In the Hellenistic-Roman world, both philosophical schools (Platonists) and ethnic groups (Romans, Athenians, Judeans) were committed to the authority of founder figures. Dionysius, Josephus, and ...Luke included biographies of their founders (Romulus, Moses, Jesus) within their historical works. Luke-Acts also acculturated Roman politics: 1) Luke narrated the official leadership of early Pauline assemblies exclusively by males, not narrating earlier leadership by women (Junia, Euodia, Syntyche). 2) Luke gave Jesus an inaugural address “to declare God’s age open and welcome to all nations” (Luke 4:19 quoting Isa 61:2), urging Luke’s auditors to become multiethnic. Peter instituted this crossing of ethnic boundaries in Judea (Acts 10) and Paul “accepted all” in Rome (Acts 28:30), the concluding sentence of the two volumes.
In the Hellenistic-Roman world, both philosophical schools (Platonists) and ethnic groups (Romans, Athenians, Judeans) were committed to the authority of founder figures. Dionysius, Josephus, and ...Luke included biographies of their founders (Romulus, Moses, Jesus) within their historical works. Luke-Acts also acculturated Roman politics: 1) Luke narrated the official leadership of early Pauline assemblies exclusively by males, not narrating earlier leadership by women (Junia, Euodia, Syntyche). 2) Luke gave Jesus an inaugural address “to declare God’s age open and welcome to all nations” (Luke 4:19 quoting Isa 61:2), urging Luke’s auditors to become multiethnic. Peter instituted this crossing of ethnic boundaries in Judea (Acts 10) and Paul “accepted all” in Rome (Acts 28:30), the concluding sentence of the two volumes.
Background
For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these ...factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS.
Patients and Methods
NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24–72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.
Results
A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.
Conclusions
Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
The article has three parts. First, I sketch debates concerning the origins, function, and history of religions context of the Lukan birth narrative and its canticles. Second, I outline the ...urban–rural conflict between patricians/aristocrats and plebleians in Rome as narrated by Dionysius of Halicarnassus. Dionysius's Greek terminology is identical to the vocabulary of Mary's Magnificat in Luke 1, including the contrasts between the proud rich and the hungry humble. I then glance at Carol Wilson's recent model of how poor persons scratched out a living in the Roman Empire and how changes in their circumstances would drive them below subsistence level. Dionysius's narrative and Wilson's model correspond to an amazing degree. Given this economic interpretation of the Magnificat, I record how contemporary corporations' investments in Mexico deprive farmers of their land and living, generating migration through poverty, a significant parallel to Dionysius's narrative, Wilson's model, and the Magnificat.
The article has three parts. First, I sketch debates concerning the origins, function, and history of religions context of the Lukan birth narrative and its canticles. Second, I outline the ...urban–rural conflict between patricians/aristocrats and plebleians in Rome as narrated by Dionysius of Halicarnassus. Dionysius's Greek terminology is identical to the vocabulary of Mary's Magnificat in Luke 1, including the contrasts between the proud rich and the hungry humble. I then glance at Carol Wilson's recent model of how poor persons scratched out a living in the Roman Empire and how changes in their circumstances would drive them below subsistence level. Dionysius's narrative and Wilson's model correspond to an amazing degree. Given this economic interpretation of the Magnificat, I record how contemporary corporations' investments in Mexico deprive farmers of their land and living, generating migration through poverty, a significant parallel to Dionysius's narrative, Wilson's model, and the Magnificat.
We aimed to evaluate the performance of Oxford Nanopore Technologies (ONT) sequencing from positive blood culture (BC) broths for bacterial identification and antimicrobial susceptibility prediction. ...Patients with suspected sepsis in four intensive care units were prospectively enrolled. Human-depleted DNA was extracted from positive BC broths and sequenced using ONT (MinION). Species abundance was estimated using Kraken2, and a cloud-based system (AREScloud) provided
predictive antimicrobial susceptibility testing (AST) from assembled contigs. Results were compared to conventional identification and phenotypic AST. Species-level agreement between conventional methods and AST predicted from sequencing was 94.2% (49/52), increasing to 100% in monomicrobial infections. In 262 high-quality AREScloud AST predictions across 24 samples, categorical agreement (CA) was 89.3%, with major error (ME) and very major error (VME) rates of 10.5% and 12.1%, respectively. Over 90% CA was achieved for some taxa (e.g.,
) but was suboptimal for
. In 470 AST predictions across 42 samples, with both high quality and exploratory-only predictions, overall CA, ME, and VME rates were 87.7%, 8.3%, and 28.4%. VME rates were inflated by false susceptibility calls in a small number of species/antibiotic combinations with few representative resistant isolates. Time to reporting from sequencing could be achieved within 8-16 h from BC positivity. Direct sequencing from positive BC broths is feasible and can provide accurate predictive AST for some species. ONT-based approaches may be faster but significant improvements in accuracy are required before it can be considered for clinical use.IMPORTANCESepsis and bloodstream infections carry a high risk of morbidity and mortality. Rapid identification and susceptibility prediction of causative pathogens, using Nanopore sequencing direct from blood cultures, may offer clinical benefit. We assessed this approach in comparison to conventional phenotypic methods and determined the accuracy of species identification and susceptibility prediction from genomic data. While this workflow holds promise, and performed well for some common bacterial species, improvements in sequencing accuracy and more robust predictive algorithms across a diverse range of organisms are required before this can be considered for clinical use. However, results could be achieved in timeframes that are faster than conventional phenotypic methods.
Purpose
Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) ...setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU.
Methods
A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre–post-design).
Results
175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively,
p
= 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (
n
= 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively,
p
< 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01–0.05,
p
< 0.01). There was no difference observed in in-hospital mortality.
Conclusions
Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.
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