746 research outputs found
A Mathematical Model of Communication with Reputational Concerns
We investigate a mathematical model where an expert advises a decision maker for two periods. The decision maker is initially unsure about whether the expert is biased or not. After consulting the expert on the decision problem of period one, the decision maker updates belief about the expert’s bias and consults the expert on the problem of period two. We find that more information is delivered in the model’s first period than in the one-period situation of communication
Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats
The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity
The Glauber model and flow analysis with Pb-Pb collisions at =2.76 TeV
This work presents data analysis on Pb-Pb collisions at =2.76 TeV with centrality . We present introduction and
Monte-Carlo simulation results of the Glauber model, which shed light on the
initial geometric configuration of heavy ion collisions. Three-dimensional
correlation function is plotted, and Fourier decomposition is carried out in
order to obtain elliptic flow. Based on the assumption that non-flow effect is
less prominent in long-range area, we separate it from the second Fourier
decomposition of two-particle correlation function by making polynomial curve
fitting.Comment: 10 pages,8 figures, revisions are made, accepted by ICAPM 2022
Conference Proceeding
Engaging Stigmatised Communities in Australia with Digital Health Systems: Towards Data Justice in Public Health
Introduction: In 2018, following government policy changes to Australia’s national electronic health record system, ‘My Health Record’, consumer advocates—including organisations representing people living with HIV, people who use drugs and sex workers—raised concerns about privacy and data security. Responding to these controversies, this study explores the practical, ethical and political complexities of engaging stigmatised communities with digital health systems. Methods: We conducted 16 qualitative semi-structured interviews in 2020 with key informants representing communities who experience stigma, discrimination and marginalisation in Australia. These communities included people living with HIV, sex workers, people who inject drugs, gay and bisexual men and transgender and gender diverse people. We conducted a reflexive thematic analysis. Results: Key informants were sceptical of proposed benefits of electronic health records for their communities, and concerned about privacy risks and the potential for discrimination. Meaningful consultation, consent mechanisms and tackling structural stigma were raised as solutions for engaging communities. Conclusions: Although communities could benefit from being included in digital health systems, significant cultural, legal and social reforms from government were believed to be necessary to build trust in digital health systems. We argue that these forms of data justice are necessary for effective future systems. Policy Implications: Engaging stigmatised communities—including in relation to gender, sexuality, sex work, drug use, HIV—requires a commitment to data justice. The design and implementation of digital health systems requires investment in ongoing and meaningful consultation with communities and representative organisations
Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials
BACKGROUND:
Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo.
METHODS:
We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated.
RESULTS:
Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth.
CONCLUSION:
It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations
Spawning rings of exceptional points out of Dirac cones
The Dirac cone underlies many unique electronic properties of graphene and
topological insulators, and its band structure--two conical bands touching at a
single point--has also been realized for photons in waveguide arrays, atoms in
optical lattices, and through accidental degeneracy. Deformations of the Dirac
cone often reveal intriguing properties; an example is the quantum Hall effect,
where a constant magnetic field breaks the Dirac cone into isolated Landau
levels. A seemingly unrelated phenomenon is the exceptional point, also known
as the parity-time symmetry breaking point, where two resonances coincide in
both their positions and widths. Exceptional points lead to counter-intuitive
phenomena such as loss-induced transparency, unidirectional transmission or
reflection, and lasers with reversed pump dependence or single-mode operation.
