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Background: Information about the adherence to scientific societies guidelines in the ‘real-world’ therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). Patients and methods: Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. Results: Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years; 24% >75 years); 48% were female; 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1; group A: 16%, group B: 30%; group C: 54%; 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% [95% confidence interval (CI) 59% to 76%]; 53% of patients received gemcitabine and 15% gemcitabine þ capecitabine; median CA19.9 was 29 (range 0-7300; not reported 15%); median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%); 55% of patients received nab-paclitaxel þ gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial; median CA19.9 was 337 (range 0-20220; not reported 9%); median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%); 71% of patients received nabpaclitaxel þ gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial; liver and lung metastases were reported in 76% and 23% of patients, respectively; median CA19.9 value was 760 (range 0-1374500; not reported 9%); median survival was 10.0 months (95% CI 9.1-11.1 months). Conclusions: The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced; nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

Background Limited information is available on the relevant prognostic variables after surgery for patients with pancreatic ductal adenocarcinoma (PDAC) subjected to neoadjuvant chemotherapy (NACT). NACT is known to induce a spectrum of histological changes in PDAC. Different grading regression systems are currently available; unfortunately, they lack precision and accuracy. We aimed to identify a new quantitative prognostic index based on tumor morphology. Patients and Methods The study population was composed of 69 patients with resectable or borderline resectable PDAC treated with preoperative NACT (neoadjuvant group) and 36 patients submitted to upfront surgery (upfront-surgery group). A comprehensive histological assessment on hematoxylin and eosin (H&E) stained sections evaluated 20 morphological parameters. The association between patient survival and morphological variables was evaluated to generate a prognostic index. Results The distribution of morphological parameters evaluated was significantly different between upfront-surgery and neoadjuvant groups, demonstrating the effect of NACT on tumor morphology. On multivariate analysis for patients that received NACT, the predictors of shorter overall survival (OS) and disease-free survival (DFS) were perineural invasion and lymph node ratio. Conversely, high stroma to neoplasia ratio predicted longer OS and DFS. These variables were combined to generate a semiquantitative prognostic index based on both OS and DFS, which significantly distinguished patients with poor outcomes from those with a good outcome. Bootstrap analysis confirmed the reproducibility of the model. Conclusions The pathologic prognostic index proposed is mostly quantitative in nature, easy to use, and may represent a reliable tumor regression grading system to predict patient outcomes after NACT followed by surgery for PDAC.

Cloud computing is a novel raising computing resource allocation. Successful development of cloud computing paradigm necessitates explicit performance evaluation of cloud data centers. The computing resource allocation and performance managing have been one of the most important septets of cloud computing. In this paper, we consider the cloud center as a queuing system with single task arrivals and a task request buffer of infinite capacity. We assess the performance of queuing system by using an analytical model and solve it to obtain important performance factors like mean number of tasks in the system. Using this model in order to evaluate the performance analysis of cloud server farms and obtained solved it to obtain accurate estimation of complete probability distribution of the request response time and other paramount performance indicators.

In this paper, we study the oscillatory behavior of the fractional difference equations of the following form for 0 1, t0  t  0,    denotes the Riemann-Liouville difference operator and  0 is a quotient of odd positive integers. We establish some oscillation criteria for the equation by using Riccati transformation technique and some inequalities. An example is shown to illustrate our main results.

In this paper we investigate of multi-server retrial queue system .Server provides two stages of homogeneous service in succession. The customer has to complete first service from first server then to the second server of the service. After completion of the second service, the second server takes Bernoulli vacation. On arriving customer on finding a free for the first server enters into service immediately, and goes for the second server; otherwise the customer enters into an orbit of infinite service. An orbiting customer competes for the service by sending signals at random times until a free server is captured. Using the above concept we obtain steady state behaviour of multiserver.

