Recent updates in mechanical ventilation

Recently, several studies have been performed to better outline the pathophysiology of acute respiratory failure and evaluate the therapeutic profile of different modes of ventilation and ventilator settings. Here we briefly report those we consider most relevant for daily intensive care unit clinical practice

BFGS-like updates of constraint preconditioners for sequences of KKT linear systems in quadratic programming

We focus on efficient preconditioning techniques for sequences of KKT linear systems arising from the interior point solution of large convex quadratic programming problems. Constraint Preconditioners~(CPs), though very effective in accelerating Krylov methods in the solution of KKT systems, have a very high computational cost in some instances, because their factorization may be the most time-consuming task at each interior point iteration. We overcome this problem by computing the CP from scratch only at selected interior point iterations and by updating the last computed CP at the remaining iterations, via suitable low-rank modifications based on a BFGS-like formula. This work extends the limited-memory preconditioners for symmetric positive definite matrices proposed by Gratton, Sartenaer and Tshimanga in [SIAM J. Optim. 2011; 21(3):912--935, by exploiting specific features of KKT systems and CPs. We prove that the updated preconditioners still belong to the class of exact CPs, thus allowing the use of the conjugate gradient method. Furthermore, they have the property of increasing the number of unit eigenvalues of the preconditioned matrix as compared to generally used CPs. Numerical experiments are reported, which show the effectiveness of our updating technique when the cost for the factorization of the CP is high

A Catalytic and Selective Scissoring Molecular Tool for Quadruplex Nucleic Acids

A copper complex embedded in the structure of a water-soluble naphthalene diimide has been designed to bind and cleave G-quadruplex DNA. We describe the properties of this ligand, including its catalytic activity in the generation of ROS. FRET melting, CD, NMR, gel sequencing, and mass spectrometry experiments highlight a unique and unexpected selectivity in cleaving G-quadruplex sequences. This selectivity relies both on the binding affinity and structural features of the targeted G-quadruplexes

Gli uccelli della provincia di Novara (Piemonte, Italia): distribuzione, abbondanza e stato di conservazione

In questo lavoro viene riportato un elenco commentato degli uccelli noti per la provincia di Novara (1.340 km2) aggiornato al 31/12/2016 e vengono forniti dati di sintesi relativi alle attività di monitoraggio condotte in anni recenti (2009-2016). I dati sono stati raccolti sia attraverso revisione bibliografica sia attraverso attività di ricerca diretta sul campo. L'avifauna della provincia di Novara annovera o ha annoverato (dal 1860 al 2016) 304 specie delle quali 135 nidificanti certe o probabili in tempi recenti (dopo il 2000), 85 di interesse comunitario (Allegato I della Direttiva "Uccelli"), 116 SPEC - Species of European Conservation Concern secondo BirdLife International e 53 inserite nella European Red List of Birds. L'area è di importanza europea e/o nazionale per la nidificazione di specie di interesse conservazionistico quali Egretta garzetta (650-1.100 nidi), Nycticorax nycticorax (200-300 nidi), Botaurus stellaris (5-7 maschi cantori), Ciconia nigra (1-2 coppie), Ciconia ciconia (4-6 coppie), Himantopus himantopus (300-500 coppie), Vanellus vanellus (500-600 coppie), Columba oenas (20-30 coppie), nonché per la migrazione di Philomachus pugnax (5.000-7.000 ind.) e Tringa glareola (500-1.500 ind.). Negli ultimi anni (2009-2016) si segnalano in particolare: la nidificazione accertata per la prima volta nel Novarese di Ardea alba, Galerida cristata e Lullula arborea; il ritorno di Burhinus oedicnemus e Chlidonias niger in periodo riproduttivo dopo decenni di assenza; la colonizzazione da parte di Dryocopus martius degli ambienti forestali di collina e di pianura.</p

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome

Objective Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values. Design Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study. Methods Participants (n\u2009=\u2009102) aged 38.9 \ub1 7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT). Results There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI and cIMT remained directly correlated but to a lesser degree. Conclusions This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS

Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation

BACKGROUND: Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. OBJECTIVES: We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 microm (PM(10)). METHODS: We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM(10) exposure was between 73.4 and 1,220 microg/m(3). RESULTS: Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM(10) exposure levels were negatively associated with methylation in both Alu [beta = -0.19 \%5-methylcytosine (\%5mC); p = 0.04] and LINE-1 [beta = -0.34 \%5mC; p = 0.04], likely reflecting long-term PM(10) effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = -0.61 \%5mC; p = 0.02). CONCLUSIONS: We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM

The On-Site Analysis of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) observatory will be one of the largest ground-based very high-energy gamma-ray observatories. The On-Site Analysis will be the first CTA scientific analysis of data acquired from the array of telescopes, in both northern and southern sites. The On-Site Analysis will have two pipelines: the Level-A pipeline (also known as Real-Time Analysis, RTA) and the level-B one. The RTA performs data quality monitoring and must be able to issue automated alerts on variable and transient astrophysical sources within 30 seconds from the last acquired Cherenkov event that contributes to the alert, with a sensitivity not worse than the one achieved by the final pipeline by more than a factor of 3. The Level-B Analysis has a better sensitivity (not be worse than the final one by a factor of 2) and the results should be available within 10 hours from the acquisition of the data: for this reason this analysis could be performed at the end of an observation or next morning. The latency (in particular for the RTA) and the sensitivity requirements are challenging because of the large data rate, a few GByte/s. The remote connection to the CTA candidate site with a rather limited network bandwidth makes the issue of the exported data size extremely critical and prevents any kind of processing in real-time of the data outside the site of the telescopes. For these reasons the analysis will be performed on-site with infrastructures co-located with the telescopes, with limited electrical power availability and with a reduced possibility of human intervention. This means, for example, that the on-site hardware infrastructure should have low-power consumption. A substantial effort towards the optimization of high-throughput computing service is envisioned to provide hardware and software solutions with high-throughput, low-power consumption at a low-cost.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape