113 research outputs found
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
Negotiating queer and religious identities in higher education: queering âprogressionâ in the âuniversity experienceâ
This article addresses the negotiation of âqueer religiousâ student identities in UK higher education. The âuniversity experienceâ 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 âbackwardsâ religious homophobia as a sentiment/space/subject âoutsideâ education, this article follows the experiences and expectations of queer Christian students. In asking whether notions of âqueering higher educationâ (Rumens 2014 Rumens, N. 2014. âQueer Business: Towards Queering the Purpose of the Business School.â In The Entrepreneurial University: Public Engagements, Intersecting Impacts, edited by Y. Taylor, 82â104. Basingstoke: Palgrave Macmillan.) âfitâ with queer-identifying religious youth, the article explores how educational experiences are narrated and made sense of as âprogressiveâ. 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 âprogressiveâ and âbackwardsâ with regard to sexuality and religion need to be met with caution, where the âuniversity experienceâ can shape and shake sexual-religious identity
1-Methylnicotinamide and nicotinamide: two related anti-inflammatory agents that differentially affect the functions of activated macrophages
Panta Rhei benchmark dataset: socio-hydrological data of paired events of floods and droughts
As the adverse impacts of hydrological extremes increase in many regions of the world, a better
understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk
management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about
the processes, interactions, and feedbacks in complex humanâwater systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e. two floods
or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and
cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both
floods and droughts, in the number of cases assessed and in the quantity of socio-hydrological data. The benchmark dataset comprises (1) detailed review-style reports about the events and key processes between the two
events of a pair; (2) the key data table containing variables that assess the indicators which characterize management shortcomings, hazard, exposure, vulnerability, and impacts of all events; and (3) a table of the indicators
of change that indicate the differences between the first and second event of a pair. The advantages of the
dataset are that it enables comparative analyses across all the paired events based on the indicators of change
and allows for detailed context- and location-specific assessments based on the extensive data and reports of
the individual study areas. The dataset can be used by the scientific community for exploratory data analyses, e.g. focused on causal links between risk management; changes in hazard, exposure and vulnerability; and
flood or drought impacts. The data can also be used for the development, calibration, and validation of sociohydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al., 2023,
https://doi.org/10.5880/GFZ.4.4.2023.001)
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
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
Value-added strategies and forward integration in the Swedish sawmill industry: positioning and profitability in the high-volume segment
Interlopers in Class: A Duoethnography of Working-Class Women Academics
This paper introduces the concept of the interloper for examining classed and gendered dislocation. Focusing on academia, which we view as a classed and gendered field, we draw on Bourdieu and feminist standpoint theory to account for how we, as women of working-class origin, have experienced âbreachesâ through which we have come to understand ourselves in classed and gendered terms. Coming from different cultural backgrounds, we also reflect on how understandings of class are context-specific. We employ a duoethnographic method which emphasizes the value of subjective experiences for organizational and social analyses. The paper shows how the concept of the interloper may shed light on the dynamic, relational character of constructions of class and gender; the maintenance work that is performed; and how a sense of permanent inbetweenness characterizes our ongoing movement between the fields of the family and academia
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