Modeling Kelvin wave cascades in superfluid helium

We study two different types of simplified models for Kelvin wave turbulence on quantized vortex lines in superfluids near zero temperature. Our first model is obtained from a truncated expansion of the Local Induction Approximation (Truncated-LIA) and it is shown to possess the same scalings and the essential behaviour as the full Biot-Savart model, being much simpler than the later and, therefore, more amenable to theoretical and numerical investigations. The Truncated-LIA model supports six-wave interactions and dual cascades, which are clearly demonstrated via the direct numerical simulation of this model in the present paper. In particular, our simulations confirm presence of the weak turbulence regime and the theoretically predicted spectra for the direct energy cascade and the inverse wave action cascade. The second type of model we study, the Differential Approximation Model (DAM), takes a further drastic simplification by assuming locality of interactions in k-space via using a differential closure that preserves the main scalings of the Kelvin wave dynamics. DAMs are even more amenable to study and they form a useful tool by providing simple analytical solutions in the cases when extra physical effects are present, e.g. forcing by reconnections, friction dissipation and phonon radiation. We study these models numerically and test their theoretical predictions, in particular the formation of the stationary spectra, and closeness of numerics for the higher-order DAM to the analytical predictions for the lower-order DAM

COMPARZ Post Hoc Analysis: Characterizing Pazopanib Responders With Advanced Renal Cell Carcinoma

Background: The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ post hoc analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods: Patients were randomized to pazopanib 800 mg/d (n = 557) or sunitinib 50 mg/d, 4 weeks on/2 weeks off (n = 553). Secondary end points included time to complete response (CR)/partial response (PR); the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results: Median time to response was numerically shorter for patients treated with pazopanib versus sunitinib (11.9 vs. 17.4 weeks). Similar percentages of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). For patients without versus with adverse event (AE)-related dose reductions, median PFS, median overall survival, and ORR were 7.3 versus 12.5 months, 21.7 versus 36.8 months, and 22% versus 42% (all P <.0001) for pazopanib, and 5.5 versus 13.8 months, 18.1 versus 38.0 months, and 16% versus 34% (all P <.0001) for sunitinib; results were similar for dose interruptions. Conclusion: Dose modifications when required because of AEs were associated with improved efficacy, suggesting that AEs might be used as a surrogate marker of adequate dosing for individual patients

Safety and efficacy of Pazopanib in advanced soft tissue sarcoma: PALETTE (EORTC 62072) subgroup analyses.

Background PALETTE is a phase 3 trial that demonstrated single-agent activity of pazopanib in advanced soft tissue sarcomas (aSTS). We performed retrospective subgroup analyses to explore potential relationships between patient characteristics, prior lines of therapy, dose intensity, and dose modifications on safety and efficacy of pazopanib in aSTS.Methods PALETTE compared pazopanib with placebo in patients with aSTS (age ≥ 18 years) whose disease had progressed during or following prior chemotherapy. In these subgroup analyses, median progression-free survival (mPFS) among patients receiving pazopanib was the efficacy outcome of interest. Adverse events (AEs) were also compared within subgroups. All analyses were descriptive and exploratory.Results A total of 246 patients received pazopanib in the PALETTE study. The mPFS was longer in patients who had only 1 prior line versus 2+ prior lines of therapy (24.7 vs 18.9 weeks, respectively); AE rates were similar regardless of number of prior lines of therapy. The mPFS was similar in patients aged < 65 and ≥ 65 y (20.0 and 20.1 weeks, respectively). Although AEs leading to study discontinuation were higher in older patients (≥65 y, 30%; < 65 y, 17%), rates of dose reductions, dose interruptions, and serious AEs were similar between the 2 age groups. No reduction in mPFS was noted in patients requiring dose reductions or dose interruptions to manage toxicities.Conclusions Longer mPFS was observed in patients receiving pazopanib following only 1 line of therapy. Additionally, mPFS with pazopanib was maintained regardless of patient age or dose modifications used to manage toxicity.Trial registration NCT00753688 , first posted September 16, 2008 (registered prospectively)

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Putting the "landscape" in landscape genetics

Landscape genetics has emerged as a new research area that integrates population genetics, landscape ecology and spatial statistics. Researchers in this field can combine the high resolution of genetic markers with spatial data and a variety of statistical methods to evaluate the role that landscape variables play in shaping genetic diversity and population structure. While interest in this research area is growing rapidly, our ability to fully utilize landscape data, test explicit hypotheses and truly integrate these diverse disciplines has lagged behind. Part of the current challenge in the development of the field of landscape genetics is bridging the communication and knowledge gap between these highly specific and technical disciplines. The goal of this review is to help bridge this gap by exposing geneticists to terminology, sampling methods and analysis techniques widely used in landscape ecology and spatial statistics but rarely addressed in the genetics literature. We offer a definition for the term "landscape genetics", provide an overview of the landscape genetics literature, give guidelines for appropriate sampling design and useful analysis techniques, and discuss future directions in the field. We hope, this review will stimulate increased dialog and enhance interdisciplinary collaborations advancing this exciting new field

Le informazioni sul fair value degli strumenti finanziari e sulla gestione dei rischi finanziari (artt. 2427-bis e 2428, c.c.)

Il volume riporta il documento finale di lavoro elaborato dalla Commissione per i Principi Contabili istituita in seno al Consiglio Nazionale dei Dottori Commercialisti ed al Consiglio Nazionale dei Ragionieri e Periti Commerciali, avente per oggetto le linee guida per la corretta interpretazione delle informazioni sul fair value da riportare nella Nota Integrativa del bilanci

Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell Carcinoma

Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediate-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients. Results: Three hundred sixty three and 343 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS ≥ 2 (vs. PS &lt; 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar. Conclusions: Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (&lt; 2 vs. ≥ 2) to more accurately predict outcomes. © 2019 Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes. © 201

Temi economico-contabili

Il volume raccoglie i documenti elaborati dalla Commissione Nazionale per i Principi Contabili in materia di bilancio. Nello specifico, trattasi di linee guida per i problemi inerenti le informazioni in Nota Integrativa al bilancio, il consolidato fiscale nazionale e l'impairment tes