Hemodynamic support in the early phase of septic shock: a review of challenges and unanswered questions

BACKGROUND: Improving sepsis support is one of the three pillars of a 2017 resolution according to the World Health Organization (WHO). Septic shock is indeed a burden issue in the intensive care units. Hemodynamic stabilization is a cornerstone element in the bundle of supportive treatments recommended in the Surviving Sepsis Campaign (SSC) consecutive biannual reports. MAIN BODY: The "Pandera\u27s box" of septic shock hemodynamics is an eternal debate, however, with permanent contentious issues. Fluid resuscitation is a prerequisite intervention for sepsis rescue, but selection, modalities, dosage as well as duration are subject to discussion while too much fluid is associated with worsen outcome, vasopressors often need to be early introduced in addition, and catecholamines have long been recommended first in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has come out. Preservation of the macrocirculation through a "best" mean arterial pressure target is the actual priority but is still contentious. Microcirculation recruitment is a novel goal to be achieved but is claiming more knowledge and monitoring standardization. Protection of the cardio-renal axis, which is prevalently injured during septic shock, is also an unavoidable objective. Several promising alternative or additive drug supporting avenues are emerging, trending toward catecholamine\u27s sparing or even "decatecholaminization." Topics to be specifically addressed in this review are: (1) mean arterial pressure targeting, (2) fluid resuscitation, and (3) hemodynamic drug support. CONCLUSION: Improving assessment and means for rescuing hemodynamics in early septic shock is still a work in progress. Indeed, the bigger the unresolved questions, the lower the quality of evidence

Exploration of the maritime façade of Utica: The potential location of the Phoenician and Roman harbours

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Exploration of the maritime façade of Utica: the potential location of the Phoenician and Roman harbours

According to ancient literary tradition, Utica is considered to be one of the first three Phoenician foundations in the Western Mediterranean, supposedly founded in 1101 BC by Levantines from Tyre. In the Phoenician and Roman periods, it was an important merchant coastal town, on a promontory facing the sea. Over the centuries Utica lost its access to the sea, and its ports silted up as a consequence of the activity of the wadi Medjerda, which flowed to the south of the city. Despite over a century of investigation by archaeologists and associated researchers, the location of the city's harbour structures from the Phoenician and Roman periods remains unknown, buried under sediments resulting from the progradation of the Medjerda. Based on the study of sedimentary cores, the research presented here highlights the existence of a long maritime façade to the north of the Utica promontory in Phoenician and Roman times. A deep-water marine environment is attested in the former bay from the 6th mill. BC and the depth of the water column along the northern façade was still 2 m around the 4th – 3rd c. BC. Another core to the east of the Kalaat El Andalous promontory showed the possibility that this sector was a sheltered harbour during the Phoenician and Roman periods. This paper illustrates the contribution of geoarchaeology to address this archaeological problem and to understand the relations of this important port city with the sea

Exploration of the maritime façade of Utica: the potential location of the Phoenician and Roman harbours

peer reviewedAccording to ancient literary tradition, Utica is considered to be one of the first three Phoenician foundations in the Western Mediterranean, supposedly founded in 1101 BC by Levantines from Tyre. In the Phoenician and Roman periods, it was an important merchant coastal town, on a promontory facing the sea. Over the centuries Utica lost its access to the sea, and its ports silted up as a consequence of the activity of the wadi Medjerda, which flowed to the south of the city. Despite over a century of investigation by archaeologists and associated researchers, the location of the city’s harbour structures from the Phoenician and Roman periods remains unknown, buried under sediments resulting from the progradation of the Medjerda. Based on the study of sedimentary cores, the research presented here highlights the existence of a long maritime façade to the north of the Utica promontory in Phoenician and Roman times. A deep-water marine environment is attested in the former bay from the 6th mill. BC and the depth of the water column along the northern façade was still 2 m around the 4th – 3rd c. BC. Another core to the east of the Kalaat El Andalous promontory showed the possibilitythat this sector was a sheltered harbour during the Phoenician and Roman periods. This paper illustrates the contribution of geoarchaeology to address this archaeological problem and to understand the relations of this important port city with the sea