These two fields of research are in fact connected: here we discover the
ability of a Dirac cone to evolve into a ring of exceptional points, which we
call an "exceptional ring." We experimentally demonstrate this concept in a
photonic crystal slab. Angle-resolved reflection measurements of the photonic
crystal slab reveal that the peaks of reflectivity follow the conical band
structure of a Dirac cone from accidental degeneracy, whereas the complex
eigenvalues of the system are deformed into a two-dimensional flat band
enclosed by an exceptional ring. This deformation arises from the dissimilar
radiation rates of dipole and quadrupole resonances, which play a role
analogous to the loss and gain in parity-time symmetric systems. Our results
indicate that the radiation that exists in any open system can fundamentally
alter its physical properties in ways previously expected only in the presence
of material loss and gain
Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations
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by/4.0
FRA2A is a CGG repeat expansion associated with silencing of AFF3
Folate-sensitive fragile sites (FSFS) are a rare cytogenetically visible subset of dynamic mutations. Of the eight molecularly characterized FSFS, four are associated with intellectual disability (ID). Cytogenetic expression results from CGG tri-nucleotide-repeat expansion mutation associated with local CpG hypermethylation and transcriptional silencing. The best studied is the FRAXA site in the FMR1 gene, where large expansions cause fragile X syndrome, the most common inherited ID syndrome. Here we studied three families with FRA2A expression at 2q11 associated with a wide spectrum of neurodevelopmental phenotypes. We identified a polymorphic CGG repeat in a conserved, brain-active alternative promoter of the AFF3 gene, an autosomal homolog of the X-linked AFF2/FMR2 gene: Expansion of the AFF2 CGG repeat causes FRAXE ID. We found that FRA2A-expressing individuals have mosaic expansions of the AFF3 CGG repeat in the range of several hundred repeat units. Moreover, bisulfite sequencing and pyrosequencing both suggest AFF3 promoter hypermethylation. cSNP-analysis demonstrates monoallelic expression of the AFF3 gene in FRA2A carriers thus predicting that FRA2A expression results in functional haploinsufficiency for AFF3 at least in a subset of tissues. By whole-mount in situ hybridization the mouse AFF3 ortholog shows strong regional expression in the developing brain, somites and limb buds in 9.5-12.5dpc mouse embryos. Our data suggest that there may be an association between FRA2A and a delay in the acquisition of motor and language skills in the families studied here. However, additional cases are required to firmly establish a causal relationship
Geometric aspects of space-time reflection symmetry in quantum mechanics
For nearly two decades, much research has been carried out on properties of physical systems described by Hamiltonians that are not Hermitian in the conventional sense, but are symmetric under space-time reflection; that is, they exhibit PT symmetry. Such Hamiltonians can be used to model the behavior of closed quantum systems, but they can also be replicated in open systems for which gain and loss are carefully balanced, and this has been implemented in laboratory experiments for a wide range of systems. Motivated by these ongoing research activities, we investigate here a particular theoretical aspect of the subject by unraveling the geometric structures of Hilbert spaces endowed with the parity and time-reversal operations, and analyze the characteristics ofPT -symmetric Hamiltonians. A canonical relation between aPT -symmetric operator and a Hermitian operator is established in a geometric setting. The quadratic form corresponding to the parity operator, in particular, gives rise to a natural partition of the Hilbert space into two halves corresponding to states having positive and negative PT norm. Positive definiteness of the norm can be restored by introducing a conjugation operator C ; this leads to a positive-definite inner product in terms of CPT conjugation
Expanding the phenotype in argininosuccinic aciduria: need for new therapies
OBJECTIVES: This UK-wide study defines the natural history of argininosuccinic aciduria and compares long-term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia-lowering drugs. METHODS: Retrospective analysis of medical records prior to March 2013, then prospective analysis until December 2015. Blinded review of brain MRIs. ASL genotyping. RESULTS: Fifty-six patients were defined as early-onset (n = 23) if symptomatic < 28 days of age, late-onset (n = 23) if symptomatic later, or selectively screened perinatally due to a familial proband (n = 10). The median follow-up was 12.4 years (range 0-53). Long-term outcomes in all groups showed a similar neurological phenotype including developmental delay (48/52), epilepsy (24/52), ataxia (9/52), myopathy-like symptoms (6/52) and abnormal neuroimaging (12/21). Neuroimaging findings included parenchymal infarcts (4/21), focal white matter hyperintensity (4/21), cortical or cerebral atrophy (4/21), nodular heterotopia (2/21) and reduced creatine levels in white matter (4/4). 4/21 adult patients went to mainstream school without the need of additional educational support and 1/21 lives independently. Early-onset patients had more severe involvement of visceral organs including liver, kidney and gut. All early-onset and half of late-onset patients presented with hyperammonaemia. Screened patients had normal ammonia at birth and received treatment preventing severe hyperammonaemia. ASL was sequenced (n = 19) and 20 mutations were found. Plasma argininosuccinate was higher in early-onset compared to late-onset patients. CONCLUSIONS: Our study further defines the natural history of argininosuccinic aciduria and genotype-phenotype correlations. The neurological phenotype does not correlate with the severity of hyperammonaemia and plasma argininosuccinic acid levels. The disturbance in nitric oxide synthesis may be a contributor to the neurological disease. Clinical trials providing nitric oxide to the brain merit consideration
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