

Submitted15 June 2018. Accepted 13 December 2018. Epub ahead of print 13 February 2019Novel psychoactive substances (NPSs) have currently become a major public health concern because of relatively easy accessibility to these compounds and difficulty in identifying them with routine laboratory techniques. Here, we report the 18 F-fluorodeoxyglucose positron emission tomography/computerized tomography ( 18 F-FDG PET/CT) case study of a 23-year-old man who developed a substance-induced psychotic disorder after having intravenously injected himself with an unspecified amount of methoxetamine (MXE), a ketamine derivative hallucinogen. From a clinical perspective, a blunted affective responsiveness with diminished social drive and sense of purpose, along with a profound detachment from the environment, was observed. Psychometric and neuropsychological assessments highlighted severe dissociative symptoms and lack of motivation, along with a mild impairment of verbal fluency, working memory, and attention. Patient’s 18 F-FDG PET/CT scans displayed a significant bilateral deficit of tracer uptake within the dorsolateral prefrontal cortex (DLPFC). DLPFC activity is critical to goal-oriented cognitive functions, including working memory and sustained attention. DLPFC is also involved in both the temporal integration across multiple sensory modes and in the volitional control of actions, leading to the possibility to construct logically coherent temporal configurations of thought, speech, and behavior. This report highlights that a single acute MXE intoxication may produce severe brain impairment.Peer reviewedFinal Accepted Versio

Treatment of osteolytic solitary painful osseous metastases with radiofrequency ablation or cryoablation: a retrospective study by propensity analysis

The present study aimed to measure the improvement in pain relief and quality of life in patients with osteolytic solitary painful bone metastasis treated by cryoablation (CA) or radiofrequency ablation (RFA). Fifty patients with solitary osteolytic painful bone metastases were retrospectively studied and selected by propensity analysis. Twenty-five patients underwent CA and the remaining twenty-five underwent RFA. Pain relief, in terms of complete response (CR), the number of patients requiring analgesia and the changes in self-rated quality of life (QoL) were measured following the two treatments. Thirty-two percent of patients treated by CA experienced a CR at 12 weeks versus 20% of patients treated by RFA. The rate of CR increased significantly with respect to baseline only in the group treated by CA. In both groups there was a significant change in the partial response with respect to baseline (36% in the CA group vs. 44% in the RFA group). The recurrence rate in the CA and RFA groups was 12% and 8%, respectively. The reduction in narcotic medication requirements with respect to baseline was only significant in the group treated by CA. A significant improvement in self-rated QoL was observed in both groups. The present study seems to suggest that CA only significantly improves the rate of CR and decreases the requirement of narcotic medications. Both CA and RFA led to an improvement in the self-rated QoL of patients after the treatments. However, the results of the present study should be considered as preliminary and to serve as a framework around which future trials may be designed

Synthesis of Oligonucleotide Conjugates and Phosphorylated Nucleotide Analogues: An Improvement to a Solid Phase Synthetic Approach

An improvement to our solid phase strategy to generate pharmacologically interesting molecule libraries is proposed here. The synthesis of newo-chlorophenol-functionalised solid supports with very high loading (0.18–0.22 meq/g for control pore glass (CPG) and 0.25–0.50 meq/g for TG) is reported. To test the efficiency of these supports, we prepared nucleotide and oligonucleotide models, and their coupling yields and the purity of the crude detached materials were comparable to previously available results. These supports allow the facile and high-yield preparation of highly pure phosphodiester and phosphoramidate monoester nucleosides, conjugated oligonucleotides, and other yet unexplored classes of phosphodiester and phosphoramidate molecules

Combination of pharmacotherapy and lidocaine analgesic block of the peripheral trigeminal branches for trigeminal neuralgia: a pilot study

Classical trigeminal neuralgia (CTN) is treated predominantly by pharmacotherapy but side effects and unsuccessful occurs. The current study was carried out to evaluate the therapeutic effect of combination of pharmacotherapy and lidocaine block. Thirteen patients with CTN managed with pharmacotherapy were recruited and assigned either to no additional treatment (Group I) or to additional analgesic block (Group II). The primary endpoint was the reduction in the frequency of pain episodes in a month assessed at 30 and 90 days. Comparisons of measurements of pain, general health and depression scales were secondary endpoints. The results from the follow-up visits at 30 and 90 days showed the Group II to have larger reduction in the frequency of pain and exhibited a bigger improvement in the scores of the pain, general health and depression scales. The results from this preliminary study suggest a clinical benefit of the combination of pharmacotherapy and lidocaine block