Pneumonia merupakan penyebab utama kesakitan dan kematian pada anak, terutama di negara berkembang. Angka kematian karena pneumonia di negara berkembang 10–15 kali lebih tinggi daripada di negara maju. Penelitian ini bertujuan untuk mengetahui angka kematian dan faktor risiko pada anak balita yang dirawat di rumah sakit karena pneumonia. Penelitian potong lintang ini dilakukan pada anak usia 1–59 bulan yang dirawat di Rumah Sakit Dr. Hasan Sadikin Bandung karena pneumonia periode November 2007─Januari 2009. Tiga ratus delapan belas anak ikut serta dalam penelitian ini. Usia median anak 11‚6 bulan, sebanyak 237 (74‚5%) di antaranya berusia ≤12 bulan. Sembilan puluh tiga (29‚2%) anak didiagnosis pneumonia sangat berat dan 225 (70‚8%) anak pneumonia berat. Dua puluh tiga (7‚2%) penderita meninggal selama perawatan, 20 di antaranya dirawat dengan pneumonia sangat berat (p

We analyze stochastic integrals associated with a mutation process. To be specific, we describe the cell population process and derive the differential equations for the joint generating functions for the number of mutants and their integrals in generating functions and their applications. We obtain first-order moments of the processes of the two-way mutation process in first-order moment structure of X (t) and Y (t) and the second-order moments of a one-way mutation process. In this paper, we obtain the limiting behaviour of the integrals in limiting distributions of X (t) and Y (t)., {"references":["Anderson, W. J. (1991). \"Continuous-Time Markov Chains: An Applications-Oriented Approach\". Springer, New York.","Brockwell, P. J. (1985). \"The extinction time of a birth, death and catastrophe process and of a related diffusion model\". Adv. Appl. Prob. 17, 42-52.","Brockwell, P. J., Gani, J. And Resnick, S. I. (1982). \"Birth, immigration and catastrophe processes\". Adv. Appl. Prob. 14, 709-731.","Chen, A., Pollett, P. K., Zhang, H. And Cairns, B. (2003).\"Uniqueness Criteria for continuous-time Markov chains with general transition structure\". Submitted. Available.","Ezhov, I. I. And Reshetnyak, V. N. (1983). \"Amodification of the branching process\".Ukranian Math. J. 35, 28-33.","Harris, T. E. (1963). \"The Theory of Branching Processes\". Springer, Berlin.intermaths.","Krishna Kumar, B.; Arivudainambi, D. \"Transient solution of an M/M/1 queue with catastrophes. Comput. Math. Appl. 2000, 40, 1233–1240.","Mangel, M. And Tier, C. (1993). \"Dynamics of meta populations with demographic stochasticity and environmental catastrophes\". Theoret. Pop. Biol. 44, 1-31.","Pakes, A. G. (1987). \"Limit theorems for the population size of a birth and death process allowing catastrophes\". J. Math. Biol. 25, 307-325.\n[10]\tPakes, A. G. (1989). \"Asymptotic results for the extinction time of Markov branching processes allowing emigration\". I. Random walk decrements. Adv. Appl. Prob. 21, 243-269."]}

Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.

From January 1981 to December 1987, 264 patients affected with small breast cancers were treated with quadrantectomy plus axillary dissection and radiation therapy on the breast remnant (QUART). Mean age of the patients was 53 years; 124 of them were less than or equal to 50 years old (46.9%); 85 had axillary nodal metastases (32.2%), and 58 presented a primary tumor with pathologic size (greater than 2 cm) (22.9%). Overall actuarial survival at 3 and 7 years, according to the Kaplan and Meyer method, was 95.5% and 85.3%, respectively; NED survival was 85.9% and 77.4%. Twenty patients died (19 of cancer). Local relapses were 6 (2.3% on the whole and 13.3% on the whole of recurrences observed at follow-up). Local relapses were central in the quadrantectomy scar in 4/6 patients. Histology and site of the primary lesion were not correlated with a major risk of local failure. Isolated recurrences in the breast did not worsen survival. Nodal failures were 5 (1.9% on the whole of cases; 11.1% on the whole of failures). Our study confirms the role of QUART as an effective and reliable method in the treatment of small breast carcinomas.

