380 research outputs found
The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake
We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms
A need for the standardization of the pharmaceutical sector in Libya
Medicines are health technologies that can translate into tangible benefits for numerous acute as well as chronic health conditions. A nation's pharmaceutical sector needs to be appropriately structured and managed in order to ensure a safe, effective and quality supply of medicines to society. The process of medicines management involves the sequential management of five critical activity areas; namely; registration, selection, procurement, distribution and use. Formalized and standardized management of all five critical activity areas positively influences the availability, quality and affordability of medicines and ultimately increases the reliability and quality of the national healthcare system
Withdrawal-induced delirium associated with a benzodiazepine switch: a case report
<p>Abstract</p> <p>Introduction</p> <p>Introduced in the early 1960s, diazepam remains among the most frequently prescribed benzodiazepine-type sedatives and hypnotics. Patients with chronic use of short-acting benzodiazepines are frequently switched to diazepam because the accumulating, long-acting metabolite, N-desmethyl-diazepam, prevents benzodiazepine-associated withdrawal symptoms, which can occur during trough plasma levels of short-acting benzodiazepines. Although mild to moderate withdrawal symptoms are frequently observed during benzodiazepine switching to diazepam, severe medical complications associated with this treatment approach have thus far not been reported.</p> <p>Case presentation</p> <p>A 64-year-old female Caucasian with major depression, alcohol dependence and benzodiazepine dependence was successfully treated for depression and, after lorazepam-assisted alcohol detoxification, was switched from lorazepam to diazepam to facilitate benzodiazepine discontinuation. Subsequent to the benzodiazepine switch, our patient unexpectedly developed an acute delirious state, which quickly remitted after re-administration of lorazepam. A newly diagnosed early form of mixed dementia, combining both vascular and Alzheimer-type lesions, was found as a likely contributing factor for the observed vulnerability to benzodiazepine-induced withdrawal symptoms.</p> <p>Conclusion</p> <p>Chronic use of benzodiazepines is common in the elderly and a switch to diazepam often precedes benzodiazepine discontinuation trials. However, contrary to common clinical practice, benzodiazepine switching to diazepam may require cross-titration with slow tapering of the first benzodiazepine to allow for the build-up of N-desmethyl-diazepam, in order to safely prevent severe withdrawal symptoms. Alternatively, long-term treatment with low doses of benzodiazepines may be considered, especially in elderly patients with chronic use of benzodiazepines and proven vulnerability to benzodiazepine-associated withdrawal symptoms.</p
Finite-size and correlation-induced effects in Mean-field Dynamics
The brain's activity is characterized by the interaction of a very large
number of neurons that are strongly affected by noise. However, signals often
arise at macroscopic scales integrating the effect of many neurons into a
reliable pattern of activity. In order to study such large neuronal assemblies,
one is often led to derive mean-field limits summarizing the effect of the
interaction of a large number of neurons into an effective signal. Classical
mean-field approaches consider the evolution of a deterministic variable, the
mean activity, thus neglecting the stochastic nature of neural behavior. In
this article, we build upon two recent approaches that include correlations and
higher order moments in mean-field equations, and study how these stochastic
effects influence the solutions of the mean-field equations, both in the limit
of an infinite number of neurons and for large yet finite networks. We
introduce a new model, the infinite model, which arises from both equations by
a rescaling of the variables and, which is invertible for finite-size networks,
and hence, provides equivalent equations to those previously derived models.
The study of this model allows us to understand qualitative behavior of such
large-scale networks. We show that, though the solutions of the deterministic
mean-field equation constitute uncorrelated solutions of the new mean-field
equations, the stability properties of limit cycles are modified by the
presence of correlations, and additional non-trivial behaviors including
periodic orbits appear when there were none in the mean field. The origin of
all these behaviors is then explored in finite-size networks where interesting
mesoscopic scale effects appear. This study leads us to show that the
infinite-size system appears as a singular limit of the network equations, and
for any finite network, the system will differ from the infinite system
Protocol of trans-Tasman feasibility randomised controlled trial of the Younger Women's Wellness After Breast Cancer (YWWACP) lifestyle intervention.