Changes in biochemical and sensory parameters in industrial blue-veined cheeses in different packaging

International audienceThe effects of packaging on the biochemical and sensory characteristics of industrial blue-veined cheese (pieces of cheeses pre-packaged in materials of different permeability and whole cheeses traditionally wrapped in aluminium foil) were evaluated over 43 days of storage. In cheese pieces in reduced-O-2 packaging, less ammonia production and lower proteolysis were observed. Packaged cheese pieces were distinguished from controls by higher levels of (a) methyl ketones and their corresponding alcohols and acids, (b) methyl acids derived from branched chain amino acids and (c) esters. This may be due to less oxidation. Packaged cheese pieces were also more acid, with more pungency, creaminess and milky odour and less bitterness than the control cheeses. They have high moisture content, owing to the low water vapour permeability of the films. Fourme d'Ambert cheese pieces wrapped in permeable film behaved similarly to the corresponding control throughout storage

The economic resilience of Carthage during the Punic Wars: Insights from the sediments of the Medjerda delta around Utica (Tunisia)

While the Punic Wars (264–146 BC) have been the subject of numerous studies, generally focused on their most sensational aspects (major battles, techniques of warfare, geopolitical strategies, etc.), curiously, the exceptional economic resilience of the Carthaginians in the face of successive defeats, loss of mining territory, and the imposition of war reparations has attracted hardly any attention. Here, we address this issue using a newly developed powerful tracer in geoarchaeology, that of Pb isotopes applied to paleopollution. We measured the Pb isotopic compositions of a well-dated suite of eight deep cores taken in the Medjerda delta around the city of Utica. The data provide robust evidence of ancient lead–silver mining in Tunisia and lay out a chronology for its exploitation, which appears to follow the main periods of geopolitical instability at the time: the Greco-Punic Wars (480–307 BC) and the Punic Wars (264–146 BC). During the last conflict, the data further suggest that Carthage was still able to pay indemnities and fund armies despite the loss of its traditional silver sources in the Mediterranean. This work shows that the mining of Tunisian metalliferous ores between the second half of the fourth and the beginning of the third century BC contributed to the emergence of Punic coinage and the development of the Carthaginian economy

Palaeogeographical and palaeoenvironmental reconstruction of the Medjerda delta (Tunisia) during the Holocene

International audienceThe progradation of the Medjerda delta has been the subject of many studies since the 19th century. Thescale and the rapidity of this phenomenon interested researchers in various fields early on, such asgeomorphology, geology, palaeogeography, history, archaeology, or geoarchaeology. Indeed, the deltaprograded by around 10 km over 3 millennia. At the time of its foundation supposedly at the end of the12th century BC, the Phoenician city of Utica was located on a promontory bathed by the sea, but thesediments carried by the Medjerda progressively sealed the bay, leaving the tip of the Utica promontorynow 10 km inland. This area is therefore an exception to the general pattern along the Tunisian coast,since as over the same period everywhere else there is a regression of the coastline, owing to a sea levelrise of several decimeters. Based on multi-proxy analyses of two coring transects, this paper aims toreconstruct the palaeoenvironments and the palaeogeography of the Medjerda delta’s progradation sincethe mid-Holocene, some aspects of which are described in ancient sources. The results highlight inparticular an episode of high-intensity flooding around the 4th century AD, which is consistent withepisodes of high floods and an increase in sedimentation rates recorded in the watershed at the end ofthe Roman period. The gradual abandonment of the city of Utica can certainly be related to the activity ofthe Medjerda River, but our results show that it is because of an increase of fluvial sediment contributionin connection with an erosive crisis in the headwaters, and not because of the change of course of theriver, which had occurred long before

Economic resilience of Carthage during the Punic Wars: Insights from sediments of the Medjerda delta around Utica (Tunisia).

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Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics

<div><p>During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.</p></div