Closure, credence and rationality: a problem for non-belief hinge epistemology

Duncan Pritchard’s Epistemic Angst promises a novel solution to the closure-based sceptical problem that, unlike more traditional solutions, does not entail revising our fundamental epistemological commitments. In order to do this, it appeals to a Wittgensteinian account of rational evaluation, the overarching theme of which is that it neither makes sense to doubt nor to believe in our anti-sceptical hinge commitments. The purpose of this paper is to show that the argument for the claim that there can be no rational basis to believe our anti-sceptical hinge commitments relies upon an implicit assumption about rational support that I label The Pritchensteinian Rational Grounds Principle. I argue that, insofar as this principle is intended to apply to closure-style inferences, it leads to irrational doxastic attitudes. I consider a seemingly plausible modification of the principle that would avoid this result but show that this modified principle faces serious problems of its own

To Regulate or Not: Fiji's Social Media

This In Brief seeks to document the proposed plans for curtailing the ‘excesses’ of social media and challenges some of the ongoing claims related to social media. Additionally, it discusses some possible policy considerations for protecting freedom of speech in social media in Fiji and the wider Pacific.AusAI

Aerodynamic design guidelines and computer program for estimation of subsonic wind tunnel performance

General guidelines are given for the design of diffusers, contractions, corners, and the inlets and exits of non-return tunnels. A system of equations, reflecting the current technology, has been compiled and assembled into a computer program (a user's manual for this program is included) for determining the total pressure losses. The formulation presented is applicable to compressible flow through most closed- or open-throat, single-, double-, or non-return wind tunnels. A comparison of estimated performance with that actually achieved by several existing facilities produced generally good agreement

To Regulate or Not: Fiji’s Social Media

This In Brief seeks to document the proposed plans for curtailing the ‘excesses’ of social media and challenges some of the ongoing claims related to social media. Additionally, it discusses some possible policy considerations for protecting freedom of speech in social media in Fiji and the wider Pacific

Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders

The mood disorders major depressive disorder and bipolar disorder are prevalent, are inadequately treated, and little is known about their etiologies. A better understanding of the causes of mood disorders would benefit from improved animal models of mood disorders, which now rely on behavioral measurements. This review considers the limitations in relating measures of rodent behaviors to mood disorders, and the evidence from behavioral assessments indicating that glycogen synthase kinase-3 (GSK3) dysregulation promotes mood disorders and is a potential target for treating mood disorders. The classical mood stabilizer lithium was identified by studying animal behaviors and later was discovered to be an inhibitor of GSK3. Several mood-relevant behavioral effects of lithium in rodents have been identified, and most have now been shown to be due to its inhibition of GSK3. An extensive variety of pharmacological and molecular approaches for manipulating GSK3 are discussed, the results of which strongly support the proposal that inhibition of GSK3 reduces both depression-like and manic-like behaviors. Studies in human postmortem brain and peripheral cells also have identified correlations between alterations in GSK3 and mood disorders. Evidence is reviewed that depression may be associated with impaired inhibitory control of GSK3, and mania by hyper-stimulation of GSK3. Taken together, these studies provide substantial support for the hypothesis that inhibition of GSK3 activity is therapeutic for mood disorders. Future research should identify the causes of dysregulated GSK3 in mood disorders and the actions of GSK3 that contribute to these diseases

Religion and the new media: discourses and debates in the 2018 Fiji General Election Campaign

This article explores discourses and debates on secularism, religion, and politics in social media in connection with the 2018 Fiji general election campaign, and in interviews with leading figures in churches and religious organisations. It discusses how people responded to these issues. It shows that there is still a pervasive lack of clarity in the Fijian population as to what the terms Christian state, secular state, secularism, and secularisation mean, how people understand, discuss, and debate them, and how this lack of clarity was used politically during the campaign

Glycogen Synthase Kinase-3: A Promising Therapeutic Target for Fragile X Syndrome

Recent advances in understanding the pathophysiological mechanisms contributing to fragile X syndrome (FXS) have increased optimism that drug interventions can provide significant therapeutic benefits. FXS results from inadequate expression of functional fragile X mental retardation protein (FMRP). FMRP may have several functions, but it is most well-established as an RNA binding protein that regulates translation, and it is thought that by this mechanism FMRP is capable of affecting numerous cellular processes by selectively regulating protein levels. The multiple cellular functions regulated by FMRP suggest that multiple interventions may be required for reversing the effects of deficient FMRP. Evidence that inhibitors of glycogen synthase kinase-3 (GSK3) may contribute to the therapeutic treatment of FXS is reviewed here. Lithium, a GSK3 inhibitor, improved function in the Drosophila model of FXS. In mice lacking FMRP expression (FX mice), GSK3 is hyperactive in several brain regions. Significant improvements in several FX-related phenotypes have been obtained in FX mice following the administration of lithium, and in some case other GSK3 inhibitors. These responses include normalization of heightened audiogenic seizure susceptibility and of hyperactive locomotor behavior, enhancement of passive avoidance learning retention and of sociability behaviors, and corrections of macroorchidism, neuronal spine density, and neural plasticity measured electrophysiologically as long term depression. A pilot clinical trial of lithium in patients with FXS also found improvements in several measures of behavior. Taken together, these findings indicate that lithium and other inhibitors of GSK3 are promising candidate therapeutic agents for treating FXS

GSK3β N-terminus binding to p53 promotes its acetylation

The prevalence in human cancers of mutations in p53 exemplifies its crucial role as a tumor suppressor transcription factor. Previous studies have shown that the constitutively active serine/threonine kinase glycogen synthase kinase-3β (GSK3β) associates with the C-terminal basic domain of p53 and regulates its actions. In this study we identified the GSK3β N-terminal amino acids 78–92 as necessary for its association with p53. Inhibitors of GSK3 impaired the acetylation of p53 at Lys373 and Lys382 near the GSK3β binding region in p53, indicating that GSK3β facilitates p53 acetylation. We also found that acetylation of p53 reduced its association with GSK3β, as well as with GSK3α. These results indicate that the N-terminal region of GSK3β binds p53, this association promotes the acetylation of p53, and subsequently acetylated p53 dissociates from GSK3

Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence bas

Fiji Flag Change: Social Media Responds

This In Brief seeks to discuss and assess the public social media responses from the two main social media sites that were publicised by the Fijian government, for public feedback on the flag change proposal.AusAI