Nasopharyngeal carcinoma is a rare disease in Western countries. Nevertheless, its incidence in China, Singapore, and other Eastern countries reaches 20 cases per 100,000 people. Being an extremely ...chemo- and radiosensitive disease, upfront treatment often consists in the association of intensity-modulated radiation therapy and concurrent cisplatin. Unfortunately, about 20% of the patients suffer from a radioresistant disease which recurs after upfront therapy. For these patients, mainly available therapeutic options consist in systemic therapy, in particular poly-chemotherapy. In those showing a single locoregional recurrence, chemotherapy is not considered to be the preferred approach and other different strategies may be employed. Re-irradiation and surgery are strategies that are always used more often, albeit related to high risk of morbidity. Immunotherapy and targeted therapy, such as heavy ions-based re-irradiations, are experimental but very intriguing options.
IntroductionMixed depression (MxD), is a nosologic entity characterized by the presence of excitatory symptoms during a depressive episode. MxD embeds high levels of chronicity, functional impairment ...and suicidality. The assessment of MxD in a subpopulation that features high levels of fragility, such as oncology patients, represent a pivotal strategy to reduce illness burden and suicidality in these subjectsObjectivesThe aim of the present project is to assess the characteristics of MxD in oncology outpatients and to compare them with those of outpatients without oncological comorbidity.MethodsForty-two oncology outpatients with MxD (ONC-MxD); 34 oncology outpatients and inhibited depression (ONC-inhib); 187 outpatients with MxD without oncological comorbidity (MxD); 224 outpatients with inhibited depression without oncological comorbidity (Inhib) and 168 healthy controls (HC) have been recruited. Analyses made include comparisons of demographic and clinical variables, depression severity, excitatory symptoms, suicidality and functional impairment.ResultsOncology outpatients with depressive disorder showed greater severity of depressive symptoms and greater functional impairment than those without oncological comorbidity (F=187.08; p<.001; F=54.08; p<.001, respectively). ONC-inhib showed greater inhibition than Inhib (p<.001), whereas no differences in levels of excitatory symptoms are present between MxD e ONC-MxD (p=.159). ONC-DMX have a more recent diagnosis of cancer than ONC-inib (F=13.39, p<.001) and higher rates of suicidal ideation (χ²=11.89; p=.008).ConclusionsCancer might worsen depression severity, especially in its inhibitory component. Relationships between onset of cancer, excitatory symptoms and suicidality suggest that the period following the diagnosis of cancer is the one at higher risk for suicide. Strategies aiming to treat excitatory symptoms in such period might help reduce risk of suicide in oncology patients.Disclosure of InterestNone Declared
Abstract
Downsizing and turbocharging are nowadays widely spread techniques in automotive small-size internal combustion engines aimed at reducing the specific fuel consumption without affecting the ...power output. Due to the device small dimensions and to the high temperature of the exhaust-gases feeding the turbine, a relevant amount of heat is customarily exchanged between the turbine and the compressor so that a classical adiabatic approach could lead to an inaccurate estimation of the performance. This paper preliminary investigates the feasibility of an experimental procedure aimed at computing the exchanged work as variation of the angular momentum via a three-hole probe located at the impeller outlet. Because of the very reduced machine dimensions, torque measurements could be difficult, as the intrusive nature of the measurement could significantly affect the accuracy of the collected data. For this reason, the influence of the probe finite-size onto the flow field is numerically analysed solving the Unsteady Reynolds-Averaged Navier Stokes equations with and without the probe installed at the diffuser inlet. The equations are closed via the
k
−
ω
SST turbulence model, while a density-based commercial CFD package is used to integrate the governing equation. Finally, the pressure distribution in the azimuthal direction is analysed to assess the probe intrusive effects which, in the proposed case, result in a 0.47% (resp. 0.69%) difference in the specific work when a miniaturized probe with a diameter of 1mm (resp. 1.5 mm) is employed.
Abstract Introduction The optimal extent of the groin lymph node (LN) dissection for melanoma patients with positive sentinel LN biopsy is still debated and no agreement exist on dissection of pelvic ...LN. This study aimed at investigating predictors of pelvic LN metastasis and prognostic significance of having metastasis in the pelvic LNs. Methods Clinicopathologic data of 740 patients with positive groin sentinel LN who underwent ilioinguinal completion LN dissection at four Italian centre were analysed. Multivariable logistic and Cox regression analysis was used to identify independent predictors of pelvic LN metastasis and to adjust prognostic significance of pelvic LN metastasis. Results More than a quarter (26%) of patients had positive non-SLNs after inguinal and pelvic lymphadenectomy, which were located in their pelvis in the 12% of cases. Older patients (OR) 1.69; 95% confidence interval (CI) 1.02–2.78 having thick primary (OR 1.6; 95% CI, 1.01–2.53) and ≥ 2 positive SLNs (OR 2.5; 95% CI, 1.4–4.47) were more likely to harbour pelvic LN metastasis. Interestingly, 4% of all patients (34% of patients with positive pelvic LNs) had pelvic LN metastasis with negative inguinal LNs. Pelvic LN metastasis was independently associated with higher risk of recurrence and lower survival. 5-year disease free and overall survival was 30% and 50%, respectively, for patients with pelvic LN metastasis. Conclusions Pelvic LNs are frequently positive after ilioinguinal lymphadenectomy and it should be considered for all patients, especially those who are older, have thick primary and ≥ 2 positive SLN. Patients with pelvic LN metastasis have worse prognosis.
