Optimal control of advertising and production of a seasonal product with nondifferentiable demand

We consider an application of optimal control theory to a marketing problem, in which a firm seeks the maximum profit by producing and selling a seasonal product. We assume that the firm can advertise its product in order to improve the firm goodwill and affect the product demand positively. In particular the demand is zero when the goodwill is less than a fixed threshold. The original optimal control problem is shown to be equivalent to a nonlinear programming problem, which has an optimal solution, possibly not unique

Discharge and suspended sediment flux estimated along the mainstream of the Amazon and the Madeira Rivers (from in situ and MODIS Satellite Data)

Water and suspended sediment fluxes are considered during the period 2000-2008 in a region including the full Amazon River from the confluence of the Negro River to Santarem, the end part of the Solimoes River, and the lower part of the Madeira River. Three types of data are used: water discharge estimated from field measurements, and suspended sediment obtained from field measurements and derived from MODIS satellite data. A generalized least square method including a propagating term is developed in order to propagate the signal upward and downward the river. The approach is introduced and tested. Several experiments are considered in order, first, to estimate the ability to propagate the signal from stations located before the confluences of Negro and Madeira Rivers to stations located on the Amazon River; second to investigate the possibility to propagate the signal along the Amazon River which dynamics is coupled with floodplains dynamics; and third to produce optimal solutions of water and sediment fluxes. For each experiment, the influence of field and satellite data is compared. The approach is efficient in the upper part of the region of study where the Solimoes, the Negro and the Madeira Rivers meet and fails in the lower part of the region where interactions between Amazon River and floodplains play an important role on the fluxes' dynamics. The optimal experiment includes in situ and satellite data from all the stations available and is used to analyse the recent evolution of suspended sediment flux along the Amazon River and its interaction with the large coupled floodplains. A high accumulation rate is observed during the 2000-2002 period, followed by decreasing rates until 2005 and by increasing values in 2006 and 2007. Our results suggest that floodplains extending along a river reach of 390 km-long between Itacoatiara and Obidos trap about 15% of the suspended sediment flux passing at Obidos. The simulated deposition rate is of about 0.3 Mt km(-1) yr(-1) corresponding to an accretion rate of about 27 mm yr(-1)

Mild Cryotherapy for Prevention of Paclitaxel-Induced Nail Toxicity in Breast Cancer Patients: A Phase II Single-Arm Clinical Trial

Background: Nail changes are among the most common dermatological adverse events in paclitaxel-receiving patients. Although effective, low-temperature prophylactic cryotherapy is discomforting and a potential cause of side effects, resulting in low patients’ adherence. Patients and Methods: A phase II single-arm study evaluating mild cryotherapy for the reduction of 12-week, grade 2 nail toxicity was conducted on 67 taxane-naïve breast cancer patients (age 18-74 years) undergoing weekly adjuvant chemotherapy with paclitaxel. Instant-ice packs were fixed over the fingers and toes for a total of 70 minutes during paclitaxel infusion at a temperature between -5 °C and +5 °C. Nail toxicity was evaluated weekly (CTCAE vs 4.03), including grade 2 (ie, onycholysis, subungual hematoma, onychomadesis) and grade 1 nail toxicities. Results: Twelve patients experienced grade 2 nail toxicities (17.9%, 95% confidence interval [CI] 9.6%-29.2%; median time to onset: 56 days): onycholysis was the most frequent grade 2 toxicity (13.4%), followed by subungual hematoma (9.0%) and onychomadesis (1.5%). Grade 1 toxicity occurred in 33 patients (63.5%, 95% CI 49.0%-76.4%) with nail discoloration representing by far the most frequent toxicity (59.6%). Seventeen patients (25.4%) reported no nail toxicity. 62.7% of patients reported no pain and 22.4% suffered moderate pain. No patient experienced severe pain or others adverse effects. Conclusions: Instant-ice pack is a feasible prophylactic intervention for nail toxicity, well tolerated by patients and with limited impact on routine workload. It could be considered for patients refusing (or interrupting) cryotherapy, and it can be implemented when frozen gloves management is not feasible

Il trapianto di cellule staminali emopoietiche: una revisione narrativa

. Haemopoietic stem cells transpantation: a narrative review. Haematopoietic stem cell transplantation (HSCT) is an effective treatment for many haematological malignancies and its employment is growing thanks to the increased possibility of finding suitable donors and the discovery of therapies to treat major complications. The fourth contribution on emergencies in the oncology setting proposes a narrative literature review to describe the transplant pathway, the types of HSCT, the conditioning regimen, the stem cells reinfusion, the aplasia phase, the major complications and the follow-up. The review included secondary studies published from 2020 to 2022, on adult transplanted patients and written in English; 30 studies were included. In addition, 28 primary studies describing key issues and 11 textbooks were added. Both autologous and allogeneic HSCT expose patients to infectious or drug therapy-related complications, such as mucositis and bleedings. The allogeneic HSCT is at higher risk of major complications such as the graft-versus-host disease and the venous-occlusive disease. The update proposed is accompanied by two cases with multiple choice questions, in patients who underwent autologous stem cells hematopoietic transplantation: case 1 (published in this issue of the AIR journal) on septic shock and case 2 (which will be published in the next issue of the AIR journal) on a massive hemothorax

Heart failure impairs the mechanotransduction properties of human cardiac pericytes

The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion. Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues. Results: Microvascular rarefaction and defects of YAP/TAZ activation characterize failing human hearts. Although both donor (D-) and explanted (E-) heart derived cardiac Pc support angiogenesis, D-Pc exert this effect significantly better than E-Pc. The latter are characterized by reduced focal adhesion density, decreased activation of the focal adhesion kinase (FAK)/ Crk-associated substrate (CAS) pathway, low expression of caveolin-1, and defective transduction of extracellular stiffness into cytoskeletal stiffening, together with an impaired response to both fibronectin and lysophosphatidic acid. Importantly, Mitogen-activated protein kinase kinase inhibition restores YAP/TAZ nuclear translocation. Conclusion: Heart failure impairs Pc mechano-transduction properties, but this defect could be reversed pharmacologically