40 research outputs found

    Criteri di buona governance in Leader: l\u2019autovalutazione dei Gruppi di Azione Locale

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    l principale obiettivo di questo lavoro \ue8 proporre una metodologia per l\u2019autovalutazione della capacit\ue0 del Gruppi di Azione Locale (Gal) di elaborare e gestire una strategia locale Leader secondo principi di buona governance. L\u2019approccio proposto, inizialmente sviluppato e testato in via preliminare con tecniche di ricerca qualitativa \ue8 qui perfezionato e integrato con il Common Assessment Framework (Caf), un modello di autovalutazione in uso da tempo presso organizzazioni pubbliche in Europa. Il sistema proposto si basa su un set d\u2019indicatori specifici di prestazione (performance) e di percezione del Gal capaci di correlare i principali elementi di una buona governance alle specificit\ue0 dell\u2019approccio Leader. Questo strumento pu\uf2 contribuire a migliorare l\u2019attivit\ue0 di monitoraggio gestionale e indirizzare criticamente le attivit\ue0 del Gal

    Levetiracetam versus Phenobarbital for Neonatal Seizures: A Retrospective Cohort Study

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    BACKGROUND Although phenobarbital (PB) is commonly used as a first-line antiseizure medication (ASM) for neonatal seizures, in 2015 we chose to replace it with levetiracetam (LEV), a third-generation ASM. Here, we compared the safety and efficacy of LEV and PB as first-line ASM, considering the years before and after modifying our treatment protocol. METHODS We conducted a retrospective cohort study of 108 neonates with electroencephalography (EEG)-confirmed seizures treated with first-line LEV or PB in 2012 to 2020. RESULTS First-line ASM was LEV in 33 (31%) and PB in 75 (69%) neonates. The etiology included acute symptomatic seizures in 69% of cases (30% hypoxic-ischemic encephalopathy, 32% structural vascular, 6% infectious, otherwise metabolic) and neonatal epilepsy in 22% (5% structural due to brain malformation, 17% genetic). Forty-two of 108 (39%) neonates reached seizure freedom following first-line therapy. Treatment response did not vary by first-line ASM among all neonates, those with acute symptomatic seizures, or those with neonatal-onset epilepsy. Treatment response was lowest for neonates with a higher seizure frequency, particularly for those with status epilepticus versus rare seizures (P < 0.001), irrespective of gestational age, etiology, or EEG findings. Adverse events were noted in 22 neonates treated with PB and in only one treated with LEV (P < 0.001). CONCLUSIONS Our study suggests a potential noninferiority and a more acceptable safety profile for LEV, which may thus be a reasonable option as first-line ASM for neonatal seizures in place of PB. Treatment should be initiated as early as possible since higher seizure frequencies predispose to less favorable responses

    A trimeric DNA polymerase complex increases the native replication processivity

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    DNA polymerases are essential enzymes in all domains of life for both DNA replication and repair. The primary DNA replication polymerase from Sulfolobus solfataricus (SsoDpo1) has been shown previously to provide the necessary polymerization speed and exonuclease activity to replicate the genome accurately. We find that this polymerase is able to physically associate with itself to form a trimer and that this complex is stabilized in the presence of DNA. Analytical gel filtration and electrophoretic mobility shift assays establish that initially a single DNA polymerase binds to DNA followed by the cooperative binding of two additional molecules of the polymerase at higher concentrations of the enzyme. Protein chemical crosslinking experiments show that these are specific polymerase–polymerase interactions and not just separate binding events along DNA. Isothermal titration calorimetry and fluorescence anisotropy experiments corroborate these findings and show a stoichiometry where three polymerases are bound to a single DNA substrate. The trimeric polymerase complex significantly increases both the DNA synthesis rate and the processivity of SsoDpo1. Taken together, these results suggest the presence of a trimeric DNA polymerase complex that is able to synthesize long DNA strands more efficiently than the monomeric form

    The Importance of Getting Names Right: The Myth of Markets for Water

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