Re–Os geochronology of a Mesoproterozoic sedimentary succession, Taoudeni basin, Mauritania: Implications for basin-wide correlations and Re–Os organic-rich sediments systematics

The exceptionally well-preserved sedimentary rocks of the Taoudeni basin, NW Africa represent one of the world's most widespread (> 1 M km2) Proterozoic successions. Hitherto, the sedimentary rocks were considered to be Mid Tonian based on Rb–Sr illite and glauconite geochronology of the Atar Group. However, new Re–Os organic-rich sediment (ORS) geochronology from two drill cores indicates that the Proterozoic Atar Group is 200 Ma older (1107 ± 12 Ma, 1109 ± 22 Ma and 1105 ± 37 Ma). The Re–Os geochronology suggests that the Rb–Sr geochronology records the age of diagenetic events possibly associated with the Pan African collision. The new Re–Os geochronology data provide absolute age constraints for recent carbon isotope chemostratigraphy which suggests that the Atar Group is Mesoproterozoic and not Neoproterozoic. The new Re–Os ORS geochronology supports previous studies that suggest that rapid hydrocarbon generation (flash pyrolysis) from contact metamorphism of a dolerite sill does not significantly disturb the Re–Os ORS systematics. Modelled contact conditions suggest that the Re–Os ORS systematics remain undisturbed at 650 °C at the sill/shale contact and ≥ 280 °C 20 m from the sill/shale contact. Moreover, the Re–Os geochronology indicates that the West African craton has a depositional history that predates 1100 Ma and that ORS can be correlated on a basin-wide scale. In addition, the Re–Os depositional ages for the ORS of the Taoudeni basin are comparable to those of ORS from the São Francisco craton, suggesting that these cratons are correlatable. This postulate is further supported by identical Osi values for the Atar Group and the Vazante Group of the São Francisco craton

Clinical Characteristics of Central European and North American Samples of Pregnant Women Screened for Opioid Agonist Treatment

BACKGROUND: Little comparable information is available regarding clinical characteristics of opioid-dependent women from different countries. In the present study, women from the USA, Canada and a Central European country, Austria, screened for participation in the Maternal Opioid Treatment Human Experimental Research study, were compared with respect to their demographic and addiction histories. METHODS: Pregnant women (n = 1,074) were screened for study participation using uniformed clinical criteria and instruments. The screening results were compared with regard to exclusion, demographics, drug use, and psychosocial and treatment histories. RESULTS: Compared to the screened US and Canadian women, Austrian women were more likely to be younger (p < 0.001), white (p < 0.001), had significantly lower levels of educational attainment (p < 0.001), were less likely to use opioids daily (p < 0.001) and more likely to have been prescribed buprenorphine (p < 0.001). Compared to both rural and urban US groups, the Austrian group was less likely to have legal issues (p < 0.001) and was younger when first prescribed agonist medication (p < 0.001). CONCLUSION: The differences between North American and European groups may offer unique insights concerning treatment and pregnancy outcomes for opioid-dependent pregnant women

Optimising antifungal prophylaxis in allogeneic stem cell transplantation - a cohort study of two different approaches

Published online December 2022Background: Limited consensus exists on the optimal use of antifungal agents to prevent invasive fungal infection in the early post allogeneic hematopoietic stem cell transplant (alloHCT) period, particularly when patients cannot tolerate oral medication administration. Methods: We undertook a retrospective observational cohort study to assess the tolerability, efficacy, and cost of a new antifungal prophylaxis pathway at a major tertiary alloHCT centre. Patients aged ≥16 years who underwent alloHCT between February 2018 and October 2019 (cohort 1) or between April 2020 and November 2021 (cohort 2) were included. In both cohorts, first line prophylactic therapy was oral posaconazole. The second line drugs where oral therapy was unable to be administered were intravenous voriconazole (cohort 1) versus intravenous posaconazole (cohort 2). Results: There were 142 patients enrolled in the study, 71 in each cohort. The proportion of patients remaining on first-line prophylaxis or progressing to second-, third-, and fourth-line options was 22.5%, 39.4%, 29.6%, and 8.5% in cohort 1 and 39.4%, 59.2%, 1.4%, and 0% in cohort 2, respectively. The frequency of neuropsychiatric adverse events was significantly higher in cohort 1 compared to cohort 2 (49.3% vs. 19.8%, p = .0004). Occurrence of proven and probable fungal infections was not significantly different between cohorts. Antifungal drug expenditure was $359 935 (AUD) more in cohort 1 ($830 486 AUD) compared to cohort 2 ($477 149 AUD). Conclusion: The antifungal prophylaxis pathway used in cohort 2 resulted in reduced antifungal-associated adverse effects, less patients requiring progression to 3rd and 4th line prophylaxis and reduced antifungal drug costs.Philip R. Selby, Morgyn S. Warner, Sandra L. Peake, Peter Bardy, Devendra Hiwase, Deepak Singhal, Ashanka Beligaswatte, Uwe Hahn, Jason A. Roberts, David Yeung, Sepehr Shaki

Population Pharmacokinetics of Ganciclovir in Allogeneic Hematopoietic Stem Cell Transplant Patients

Treatment of cytomegalovirus (CMV) infection in allogeneic hematopoietic stem cell transplantation (alloHCT) patients with ganciclovir is complicated by toxicity and resistance. This study aimed to develop an intravenous ganciclovir population pharmacokinetic model for post-alloHCT patients and to determine dosing regimens likely to achieve suggested therapeutic exposure targets. We performed a prospective observational single-center pharmacokinetic study in adult alloHCT patients requiring treatment with intravenous ganciclovir for CMV viremia or disease. Samples were analyzed using a validated ultraperformance liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R. Twenty patients aged 18 to 69 years were included in the study. A 2-compartment model with linear elimination from the central compartment and between occasion variability best described the data. Incorporating creatinine clearance (CLCR) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and presence of continuous renal replacement therapy as covariates for ganciclovir clearance improved the model. Compared to current dosing recommendations, simulations demonstrated loading doses were required to achieve a target AUC24 of 80 to 120 mg.h/L on day 1 of induction therapy. Increased individualization of post-loading induction and maintenance doses based on CLCR is required to achieve the suggested exposures for efficacy (AUC24 >80/>40 mg.h/L for induction/maintenance) while remaining below the exposure thresholds for toxicity (AUC24 <120/<60 mg.h/L for induction/maintenance). Intravenous ganciclovir dosing in alloHCT patients can be guided by CLCR estimated by CKD-EPI. Incorporation of loading doses into induction dosing regimens should be considered for timely achievement of currently suggested exposures.Philip R. Selby, Aaron J. Heffernan, David Yeung, Morgyn S. Warner, Sandra L. Peake, Uwe Hahn, Steven C. Wallis, Brett Mcwhinney, Jacobus P. J. Ungerer, Sepehr Shakib, Jason A. Robert