On random flights with non-uniformly distributed directions

This paper deals with a new class of random flights $\underline{\bf X}_d(t),t>0,$ defined in the real space $\mathbb{R}^d, d\geq 2,$ characterized by non-uniform probability distributions on the multidimensional sphere. These random motions differ from similar models appeared in literature which take directions according to the uniform law. The family of angular probability distributions introduced in this paper depends on a parameter $\nu\geq 0$ which gives the level of drift of the motion. Furthermore, we assume that the number of changes of direction performed by the random flight is fixed. The time lengths between two consecutive changes of orientation have joint probability distribution given by a Dirichlet density function. The analysis of $\underline{\bf X}_d(t),t>0,$ is not an easy task, because it involves the calculation of integrals which are not always solvable. Therefore, we analyze the random flight $\underline{\bf X}_m^d(t),t>0,$ obtained as projection onto the lower spaces $\mathbb{R}^m,m<d,$ of the original random motion in $\mathbb{R}^d$. Then we get the probability distribution of $\underline{\bf X}_m^d(t),t>0.$ Although, in its general framework, the analysis of $\underline{\bf X}_d(t),t>0,$ is very complicated, for some values of $\nu$, we can provide some results on the process. Indeed, for $\nu=1$, we obtain the characteristic function of the random flight moving in $\mathbb{R}^d$. Furthermore, by inverting the characteristic function, we are able to give the analytic form (up to some constants) of the probability distribution of $\underline{\bf X}_d(t),t>0.$Comment: 28 pages, 3 figure

Individual calcium syntillas do not trigger spontaneous exocytosis from nerve terminals of the neurohypophysis

Recently, highly localized Ca(2+) release events, similar to Ca(2+) sparks in muscle, have been observed in neuronal preparations. Specifically, in murine neurohypophysial terminals (NHT), these events, termed Ca(2+) syntillas, emanate from a ryanodine-sensitive intracellular Ca(2+) pool and increase in frequency with depolarization in the absence of Ca(2+) influx. Despite such knowledge of the nature of these Ca(2+) release events, their physiological role in this system has yet to be defined. Such localized Ca(2+) release events, if they occur in the precise location of the final exocytotic event(s), may directly trigger exocytosis. However, directly addressing this hypothesis has not been possible, since no method capable of visualizing individual release events in these CNS terminals has been available. Here, we have adapted an amperometric method for studying vesicle fusion to this system which relies on loading the secretory granules with the false transmitter dopamine, thus allowing, for the first time, the recording of individual exocytotic events from peptidergic NHT. Simultaneous use of this technique along with high-speed Ca(2+) imaging has enabled us to establish that spontaneous neuropeptide release and Ca(2+) syntillas do not display any observable temporal or spatial correlation, confirming similar findings in chromaffin cells. Although these results indicate that syntillas do not play a direct role in eliciting spontaneous release, they do not rule out indirect modulatory effects of syntillas on secretion

High-resolution tracking in a GEM-Emulsion detector

SHiP (Search for Hidden Particles) is a beam dump experiment proposed at the CERN SPS aiming at the observation of long lived particles very weakly coupled with ordinary matter mostly produced in the decay of charmed hadrons. The beam dump facility of SHiP is also a copious factory of neutrinos of all three kinds and therefore a dedicated neutrino detector is foreseen in the SHiP apparatus. The neutrino detector exploits the Emulsion Cloud Chamber technique with a modular structure, alternating walls of target units and planes of electronic detectors providing the time stamp to the event. GEM detectors are one of the possible choices for this task. This paper reports the results of the first exposure to a muon beam at CERN of a new hybrid chamber, obtained by coupling a GEM chamber and an emulsion detector. Thanks to the micrometric accuracy of the emulsion detector, the position resolution of the GEM chamber as a function of the particle inclination was evaluated in two configurations, with and without the magnetic fiel

Can miRNAs be useful biomarkers in improving prognostic stratification in endometrial cancer patients? An update review

Endometrial cancer (EC) is the most common gynecological cancer, with annual incidence rates in Western countries ranging between 15 and 25 per 100 000 women. About 15% to 20% of patients with EC have high-risk disease and follow an aggressive clinical course. Unfortunately, the assessment of histologic parameters is poorly reproducible and conventional clinicopathological and molecular features do not reliably predict either the patient's response to the available treatments or the definition of personalized therapeutic approaches. In this context, the identification of novel diagnostic and prognostic biomarkers, which can be integrated in the current classification schemes, represents an unmet clinical need and an important challenge. miRNAs are key players in cancer by regulating the expression of specific target genes. Their role in EC, in association with clinical and prognostic tumor biomarkers, has been investigated but, so far, with little consensus among the studies. The present review aims to describe the recent advances in miRNAs research in EC taking into consideration the current classification schemes and to highlight the most promising miRNAs. Finally, a perspective point of view sheds light on the challenges ahead in the landscape of EC

Role of circulating mirnas in therapeutic response in epithelial ovarian cancer: A systematic revision

Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence

Large deviations for a damped telegraph process

In this paper we consider a slight generalization of the damped telegraph process in Di Crescenzo and Martinucci (2010). We prove a large deviation principle for this process and an asymptotic result for its level crossing probabilities (as the level goes to infinity). Finally we compare our results with the analogous well-known results for the standard telegraph process

Predictive role of MRI and18F FDG PET response to concurrent chemoradiation in T2B cervical cancer on clinical outcome: A retrospective single center study

Tumor response in locally advanced cervical cancer (LACC) is generally evaluated with MRI and PET, but this strategy is not supported by the literature. Therefore, we compared the diagnostic performance of these two techniques in the response evaluation to concurrent chemoradiotherapy (CCRT) in LACC. Patients with cervical cancer (CC) stage T2b treated with CCRT and submitted to MRI and PET/CT before and after treatment were enrolled in the study. All clinical, pathological, therapeutic, radiologic and follow-up data were collected and examined. The radiological response was analyzed and compared to the follow-up data. Data of 40 patients with LACC were analyzed. Agreement between MRI and PET/CT in the evaluation response to therapy was observed in 31/40 (77.5%) of cases. The agreement between MRI, PET/CT and follow-up data showed a Cohen kappa coefficient of 0.59 (95% CI = 0.267\u20130.913) and of 0.84 (95% CI = 0.636\u20131.00), respectively. Considering the evaluation of primary tumor response, PET/CT was correct in 97.5% of cases, and MRI in 92.5% of cases; no false negative cases were observed. These results suggest the use of PET/CT as a unique diagnostic imaging tool after CCRT, to correctly assess residual and progression disease

Quality of life with vulvar carcinoma treated with palliative electrochemotherapy: The elechtra (electrochemotherapy vulvar cancer) study

The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients’ outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p &lt; 0.0001). The FACT—V score improved significantly at early (9.6 ± 4.0) (p &lt; 0.0001) and late follow-up (8.9 ± 4.1) (p &lt; 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL