A Nonparametric Conjugate Prior Distribution for the Maximizing Argument of a Noisy Function

We propose a novel Bayesian approach to solve stochastic optimization problems that involve finding extrema of noisy, nonlinear functions. Previous work has focused on representing possible functions explicitly, which leads to a two-step procedure of first, doing inference over the function space and second, finding the extrema of these functions. Here we skip the representation step and directly model the distribution over extrema. To this end, we devise a non-parametric conjugate prior based on a kernel regressor. The resulting posterior distribution directly captures the uncertainty over the maximum of the unknown function. We illustrate the effectiveness of our model by optimizing a noisy, high-dimensional, non-convex objective function.Comment: 9 pages, 5 figure

Orbital structure of the effective pairing interaction in the high-temperature superconducting cuprates

The nature of the effective interaction responsible for pairing in the high-temperature superconducting cuprates remains unsettled. This question has been studied extensively using the simplified single-band Hubbard model, which does not explicitly consider the orbital degrees of freedom of the relevant CuO$_2$ planes. Here, we use a dynamic cluster quantum Monte Carlo approximation to study the orbital structure of the pairing interaction in the three-band Hubbard model, which treats the orbital degrees of freedom explicitly. We find that the interaction predominately acts between neighboring copper orbitals, but with significant additional weight appearing on the surrounding bonding molecular oxygen orbitals. By explicitly comparing these results to those from the simpler single-band Hubbard model, our study provides strong support for the single-band framework for describing superconductivity in the cuprates

The Demand for Emerging Market Bonds

We study the multi-period asset allocation problem for emerging market investors whose asset menu consists of stocks, bonds and bills. We consider two types of emerging market investors: domestic investors (with returns in local currency) and international investors who can invest in US and emerging markets assets (with returns in US dollars). In developed markets, long-term government bonds are often considered attractive investment options for risk-averse investors. Our results show that emerging market bonds with a maturity of one year and longer can be attractive for domestic and international investors with different risk preferences, in both the short run and the long run

CFD analysis of the fuel-air mixture formation process in passive prechambers for use in a high-pressure direct injection (HPDI) Two-stroke engine

The research on two-stroke engines has been focused lately on the development of direct injection systems for reducing the emissions of hydrocarbons by minimizing the fuel shortcircuiting. Low temperature combustion (LTC) may be the next step to further improve emissions and fuel consumption; however, LTC requires unconventional ignition systems. Jet ignition, i.e., the use of prechambers to accelerate the combustion process, turned out to be an effective way to perform LTC. The present work aims at proving the feasibility of adopting passive prechambers in a high-pressure, direct injection, two-stroke engine through non-reactive computational fluid dynamics analyses. The goal of the analysis is the evaluation of the prechamber performance in terms of both scavenging efficiency of burnt gases and fuel/air mixture formation inside the prechamber volume itself, in order to guarantee the mixture ignitability. Two prechamber geometries, featuring different aspect ratios and orifice numbers, were investigated. The analyses were replicated for two different locations of the injection and for three operating conditions of the engine in terms of revolution speed and load. Upon examination of the results, the effectiveness of both prechambers was found to be strongly dependent on the injection setup