We report on 49 patients with pathologic stage I endometrial adenocarcinoma who underwent postoperative whole-pelvis irradiation (RT) (45-50 Gy in 5-6 weeks) from November 1981 to December 1988. RT was performed when one or more of the following unfavorable prognostic factors were discovered: myometrial infiltration greater than 1/3 (42 cases, or 85.7%), poorly-differentiated tumor (10, or 20.4%), tubaric angles involvement (4; or 8.2%), pelvic nodal metastases (1, or 2.0%). Five-year actuarial disease-free survival was 91.4%. After an average follow-up of 58 months, we observed recurrent disease in 4 patients (8.2%) (3 cases with distant metastases, 6.1%; 1 case with vaginal relapse, 2.0%). All recurrences were observed within 18 months from treatment and occurred only in patients with both myometrial infiltration greater than 1/3 and poorly or moderately differentiated tumor. The patient with vaginal relapse had a complete response after endocavitary curietherapy, but died later on from lung metastases. None of the treated patients experienced severe complications related to the treatment. Our results are comparable with those of the most recent literature, and confirm the good tolerance and efficacy of postoperative RT to prevent loco-regional relapses in early stage endometrial cancer with unfavorable prognostic factors.

Objective Germline BRCA1-2 pathogenic variants (gBRCApv) increase the risk of pancreatic cancer and predict for response to platinating agents and poly(ADP-ribose) polymerase inhibitors. Data on worldwide gBRCApv incidence among pancreatic ductal adenocarcinoma (PDAC) patients are sparse and describe a remarkable geographic heterogeneity. The aim of this study is to analyze the epidemiology of gBRCApv in Italian patients. Materials and methods Patients of any age with pancreatic adenocarcinoma, screened within 3 months from diagnosis for gBRCApv in Italian oncologic centers systematically performing tests without any selection. For the purposes of our analysis, breast, ovarian, pancreas, and prostate cancer in a patient's family history was considered as potentially BRCA-associated. Patients or disease characteristics were examined using the χ2 test or Fisher's exact test for qualitative variables and the Student's t-test or Mann–Whitney test for continuous variables, as appropriate. Results Between June 2015 and May 2020, 939 patients were tested by 14 Italian centers; 492 (52%) males, median age 62 years (range 28-87), 569 (61%) metastatic, 273 (29%) with a family history of potentially BRCA-associated cancers. gBRCA1-2pv were found in 76 patients (8.1%; 9.1% in metastatic; 6.4% in non-metastatic). The gBRCA2/gBRCA1 ratio was 5.4 : 1. Patients with gBRCApv were younger compared with wild-type (59 versus 62 years, P = 0.01). The gBRCApv rate was 17.1% among patients 70 years old (none out of 94 patients >73 years old). gBRCApv frequency in 845 patients, Highlights • This is the largest case series of incident PDAC patients screened for germline BRCA1-2 pathologic variants (gBRCApv). • The incidence of gBRCA1-2pv was 8.1% in the whole population; 9.1% in metastatic patients; 6.4% in non-metastatic patients. • No gBRCA1-2pv was observed over the age of 73. • These data suggest screening all PDAC patients

