20 research outputs found
Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.
Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3âmonths of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (nâ=â401) from 167 patients and opportunistic CSF samples (nâ=â78) from 56 patients were analysed. Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70âkg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6âg/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered
Patterns of non-compliant buprenorphine, levomethadone, and methadone use among opioid dependent persons in treatment
Observation of gravitational waves from the coalescence of a 2.5â4.5 Mâ compact object and a neutron star
Questioning hagfish affinities of the enigmatic Devonian vertebrate Palaeospondylus
Palaeospondylus gunni Traquair, 1890 is an enigmatic Devonian vertebrate whose taxonomic affinities have been debated since it was first described. Most recently, Palaeospondylus has been identified as a stem-group hagfish (Myxinoidea). However, one character questioning this assignment is the presence of three semicircular canals in the otic region of the cartilaginous skull, a feature of jawed vertebrates. Additionally, new tomographic data reveal that the following characters of crown-group gnathostomes (chondrichthyans+osteichthyans) are present in Palaeospondylus: a longer telencephalic region of the braincase, separation of otic and occipital regions by the otico-occipital fissure, and vertebral centra. As well, a precerebral fontanelle and postorbital articulation of the palatoquadrate are characteristic of certain chondrichthyans. Similarities in the structure of the postorbital process to taxa such as Pucapampella, and possible presence of the ventral cranial fissure, both support a resolution of Pa. gunni as a stem chondrichthyan. The internally mineralized cartilaginous skeleton in Palaeospondylus may represent a stage in the loss of bone characteristic of the Chondrichthyes
Questioning hagfish affinities of the enigmatic Devonian vertebrate Palaeospondylus
Palaeospondylus gunni Traquair, 1890 is an enigmatic Devonian vertebrate whose taxonomic affinities have been debated since it was first described. Most recently, Palaeospondylus has been identified as a stem-group hagfish (Myxinoidea). However, one character questioning this assignment is the presence of three semicircular canals in the otic region of the cartilaginous skull, a feature of jawed vertebrates. Additionally, new tomographic data reveal that the following characters of crown-group gnathostomes (chondrichthyansâ+âosteichthyans) are present in Palaeospondylus: a longer telencephalic region of the braincase, separation of otic and occipital regions by the otico-occipital fissure, and vertebral centra. As well, a precerebral fontanelle and postorbital articulation of the palatoquadrate are characteristic of certain chondrichthyans. Similarities in the structure of the postorbital process to taxa such as Pucapampella, and possible presence of the ventral cranial fissure, both support a resolution of Pa. gunni as a stem chondrichthyan. The internally mineralized cartilaginous skeleton in Palaeospondylus may represent a stage in the loss of bone characteristic of the Chondrichthyes
ESM Figure S3 Palaeospondylus gunni, Achanarras Quarry (Devonian), Scotland. from Questioning hagfish affinities of the enigmatic Devonian vertebrate <i>Palaeospondylus</i>
Line drawing, ventral view of chondrocranium. Abbreviations: As in Figures 1, 2, S1, S2
Electronic Supplementary material - text from Questioning hagfish affinities of the enigmatic Devonian vertebrate <i>Palaeospondylus</i>
Additional text describing Palaeospondylus gunn
ESM Figure S2 Palaeospondylus gunni, Achanarras Quarry (Devonian), Scotland. from Questioning hagfish affinities of the enigmatic Devonian vertebrate <i>Palaeospondylus</i>
A, B, NHMUK PVP22393, macrophotograph of anterior axial skeleton in lateral view. B, closeup showing articulation of neural arch bases to the centra (asterisk). C, D. NHMUK PVP61428, macrophotographs showing postcranial skeleton in dorsoventral (C) and dorsal and ventral (D) views. In D, X marks position where vertebral column rotates postmortem from dorsal to ventral view. Asterisks indicate incompletely mineralized centra (unmineralised ventrally). Abbreviations: As in Figures 1, 2, also cent, centrum, haem, haemal arch