Bayesian Model Selection for Beta Autoregressive Processes

We deal with Bayesian inference for Beta autoregressive processes. We restrict our attention to the class of conditionally linear processes. These processes are particularly suitable for forecasting purposes, but are difficult to estimate due to the constraints on the parameter space. We provide a full Bayesian approach to the estimation and include the parameter restrictions in the inference problem by a suitable specification of the prior distributions. Moreover in a Bayesian framework parameter estimation and model choice can be solved simultaneously. In particular we suggest a Markov-Chain Monte Carlo (MCMC) procedure based on a Metropolis-Hastings within Gibbs algorithm and solve the model selection problem following a reversible jump MCMC approach

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Intratumor Regulatory Noncytotoxic NK Cells in Patients with Hepatocellular Carcinoma

Previous studies support the role of natural killer (NK) cells in controlling hepatocellular carcinoma (HCC) progression. However, ambiguity remains about the multiplicity and the role of different NK cell subsets, as a pro-oncogenic function has been suggested. We performed phenotypic and functional characterization of NK cells infiltrating HCC, with the corresponding nontumorous tissue and liver from patients undergoing liver resection for colorectal liver metastasis used as controls. We identified a reduced number of NK cells in tumors with higher frequency of CD56(BRIGHT)CD16(-) NK cells associated with higher expression of NKG2A, NKp44, and NKp30 and downregulation of NKG2D. Liver-resident (CXCR6(+)) NK cells were reduced in the tumors where T-bet(hi)Eomes(lo) expression was predominant. HCCs showed higher expression of CD49a with particular enrichment in CD49a(+)Eomes(+) NK cells, a subset typically represented in the decidua and playing a proangiogenic function. Functional analysis showed reduced TNF-alpha production along with impaired cytotoxic capacity that was inversely related to CXCR6(-), T-bet(hi)Eomes(lo), and CD49a(+)Eomes(+) NK cells. In conclusion, we identified a subset of NK cells infiltrating HCC, including non-liver-resident cells that coexpressed CD49a and Eomes and showed reduced cytotoxic potential. This NK cell subset likely plays a regulatory role in proangiogenic function

Sub-surface modifications in silicon with ultra-short pulsed lasers above 2 µm

Nonlinear optical phenomena in silicon such as self-focusing and multi-photon absorption are strongly dependent on the wavelength, energy, and duration of the exciting pulse, especially for wavelengths >2µm. We investigate the sub-surface modification of silicon using ultra-short pulsed lasers at wavelengths in the range of 1950–2400 nm, at a pulse duration between 2 and 10 ps and pulse energy varying from 1 µJ to 1 mJ. We perform numerical simulations and experiments using fiber-based lasers built in-house that operate in this wavelength range for the surface and sub-surface processing of Si-wafers. The results are compared to the literature data at 1550 nm. Due to a dip in the nonlinear absorption spectrum and a peak in the spectrum of the third-order nonlinearity, the wavelengths between 2000 and 2200 nm prove to be more favorable for creating sub-surface modifications in silicon. This is the case even though those wavelengths do not allow as tight focusing as those at 1550 nm. This is compensated for by an increased self-focusing due to the nonlinear Kerr-effect around 2100 nm at high light intensities, characteristic for ultra-short pulses

The late Pleistocene Po River lowstand wedge in the Adriatic Sea : Controls on architecture variability and sediment partitioning

The authors dedicate this study to their colleague Giovanni Bortoluzzi, who passed away in 2015. A special tanks is due to Marco Ligi and Nevio Zitellini for geophysical data acquisition and processing; Marco Pastore and Filippo D'Oriano for their support during the cruise LSD2014 and processing of geophysical data. Elisabetta Campiani provided additional support for processing the multibeam bathymetry. A particular thank goes to Cpt. Emanuele Gentile and the crew of the R/V Urania during cruise LSD 2014. We thank Ronald Steel and an anonymous Reviewer for their constructive comments. This project was funded by ExxonMobil Upstream Research Company and by the Flagship Project RITMARE–The Italian Research for the Sea. We acknowledge the European Union Project PROMESS-1 (contract EVR1-2001-41) for borehole PRAD 1-2. This is ISMAR-CNR contribution number 1959.Peer reviewedPostprin

