One of the most widely debated topics in Slavic linguistics has always been verbal aspect, which takes different forms because of the various grammaticalization paths which led to its emergence. In ...the formation of the category of aspect in Slavic languages, a key role was played by the morphological mechanism of prefixation (a.k.a. preverbation), whereby the prefixes (which originally performed the function of markers of adverbial meanings) came to act as markers of boundedness. This volume contains thirteen articles on the mechanism of prefixation, written by leading international scholars in the field of verbal aspect. Ancient and modern Slavic varieties, as well as non-Slavic and even non-Indo-European languages, are represented, making the volume an original and significant contribution to Slavic as well as typological linguistics.
Under N(oun)I(ncorporation), a N stem is compounded with a V stem to yield a complex V stem. After a survey of the most important approaches to the phenomenon, this paper describes some distinctions ...which have received little attention in the literature, mainly regarding the directionality and adjacency of the components. A new approach is introduced which distinguishes between incorporated XP Ns (preverbal) and X° Ns (postverbal): this approach is shown to clearly capture the alternations. KEYWORDS: noun incorporation, polysynthesis, morphology-syntax interface, native American languages, paleosiberian languages
The term preverb stacking (PS) designates the co-occurrence on one verbal base of two or more prefixes bearing spatial, aspectual, or quantificational meanings. The phenomenon is especially ...productive in Slavic but is also attested in other Indo-European and non-Indo-European languages. This paper provides a first attempt at a cross-linguistic typology of PS. It will also pay attention to problems typical of Slavic (i.e. the interaction of PS and the aspectual value of the verb in terms of the typical Slavic perfective vs. imperfective dichotomy). Special attention will be paid to Bulgarian.
IMPORTANCE: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. OBJECTIVE: To assess whether helmet ...noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). INTERVENTIONS: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). MAIN OUTCOMES AND MEASURES: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. RESULTS: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years interquartile range {IQR}, 55-70; 21 women 19%). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days 95% CI, −2 to 6; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, −21% 95% CI, −38% to −3%; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 IQR, 13-28 vs 25 IQR 4-28; mean difference, 3 days 95% CI, 0-7; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, −1% 95% CI, −17% to 15%; P > .99). CONCLUSIONS AND RELEVANCE: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04502576
The liver is an essential organ of the body that performs several vital functions, including the metabolism of biomolecules, foreign substances, and toxins, and the production of plasma proteins, ...such as coagulation factors. There are hundreds of genetic disorders affecting liver functions and, for many of them, the only curative option is orthotopic liver transplantation, which nevertheless entails many risks and long-term complications. Some peculiar features of the liver, such as its large blood flow supply and the tolerogenic immune environment, make it an attractive target for in vivo gene therapy approaches. In recent years, several genome-editing tools mainly based on the clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) system have been successfully exploited in the context of liver-directed preclinical or clinical therapeutic applications. These include gene knock-out, knock-in, activation, interference, or base and prime editing approaches. Despite many achievements, important challenges still need to be addressed to broaden clinical applications, such as the optimization of the delivery methods, the improvement of the editing efficiency, and the risk of on-target or off-target unwanted effects and chromosomal rearrangements. In this review, we highlight the latest progress in the development of in vivo liver-targeted genome editing approaches for the treatment of genetic disorders. We describe the technological advancements that are currently under investigation, the challenges to overcome for clinical applicability, and the future perspectives of this technology.The liver is an essential organ of the body that performs several vital functions, including the metabolism of biomolecules, foreign substances, and toxins, and the production of plasma proteins, such as coagulation factors. There are hundreds of genetic disorders affecting liver functions and, for many of them, the only curative option is orthotopic liver transplantation, which nevertheless entails many risks and long-term complications. Some peculiar features of the liver, such as its large blood flow supply and the tolerogenic immune environment, make it an attractive target for in vivo gene therapy approaches. In recent years, several genome-editing tools mainly based on the clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) system have been successfully exploited in the context of liver-directed preclinical or clinical therapeutic applications. These include gene knock-out, knock-in, activation, interference, or base and prime editing approaches. Despite many achievements, important challenges still need to be addressed to broaden clinical applications, such as the optimization of the delivery methods, the improvement of the editing efficiency, and the risk of on-target or off-target unwanted effects and chromosomal rearrangements. In this review, we highlight the latest progress in the development of in vivo liver-targeted genome editing approaches for the treatment of genetic disorders. We describe the technological advancements that are currently under investigation, the challenges to overcome for clinical applicability, and the future perspectives of this technology.
We produced a new suite of sea-level data which allowed assessing the Holocene evolution of the Bonifacio Strait, a key coastal sector of the Mediterranean Sea which experienced significant ...morphological changes since the Last Glacial Maximum. Squeezed between Corsica and Sardinia islands, this strait connects the two major basins of the western Mediterranean. Due to its peculiar geographic and morphological setting, the Bonifacio Strait is affected by extreme meteomarine conditions characterized by severe winds, waves, and currents.
The millennial sea-level changes were reconstructed through multiproxy investigations made of sediment coring and underwater beachrock sampling carried out on both sides of the strait. These data provided fresh insights into the timing of the progressive opening of the Bonifacio Strait which followed the Last Glacial Maximum when Corsica and Sardinia were connected forming the largest Mediterranean island. Major palaeogeographic changes occurred before ~7 ka BP. Since that period, the significant decrease of the northern ice-sheet melting triggered a significant sea-level stabilization which induced only minor modifications in the palaeogeography of the strait. In the late Holocene, the isostatic-related subsidence became the dominant factor controlling the sea-level changes which rose with rates ≤0.35 mm a−1 in the last four millennia.
Our data have also an important archaeological implication because they indicate that the Bonifacio Strait has not represented a significant geographical barrier along the early Neolithic migration path which connected mainland Italy to northern Corsica and finally to Sardinia. This further confirms the ability of early Neolithic communities to navigate not also across large sea stretches but also maritime areas characterized by extremely complex meteomarine conditions.
•An analysis of the postglacial evolution the Bonifacio strait•The Bonifacio strait is a key coastal area of western Mediterranean•New insights into the timing of progressive opening of the strait were provided•Major paleogeographic changes occurred before ~7 ka BP•Sea-level rose with rates ≤0.35 mm a−1 in the last four millennia•The strait did not represent a geographical barrier for early Neolithic migrations
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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