AB0462 BEHCET'S DISEASE: CLINICAL FEATURES AND OFF-LABEL BIOLOGIC TREATMENT STRATEGIES

Background:The treatment of Behçet's disease (BD) is still mainly based on the evidence derived from case reports, case series, retrospective analyses, and few clinical trials suggesting the safety and potential efficacy of off-label use of biologic agents in refractory cases.1Objectives:To describe clinical manifestations and their management, with particular focus on treatment indications, outcomes and safety of biologic therapy, in a cohort of patients with BD.Methods:Patients with a diagnosis of BD who visited our outpatient clinic until December 2019 were included in the study. Clinical data were recorded since diagnosis until the latest follow-up visit, analyzing clinical features, flares and therapeutic strategies adopted.Results:A total of 95 patients were included in the study with a medium follow-up of 108.54 ± 169.59 months. 20 of them (21. 05%) were treated with biologic agents. Patients treated with biologic therapy compared to those on conventional non-biologic therapies had a higher proportion of musculoskeletal (80% vs 46.67%, p = 0.008), neurological (30% vs 10.67%, p = 0.031), intestinal involvement (40% vs 12%, p = 0.004), and they were treated with a higher dose of glucocorticoids at diagnosis (16.84 mg ±14.01 vs 8.89 mg ± 11.76, p = 0.012). The most frequent indications for biologic step-up therapy were musculoskeletal involvement (40%), eye involvement (25%), neurological involvement (15%) and intestinal involvement (10%). Most patients initiated a biologic treatment within the first year of follow-up. TNF-inhibitor (TNFi) were more frequently prescribed (95%) and one patient was treated with 8 therapeutic cycles of Rituximab (500 mg/weekly for 4 infusions to be repeated after at least 6 months) because of recurrent pancytopenia. All patients experienced non-biologic therapy before starting a TNFi. The preferred first-line TNFi was infliximab (50%), followed by adalimumab (40%) and etanercept (5%). As second line treatment were also prescribed certolizumab (10%) and golimumab (5%). 10 patients switched to a second line treatment because of inefficacy of the first biologic agent, mainly because of refractory arthritis, intestinal and mucocutaneous involvement. One patient switched from infliximab to certolizumab during pregnancy with subsequent worsening of arthritis.85% of patients treated with biologic agents reached a clinical remission by the time of the latest follow up visit without any safety or tolerability issues.Conclusion:A relevant proportion of patients in our BD cohort were treated with biologic therapy, because of severe or refractory manifestations. The most frequent indications were musculoskeletal, neurological or intestinal involvement. Biologic agents were a generally effective and safe therapeutic approach.References:[1]F. Alibaz-Oner, M. H. Sawalha, H. Direskeneli. Management of Behçet disease, Curr. Opin. Rheumatol, 2018Table 1.General characteristics and disease involvement at diagnosisBiologic therapyNo biologic therapyp value20 (21.05%)75 (78.95%)General characteristicsMediaSDMediaSDAge at disease onset(years ± SD)34.5± 10.4938.64± 13.18p = 0.1976Diagnostic delay(months ± SD)45.28± 67.4828.09± 48.42p = 0.1996Glucocorticoids at diagnosis (mg prednisone ± SD)16.84± 14.018.89± 11.76p = 0.0115Glucocorticoids at latest follow up visit (mg prednisone ± SD)6.38± 7.763.83± 4.81p = 0.0707N%N%F / M12 / 860 / 4054 / 4172 / 28p = 0.3030Disease involvement at diagnosisOral ulcers2010075100Genital ulcers11553749,33p = 0.6540Cutaneous lesions15755066,67p = 0.4787Eye involvement6302736p = 0.6184Musculoskeletal involvement16803546,67p = 0.0082Neurological involvement630810,67p = 0.0311Intestinal involvement840912p = 0.0039Thrombosis2101824p = 0.1747Disclosure of Interests:None declare

Cytokine release syndrome after CAR infusion in pediatric patients with refractory/relapsed B-ALL: is there a role for diclofenac?

BACKGROUND: Cytokine release syndrome (CRS) is a major complication after chimeric-antigen receptor T-cell treatment, characterized by an uncontrolled systemic inflammatory reaction. We investigated the potential role of diclofenac in the management of CRS in five pediatric patients treated for relapsed/refractory B-lineage acute lymphoblastic leukemia. METHODS: In case of persistent fever with fever-free intervals shorter than 3 hours, diclofenac continuous infusion was initiated, at the starting dose of 0.5 mg/Kg/day, the lowest effective pediatric dose in our experience, possibly escalated up to 1 mg/Kg/day, as per institutional guidelines. RESULTS: CRS occurred at a median of 20 hours (range 8–27) after tisagenlecleucel infusion. Diclofenac was started at a median of 20 hours (range 13–33) after fever onset. A mean of 3.07 febrile peaks without diclofenac and 0.95 with diclofenac were reported (p = 0.02). Clinical benefit was achieved by hampering the progression of tachypnea and tachycardia. Despite fever control, CRS progressed in four of the five patients, and hypotension requiring vasopressors and fluid retention, as well as hypoxia, occurred. Vasopressors were followed by 1–2 doses of tocilizumab (one in patient 2 and two in patients 3, 4, and 5), plus steroids in patients 4 and 5. CONCLUSION: Based on a limited number of patients, diclofenac leads to better fever control, which translates into symptom relief and improvement of tachycardia, but could not prevent the progression of CRS

A phase II study of primary dose-dense sequential doxorubicin plus cyclophosphamide and docetaxel in cT4 breast cancer

Background: Dose-dense chemotherapy with anthracyclines and taxanes has improved either disease free survival or overall survival in high risk patients with early breast cancer. Patients and Methods: The activity and safety of a dose-dense schedule (q14 days) of adriamycin 60 mg/sqm and cyclophosphamide 600 mg/sqm (AC) x 4 cycles followed by docetaxel 75 mg/sqm for 4 cycles with hematopoietic support in patients with stage IIIB breast cancer was explored. Patients with ER >= 10% tumors received concomitant endocrine therapy with 3-month triptorelin and letrozole. Results: Fifteen patients with histologically proven cT4b (three patients) and cT4d (twelve patients) MO breast cancer were enrolled. Median age was 48 years (range 25-66). Eight clinical responses including one pathological complete remission (pCR), three stable disease (including minor responses) and four progression of disease, one during AC and three during taxotere, were observed. Four patients had grade 3-4 non hematological toxicities and all except one discontinued treatment. Conclusion: Due to the high rate of progressive disease, this schedule should not represent a standard option in cT4 breast cancer