A novel DSP zebrafish model reveals training- and drug-induced modulation of arrhythmogenic cardiomyopathy phenotypes

Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested. Our stable Dsp knock-out (KO) zebrafish line was characterized by cardiac alterations, oedema and bradycardia at larval stages. Histological analysis of mutated adult hearts showed reduced contractile structures and abnormal shape of the ventricle, with thinning of the myocardial layer, vessels dilation and presence of adipocytes within the myocardium. Moreover, TEM analysis revealed “pale”, disorganized and delocalized desmosomes. Intensive physical training protocol caused a global worsening of the cardiac phenotype, accelerating the progression of the disease. Of note, we detected a decrease of Wnt/β-catenin signalling, recently associated with AC pathogenesis, as well as Hippo/YAP-TAZ and TGF-β pathway dysregulation. Pharmacological treatment of mutated larvae with SB216763, a Wnt/β-catenin agonist, rescued pathway expression and cardiac abnormalities, stabilizing the heart rhythm. Overall, our Dsp KO zebrafish line recapitulates many AC features observed in human patients, pointing at zebrafish as a suitable system for in vivo analysis of environmental modulators, such as the physical exercise, and the screening of pathway-targeted drugs, especially related to the Wnt/β-catenin signalling cascade

Efficient clofilium tosylate-mediated rescue of POLG-related disease phenotypes in zebrafish

The DNA polymerase gamma (Polg) is a nuclear-encoded enzyme involved in DNA replication in animal mitochondria. In humans, mutations in the POLG gene underlie a set of mitochondrial diseases characterized by mitochondrial DNA (mtDNA) depletion or deletion and multiorgan defects, named POLG disorders, for which an effective therapy is still needed. By applying antisense strategies, ENU- and CRISPR/Cas9-based mutagenesis, we have generated embryonic, larval-lethal and adult-viable zebrafish Polg models. Morphological and functional characterizations detected a set of phenotypes remarkably associated to POLG disorders, including cardiac, skeletal muscle, hepatic and gonadal defects, as well as mitochondrial dysfunctions and, notably, a perturbed mitochondria-to-nucleus retrograde signaling (CREB and Hypoxia pathways). Next, taking advantage of preliminary evidence on the candidate molecule Clofilium tosylate (CLO), we tested CLO toxicity and then its efficacy in our zebrafish lines. Interestingly, at well tolerated doses, the CLO drug could successfully rescue mtDNA and Complex I respiratory activity to normal levels, even in mutant phenotypes worsened by treatment with Ethidium Bromide. In addition, the CLO drug could efficiently restore cardio-skeletal parameters and mitochondrial mass back to normal values. Altogether, these evidences point to zebrafish as a valuable vertebrate organism to faithfully phenocopy multiple defects detected in POLG patients. Moreover, this model represents an excellent platform to screen, at the whole-animal level, candidate molecules with therapeutic effects in POLG disorders

Resection of metachronous pancreatic cancer 4 years after pancreaticoduodenectomy for stage III pancreatic adenocarcinoma

Pancreatic adenocarcinoma frequently recurs in patients even after resection with curative intent. The majority of these are early recurrences and are associated with metastatic disease, thus not amenable to repeat resection. Here we report a patient who underwent completion pancreatectomy for a metachronous pancreatic adenocarcinoma. This patient initially presented with painless jaundice and computed tomography (CT) revealed a mass in the head of the pancreas. Brushings obtained at endoscopic retrograde cholangiopancreatography (ERCP) were positive for adenocarcinoma. This patient then underwent a Whipple procedure and final pathology demonstrated stage III pancreatic ductal adenocarcinoma. Adjuvant therapy included gemcitabine and erlotinib. This patient was followed with physical examinations and serial laboratory and imaging studies. There was no evidence of disease for four years at which time and sharp elevation in CA-19-9 was found. Subsequent imaging revealed a mass in the remnant pancreas. Curative intent completion pancreatectomy was then performed which confirmed the presence of pancreatic adenocarcinoma. This was followed by adjuvant Gemcitabine based chemotherapy and chemoradiation. One year later the patient is alive with no evidence of disease. Thus, in highly selected patients with recurrent or metachronous pancreatic cancer, repeat pancreatectomy can be considered, but the course of treatment should be considered in a multidisciplinary setting