Beyond the Shade of the Oak Tree: The Recent Growth of Johannine Studies

The recent growth within Johannine studies has developed as a result of several factors. First, the discovery of the Dead Sea Scrolls led to an appreciation of the Jewishness of John’s origin. Second, new approaches to John’s composition have emerged, followed by a larger set of inquiries as to the Johannine tradition’s relation to parallel traditions. This has been accompanied by a fourth interest: the history of the Johannine situation. Fifth, new literary studies have posed new horizons for interpretation, and sixth, theories continue to abound on the identity of the Beloved Disciple. A seventh development involves new ways of conceiving John’s theological features, leading to an eighth: reconsidering John’s historical features and re-envisioning its historical contributions in new perspective

The management of diabetic ketoacidosis in children

The object of this review is to provide the definitions, frequency, risk factors, pathophysiology, diagnostic considerations, and management recommendations for diabetic ketoacidosis (DKA) in children and adolescents, and to convey current knowledge of the causes of permanent disability or mortality from complications of DKA or its management, particularly the most common complication, cerebral edema (CE). DKA frequency at the time of diagnosis of pediatric diabetes is 10%–70%, varying with the availability of healthcare and the incidence of type 1 diabetes (T1D) in the community. Recurrent DKA rates are also dependent on medical services and socioeconomic circumstances. Management should be in centers with experience and where vital signs, neurologic status, and biochemistry can be monitored with sufficient frequency to prevent complications or, in the case of CE, to intervene rapidly with mannitol or hypertonic saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours; an initial bolus of 10–20 mL/kg 0.9% saline is followed by 0.45% saline calculated to supply maintenance and replace 5%–10% dehydration. Potassium (K) must be replaced early and sufficiently. Bicarbonate administration is contraindicated. The prevention of DKA at onset of diabetes requires an informed community and high index of suspicion; prevention of recurrent DKA, which is almost always due to insulin omission, necessitates a committed team effort

Realization and testing of an active mirror mechanism for in-field pointing in eLISA

An active tilt mirror mechanism, meant for correction of the constellation breathing of the evolved Laser Interferometer Space Antenna, has been designed and realized. Its open-loop performance has been characterized in both time and frequency domain. Based on this, a feedback controller has been designed and the resulting closed-loop performance has been assessed. Up to what is measurable in a normal lab environment, these experiments demonstrate compliance with the extreme pointing jitter requirement, even when using the internal encoder as feedback sensor

Nanometer level freeform surface measurements with the NANOMEFOS non-contact measurement machine

TNO, TU/e and NMi VSL have developed the NANOMEFOS measurement machine, This machine is capable of fast, universal and non-contact measurement of freeform optics up to 500 mm diameter, with an uncertainty of 30 nm. The optic is placed on a continuously rotating spindle, while a specially developed long range optical probe is positioned over it by a motion system. A separate metrology system measures probe and product position. Measurements of a tilted flat show a reproducibility of 2-4 nm rms. More complex artifacts are measured, and further calibrations are shown to demonstrate the nanometer level measurement uncertainty

Evaluation of pharmacogenomics and hepatic nuclear imaging–related covariates by population pharmacokinetic models of irinotecan and its metabolites

Published online: 4 September 2021Background Body surface area (BSA)–based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. Methods Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants. Results Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%. Conclusion The identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.Zheng Liu ... Timothy Price ... et al