BACKGROUND: Younger women (defined as those < 50 years who are likely pre-menopausal at time of diagnosis) with breast cancer often experience persistent treatment-related side effects that adversely affect their physical and psychological wellbeing. The Women's Wellness After Cancer Program (WWACP) was adapted and piloted in Australia to address these outcomes in younger women. The aims of this feasibility study are to determine (1) the potential to translate the Younger WWACP (YWWACP) intervention to a broader population base in Aotearoa/New Zealand and Australia, and (2) the potential for success of a larger, international, phase ΙΙΙ, randomised controlled trial. METHODS: This bi-national, randomised, single-blinded controlled trial involves two main study sites in Aotearoa/New Zealand (Kōwhai study) and Australia (EMERALD study). Young women aged 18 to 50 years who completed intensive treatment (surgery, chemotherapy, and/or radiotherapy) for breast cancer in the previous 24 months are eligible. The potential to translate the YWWACP to women in these two populations will be assessed according to several feasibility outcomes. These include examining intervention accessibility, acceptability and uptake; intervention sustainability and adherence; the prevalence components of the intervention in the control group; intervention efficacy; participants' perception of measurement burden; the effectiveness of planned recruitment strategies; and trial methods and procedures. The studies collectively aim to enrol 60 participants in the intervention group and 60 participants in the control group (total = 120 participants). DISCUSSION: Ethical approval has been received from the Southern Health and Disability Ethics Committee (Kōwhai ref: 19/STH/215), and UnitingCare Human Research Ethics Committee (EMERALD ref: 202103). This study will provide important data on the feasibility of the refined YWWACP in the trans-Tasman context. This study will account for and harmonise cross-country differences to ensure the success of a proposed international grant application for a phase ΙΙΙ randomised controlled trial of this program to improve outcomes in younger women living with breast cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): Kōwhai ACTRN12620000260921 , registered on 27 February 2020. EMERALD ACTRN12621000447853 , registered on 19 April 2021
Neural field models with threshold noise
The original neural field model of Wilson and Cowan is often interpreted as the averaged behaviour of a network of switch like neural elements with a distribution of switch thresholds, giving rise to the classic sigmoidal population firing-rate function so prevalent in large scale neuronal modelling. In this paper we explore the effects of such threshold noise without recourse to averaging and show that spatial correlations can have a strong effect on the behaviour of waves and patterns in continuum models. Moreover, for a prescribed spatial covariance function we explore the differences in behaviour that can emerge when the underlying stationary distribution is changed from Gaussian to non-Gaussian. For travelling front solutions, in a system with exponentially decaying spatial interactions, we make use of an interface approach to calculate the instantaneous wave speed analytically as a series expansion in the noise strength. From this we find that, for weak noise, the spatially averaged speed depends only on the choice of covariance function and not on the shape of the stationary distribution. For a system with a Mexican-hat spatial connectivity we further find that noise can induce localised bump solutions, and using an interface stability argument show that there can be multiple stable solution branches
The dynamics of neural fields on bounded domains: an interface approach for Dirichlet boundary conditions
Continuum neural field equations model the large scale spatio-temporal dynamics of interacting neurons on a cortical surface. They have been extensively studied, both analytically and numerically, on bounded as well as unbounded domains. Neural field models do not require the specification of boundary conditions. Relatively little attention has been paid to the imposition of neural activity on the boundary, or to its role in inducing patterned states. Here we redress this imbalance by studying neural field models of Amari type (posed on one- and two-dimensional bounded domains) with Dirichlet boundary conditions. The Amari model has a Heaviside nonlinearity that allows for a description of localised solutions of the neural field with an interface dynamics. We show how to generalise this reduced but exact description by deriving a normal velocity rule for an interface that encapsulates boundary effects. The linear stability analysis of localised states in the interface dynamics is used to understand how spatially extended patterns may develop in the absence and presence of boundary conditions. Theoretical results for pattern formation are shown to be in excellent agreement with simulations of the full neural field model. Furthermore, a numerical scheme for the interface dynamics is introduced and used to probe the way in which a Dirichlet boundary condition can limit the growth of labyrinthine structures
Language and social/emotional problems identified at a universal developmental assessment at 30 months
Non peer reviewedPublisher PD
Working Memory Cells' Behavior May Be Explained by Cross-Regional Networks with Synaptic Facilitation
Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1) persistent fixed-frequency elevated rates above baseline, 2) elevated rates that decay throughout the tasks memory period, 3) rates that accelerate throughout the delay, and 4) patterns of inhibited firing (below baseline) analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex
Testing foundations of quantum mechanics with photons
The foundational ideas of quantum mechanics continue to give rise to
counterintuitive theories and physical effects that are in conflict with a
classical description of Nature. Experiments with light at the single photon
level have historically been at the forefront of tests of fundamental quantum
theory and new developments in photonics engineering continue to enable new
experiments. Here we review recent photonic experiments to test two
foundational themes in quantum mechanics: wave-particle duality, central to
recent complementarity and delayed-choice experiments; and Bell nonlocality
where recent theoretical and technological advances have allowed all
controversial loopholes to be separately addressed in different photonics
experiments.Comment: 10 pages, 5 figures, published as a Nature Physics Insight review
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