3,4-Dichloro-N-benzamide (AH-7921) is a cyclohexyl-methylbenzamide derivative with analgesic activity, whose abuse was associated with several fatal intoxications, included in Schedule I of UN Single ...Convention on Narcotic Drugs. We validated an HPLC-MS/MS method to investigate its brain disposition and metabolism after single and repeated injections; in parallel, we evaluated its central behavioral effects.
After an intraperitoneal injection of 10 mg/kg, the analgesic effect appeared after 5 min and persisted up to 4 h; brain absorption was rapid (tmax 30 min) and large (brain-to-plasma ratio 16), with active concentration >700 ng/g. By high-resolution MS we identified several metabolites in plasma and brain, the most important being N-demethylated and N,N-didemethylated metabolites; they showed high brain permeability, although they probably do not contribute to the analgesic effect of the parent compound (brain tmax>2 h). Starting 2 h after treatment, the two metabolites showed higher plasma and brain concentrations than the parent molecule, which persisted much longer, and could be used to evaluate drug intake in human consumers.
Tolerance was observed after seven daily doses, when the compound's analgesic effect was 14% lower than after the first dose; since brain concentrations did not decrease in parallel, the development of pharmacodynamic tolerance can be suggested. However, pharmacokinetic tolerance is also likely, as brought to light by the data after a dose challenge, given after a 48 h washout period from the 7th dose, showing a lower brain-to-plasma ratio. We also describe the rewarding effect of AH-7921 (conditioned place preference), suggesting a high risk of addiction in humans.
•Method to measure the narcotic drug AH-7921 and its metabolites in plasma and brain.•The analgesic effect depends on brain levels of AH-7921 but not of metabolites.•Main metabolites are slowly cleared and can be used to assess drug intake in humans.•Repeated treatment results in both PD and PK tolerance to the analgesic affect.•AH-7921 has positive motivational properties.
-Methyl-4-methylaminorex (4,4'-DMAR) is a phenethylamine derivative with psychostimulant activity whose abuse has been associated with several deaths and a wide range of adverse effects. We recently ...validated a high-performance liquid chromatography-tandem mass spectrometry method to measure the compound's concentrations in plasma, and we applied it to describe the pharmacokinetic properties of 4,4'-DMAR after a single dose in rats. In this study, we investigated the brain disposition and metabolism of
4,4'-DMAR after intraperitoneal injection as well as its central behavioral effects. Locomotor activity increased after a single injection of 10 mg/kg, peaking at 2 hours and disappearing at 5 hours; in these conditions, brain absorption was very rapid, (
= 30-60 minutes) and large (brain-to-plasma ratio = 24); the half-life was approximately 50 minutes. After 14 daily doses, the compound's effect on locomotor activity was greater (approximately 20% compared with the effect after the first dose), but not for pharmacokinetic reasons. Using high-resolution mass spectrometry, we also identified four metabolites of
4,4'-DMAR in the plasma and brain of treated rats. Semiquantitative analysis indicated low brain permeability and very low brain concentrations, suggesting that these metabolites do not contribute to central behavioral effects; however, the metabolite originating from oxidation of the
-methyl group (M2) persisted in the plasma longer and at higher concentrations than the parent molecule and could be used to evaluate drug intake in human consumers. Finally, we describe the rewarding effect of
-4,4'-DMAR in the conditioning place preference test, suggesting a high risk of addiction in humans.
The study investigates the soundness of a popular uncoupled design strategy for diffuser-augmented wind turbines (DAWTs), namely the use of an annular wing to enclose an existing open-rotor. To this ...aim, the paper presents a numerical analysis of the NREL-Phase-VI rotor enclosed into a shroud whose cross-section consists of the Selig-S1223 airfoil. Particular attention is devoted to the analysis of the blade pressure fields, velocity triangles, blade forces, tip-vortex and wake development. The data show that the duct induces a gain in the rotor inlet axial velocity and, therefore, in the local flow-angle. Consequently, the blade forces, the extracted work, and the risk of flow separation considerably rise. Thanks to the simultaneous increase in the ingested mass flow rate and extracted work, the DAWT experiences a higher power coefficient (CP,exit) which, however, would be further improved if a coupled design-procedure was used. Indeed, in the present case, the maximum CP,exit is obtained for the wind-speed value corresponding to the duct optimal flow behaviour. However, in this condition, the rotor operates at off-design with an extensive flow-separation on the blade suction-side. Finally, while the inefficiencies magnitude is specific of the analysed case, the conceptual relevance of the achievements remains valid in general.
•Can efficient DWTs be designed ducting an existing open rotor?•Blade-resolved analysis of the NREL PhaseVI rotor enclosed in a Selig S1223 airfoil.•Ducting the rotor, the blade forces, the work, and the risk of flow separation rise.•The DWT has a higher CP,ex (0.48, gain: 21.66%) which is, however, lower than 0.59.•The study reveals the uncoupled design flaws yielding not-optimal flow conditions.
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