Quantile hidden semi-Markov models for multivariate time series

This paper develops a quantile hidden semi-Markov regression to jointly estimate multiple quantiles for the analysis of multivariate time series. The approach is based upon the Multivariate Asymmetric Laplace (MAL) distribution, which allows to model the quantiles of all univariate conditional distributions of a multivariate response simultaneously, incorporating the correlation structure among the outcomes. Unobserved serial heterogeneity across observations is modeled by introducing regime-dependent parameters that evolve according to a latent finite-state semi-Markov chain. Exploiting the hierarchical representation of the MAL, inference is carried out using an efficient Expectation-Maximization algorithm based on closed form updates for all model parameters, without parametric assumptions about the states’ sojourn distributions. The validity of the proposed methodology is analyzed both by a simulation study and through the empirical analysis of air pollutant concentrations in a small Italian city

Dolphin Morbillivirus in Eurasian Otters, Italy

We report biomolecular evidence of dolphin morbillivirus in 4 wild Eurasian otters (Lutra lutra) from southern Italy; 2 animals showed simultaneous immunohistochemical reactivity against morbilliviral antigen. These cases add further concern and support to the progressively expanding host range of dolphin morbillivirus in the western Mediterranean Sea

A New Approach in the Management of Triangular Fossa Auricular Defects: The Posterior Auricular Artery Perforator Antihelix-Conchal Flap (PAAP Flap).

Background: The reconstruction of extensive scapha or triangular fossa defects to the ear still represents a challenge considering the lack of local simple surgical procedures. Objective: To present a new perforator flap which is a modification of the Elsahy and Ladocsi chondrocutaneous rotation flaps. Patients and Methods: Ten patients, in whom the oncological resection to the triangular fossa did not include cartilage, but skin and perichondrium. Defects no larger than 3 cm in diameter were treated. The dissection of the flap was carried out from lateral to medial on the anterior subperichondral plane. The flap was thus raised without the cartilage component but with the anterior perichondrium branched with the perforating vessels. Results: All flaps survived and treated patients presented good aesthetic results. Conclusions: We think that this procedure represents a valuable option to be considered in reconstructing well selected composite defects to upper ear

Dolphin Morbillivirus Associated with a Mass Stranding of Sperm Whales, Italy

In September 2014, 7 sperm whales stranded along the Adriatic Italian coastlines. Postmortem investigations on 3 dead females dead and in 1 fetus harbored by the largest one revealed molecular and immunoistochemical evidences of dolphin morbillivirus infection. A possible role of the virus in the stranding event was considered

Molecular pathology, oxidative stress, and biomarkers in obstructive sleep apnea

Obstructive sleep apnea syndrome (OSAS) is characterized by intermittent hypoxia (IH) during sleep due to recurrent upper airway obstruction. The derived oxidative stress (OS) leads to complications that do not only concern the sleep-wake rhythm but also systemic dysfunctions. The aim of this narrative literature review is to investigate molecular alterations, diagnostic markers, and potential medical therapies for OSAS. We analyzed the literature and synthesized the evidence collected. IH increases oxygen free radicals (ROS) and reduces antioxidant capacities. OS and metabolic alterations lead OSAS patients to undergo endothelial dysfunction, osteoporosis, systemic inflammation, increased cardiovascular risk, pulmonary remodeling, and neurological alterations. We treated molecular alterations known to date as useful for understanding the pathogenetic mechanisms and for their potential application as diagnostic markers. The most promising pharmacological therapies are those based on N-acetylcysteine (NAC), Vitamin C, Leptin, Dronabinol, or Atomoxetine + Oxybutynin, but all require further experimentation. CPAP remains the approved therapy capable of reversing most of the known molecular alterations; future drugs may be useful in treating the remaining dysfunctions

Diagnostic predictors of immunotherapy response in head and neck squamous cell carcinoma

Programmed cell death ligand-1 (PD-L1) binds PD-1 on CD8+ lymphocytes, inhibiting their cytotoxic action. Its aberrant expression by head and neck squamous cell carcinoma (HNSCC) cells leads to immune escape. Pembrolizumab and nivolumab, two humanized monoclonal antibodies against PD-1, have been approved in HNSCC treatment, but similar to 60% of patients with recurrent or metastatic HNSCC fail to respond to immunotherapy and only 20 to 30% of treated patients have long-term benefits. The purpose of this review is to analyze all the fragmentary evidence present in the literature to identify what future diagnostic markers could be useful for predicting, together with PD-L1 CPS, the response to immunotherapy and its durability. We searched PubMed, Embase, and the Cochrane Register of Controlled Trials and we summarize the evidence collected in this review. We confirmed that PD-L1 CPS is a predictor of response to immunotherapy, but it should be measured across multiple biopsies and repeatedly over time. PD-L2, IFN-gamma, EGFR, VEGF, TGF-beta, TMB, blood TMB, CD73, TILs, alternative splicing, tumor microenvironment, and some macroscopic and radiological features are promising predictors worthy of further studies. Studies comparing predictors appear to give greater potency to TMB and CXCR9

Spatial genetic structure in the Eurasian otter (Lutra lutra) meta-population from its core range in Italy

We characterized the genetic structure of the Eurasian otter (Lutra lutra) meta-population living in the core of its Italian distribution range providing results from 191 fresh spraints, collected from 24 watercourses included in Southern Italy. Furthermore, according to ecological corridors and barriers, we discuss the likely ways of movement and possible evolutionary fate of these populations. We genotyped 136 samples using 11 Lut microsatellite nuclear markers amplified from faecal dna. Microsatellites were moderately variable (Ho = 0.45; He = 0.46), with a total number of alleles and average number of alleles per locus in the meta-population of 50 and 4.54, respectively. No significant heterozygosity excess was observed in meta-population suggesting no recent population bottlenecks. Bayesian clustering discriminated a sub-structuring of the meta-population in five putative clusters, indicating that local populations are genetically differentiated: three of these seem to be identifiable with geographically defined sub-populations (from the Cilento, Agri and Basento river basins). The fourth is represented by multiple sub-populations with admixed genotype, that include genotypes from the Lao, Sinni and Abatemaco river basins, living in a landscape with the higher environmental permeability. Landscape genetic analysis could provide evidence of an unexpected ecological corridor: the seacoast, highlighted, for the first time as a new way for the dispersion of the South-Italian otters. Deepening the knowledge of these perspectives is crucial to identify solid strategies aimed at the future health of the populations of the Italian otters, by restoring dispersal corridors and managing the watercourses