Pharmacokinetic and behavioral characterization of a longterm antipsychotic delivery system in rodents and rabbits

Rationale: Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems. Objectives: The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits. Materials and methods: Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits. Results: Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits. Conclusions: The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations

Bromoform and dibromomethane above the Mauritanian upwelling: Atmospheric distributions and oceanic emissions

Natural sources of bromoform (CHBr3) and dibromomethane (CH2Br2), including oceanic emissions, contribute to stratospheric and tropospheric O3 depletion. Convective transport over tropical oceans could deliver large amounts of these short-lived organic bromine species to the upper atmosphere. High mixing ratios of atmospheric CHBr3 in air masses from the northwest African coast have been hypothesized to originate from the biologically active Mauritanian upwelling. During a cruise into the upwelling source region in spring 2005 the atmospheric mixing ratios of the brominated compounds CHBr3 and CH2Br2 were found to be elevated above the marine background and comparable to measurements in other coastal regions. The shelf waters were identified as a source of both compounds for the atmosphere. The calculated sea-to-air emissions support the hypothesis of a strong upwelling source for reactive organic bromine. However, calculated emissions were not sufficient to explain the elevated concentrations observed in the coastal atmosphere. Other strong sources that could contribute to the large atmospheric mixing ratios previously observed over the Atlantic Ocean must exist within or near West Africa

Negotiating queer and religious identities in higher education: queering ‘progression’ in the ‘university experience’

This article addresses the negotiation of ‘queer religious’ student identities in UK higher education. The ‘university experience’ has generally been characterised as a period of intense transformation and self-exploration, with complex and overlapping personal and social influences significantly shaping educational spaces, subjects and subjectivities. Engaging with ideas about progressive tolerance and becoming, often contrasted against ‘backwards’ religious homophobia as a sentiment/space/subject ‘outside’ education, this article follows the experiences and expectations of queer Christian students. In asking whether notions of ‘queering higher education’ (Rumens 2014 Rumens, N. 2014. “Queer Business: Towards Queering the Purpose of the Business School.” In The Entrepreneurial University: Public Engagements, Intersecting Impacts, edited by Y. Taylor, 82–104. Basingstoke: Palgrave Macmillan.) ‘fit’ with queer-identifying religious youth, the article explores how educational experiences are narrated and made sense of as ‘progressive’. Educational transitions allow (some) sexual-religious subjects to negotiate identities more freely, albeit with ongoing constraints. Yet perceptions of what, where and who is deemed ‘progressive’ and ‘backwards’ with regard to sexuality and religion need to be met with caution, where the ‘university experience’ can shape and shake sexual-religious identity

Oceanic bromoform sources for the tropical atmosphere

Oceanic bromoform (CHBr3) is the major source of organic Br to the atmosphere and may be significant for ozone depletion through the contribution of reactive bromine to the upper troposphere and lower stratosphere of the midlatitudes and tropics. We report the first analyses of boundary layer air, surface and deep ocean waters from the tropical Atlantic. The data provide evidence of a source of CHBr3 throughout the tropical open ocean associated with the deep chlorophyll maximum within the tropical thermocline. Equatorial upwelling carries the CHBr3 to the surface, adding to increased concentrations in the equatorial mixed layer and driving oceanic emissions that support locally elevated atmospheric concentrations. In air masses that had crossed the coastal upwelling region off NW Africa even higher atmospheric mixing ratios were measured. The observations suggest a link between climate, wind-driven upwelling, and the supply of Br to the upper atmosphere of the tropics

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186.Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78 center dot 6%] female patients and 4922 [21 center dot 4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1 center dot 4 [IQR 0 center dot 6-3 center dot 4]) compared with the prepandemic phase (2 center dot 0 [0 center dot 9-3 center dot 7]; p<0 center dot 0001) and pandemic decrease phase (2 center dot 3 [1 center dot 0-5 center dot 0]; p<0 center dot 0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69 center dot 0%] of 3704 vs 1515 [71 center dot 5%] of 2119; OR 1 center dot 1 [95% CI 1 center dot 0-1 center dot 3]; p=0 center dot 042), lymph node metastases (343 [9 center dot 3%] vs 264 [12 center dot 5%]; OR 1 center dot 4 [1 center dot 2-1 center dot 7]; p=0 center dot 0001), and tumours at high risk of structural disease recurrence (203 [5 center dot 7%] of 3584 vs 155 [7 center dot 7%] of 2006; OR 1 center dot 4 [1 center dot 1-1 center dot 7]; p=0 center dot 0039).Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation.Funding None.Copyright (c) 2023 Published by Elsevier Ltd. All rights reserved