Studies regarding the radiobiological effects of low dose radiation, microbeam irradiation services have been developed in the world and today laser acceleration of protons and heavy ions may be used in radiation therapy. The application of different facilities is essential for studying bystander effects and relating signalling phenomena in different cells or tissues. In particular the use of ion beams results advantageous in cancer radiotherapy compared to more commonly used X-rays, since the ability of ions in delivering lethal amount of doses into the target tumour avoiding or limiting damage to the contiguous healthy tissues. At the INFN-LNS in Catania, a multidisciplinary radiobiology group is strategically structured aimed to develop radiobiological research, finalised to therapeutic applications, compatible with the use of high dose laser-driven ion beams. The characteristic non-continuous dose rates with several orders of magnitude of laser-driven ion beams makes this facility very interesting in the cellular systems' response to ultra-high dose rates with non-conventional pulse time intervals cellular studies. Our group have projected to examine the effect of high dose laser-driven ion beams on two cellular types: foetal fibroblasts (normal control cells) and DU145 (prostate cancer cells), studying the modulation of some different bio-molecular parameters, in particular cell proliferation and viability, DNA damage, redox cellular status, morphological alterations of both the cytoskeleton components and some cell organelles and the possible presence of apoptotic or necrotic cell death. Our group performed preliminary experiments with high energy (60 MeV), dose rate of 10 Gy/min, doses of 1, 2, 3 Gy and LET 1 keV/mu m on human foetal fibroblasts (control cells). We observed that cell viability was not influenced by the characteristics of the beam, the irradiation conditions or the analysis time. Conversely, DNA damage was present at time 0, immediately following irradiation in a dose-dependent manner. The analysis of repair capability showed that the cells irradiated with 1 and 2 Gy almost completely recovered from the damage, but not, however, 3 Gy treated cells in which DNA damage was not recovered. In addition, the results indicate the importance of the use of an appropriate control in radiobiological in vitro analysis.

Bacopa monniera L. (family Scrophulariaceae) (BM) is an Ayurvedic medicine, clinically used for memory enhancing, epilepsy, insomnia and as a mild sedative. In this work, the free radical scavenging capacity of a methanol extract of BM and the effect on DNA cleavage induced by H2O2 UV-photolysis was investigated. In addition, we examined whether this plant extract is capable of reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human non-immortalized fibroblasts. It showed a dose-dependent free radical scavenging capacity and a protective effect on DNA cleavage. These results were confirmed by a significant protective effect on H2O2 - induced cytoxicity and DNA damage in human non-immortalized fibroblasts. The antioxidant capacity of BM may explain, at least in part, the reported antistress, immunomodulatory, cognition-facilitating, antiinflammatory and antiaging effects produced by it in experimental animals and in clinical situations and may justify further investigation of its other beneficial properties. Moreover, this experimental evidence suggests that because of its antioxidant activity, this Ayurvedic drug may be useful in the treatment of human pathologies in which free radical production plays a key role. Copyright (C) 2003 John Wiley Sons, Ltd.

By classical results, a compact Riemann surface, or equivalently an orientable closed hyperbolic 2-manifold, has at most one hyperelliptic involution (i.e. the quotient by the involution is the 2-sphere). A hyperelliptic involution is central in the automorphism or isometry group of such a hyperelliptic surface, its fixed points are exactly the Weierstrass points of the surface (see e.g. [FK]). In the present paper, we consider hyperelliptic involutions of hyperbolic 3manifolds; by definition, these are isometric involutions whose quotient is the 3-sphere. The situation is more complicated in dimension three, in particular a hyperbolic 3-manifold can have more than one hyperelliptic involution. Our main result states that there is a universal bound on the number of non-conjugate hyperelliptic involutions of closed hyperbolic 3-manifolds; this bound is quite small, and we compute it for various situations. Our methods also determine how different hyperelliptic involutions are related. There remains a small gap between these upper bounds and the number of different involutionswhichwe can actually construct (see [R1],[RZ]).We remark that the question on the number of different hyperelliptic involutions of hyperbolic 3-manifolds has explicitly been asked in [MV]. We obtain also results for hyperelliptic isometries of orders greater than two; in particular, for prime numbers p > 2, we give a complete solution to the problem on the number of different hyperelliptic isometries of order p (i.e. the upper bound we obtain is sharp). Let Isom+(M) denote the orientation preserving isometry group of a hyperbolic 3-manifoldM .