Austerity for Whom?

In contrast to the recent multi-billion dollar bailouts offered to leading sectors of capital, fiscal austerity is poised to make a comeback worldwide. Labour will be forced to pay for the public debt accumulated in the aftermath of the recent global financial and economic crisis. Notwithstanding change and evolution in the neoliberal model over time, this return to austerity is consistent with overall policy in the neoliberal period which can be considered an era of permanent restraint in most areas of social spending. This article examines a variety of trends that have emerged over the past thirty years of neoliberal rule: the various facets of neoliberal policy and their temporal dimensions; as well as the results of market-reliance and spending reforms: growing affluence for a minority of Canadians while the majority lose ground and inequalities are further entrenched. Asking 'austerity for whom' directs attention at the interconnections between affluence and austerity that exist in Canada. Contrairement aux récents plans de sauvetage impliquant des milliards de dollars offerts aux principaux secteurs de l’économie, l'austérité budgétaire s’apprête à faire un retour à l’échelle planétaire. Les travailleurs n’auront d’autre choix que de rembourser la dette publique engendrée à la suite de la récente crise économique et financière mondiale. Malgré le changement et l'évolution dans le modèle néo-libéral au fil du temps, ce retour à l'austérité concorde avec la politique globale de la période néolibérale pouvant être considérée comme une époque de restrictions permanentes touchant la plupart des domaines de dépenses sociales. Cet article examine une série de tendances ayant émergé au cours des trente dernières années du pouvoir néo-libéral: les différents aspects de la politique néolibérale et leurs dimensions temporelles, ainsi que les résultats du recours au marché financier et de la réforme du contrôle de la dépense: forte croissance d'une minorité de Canadiens alors que la majorité perd du terrain enracinant davantage les inégalités. La question « l’austérité pour qui? » dirige l’attention vers l’interconnexion entre l’affluence et l’austérité qui existent au Canada

Canada's Reluctant Acceptance of the Colombo Plan for Co-operative Economic Development in South and South-East Asia

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Impulsivity-related cognition in alcohol dependence: is it moderated by DRD2/ANKK1 gene status and executive dysfunction?

Perceived impaired control over alcohol use is a key cognitive construct in alcohol dependence that has been related prospectively to treatment outcome and may mediate the risk for problem drinking conveyed by impulsivity in non-dependent drinkers. The aim of the current study was to investigate whether perceived impaired control may mediate the association between impulsivity-related measures (derived from the Short-form Eysenck Personality Questionnaire Revised) and alcohol-dependence severity in alcohol-dependent drinkers. Furthermore, the extent to which this hypothesized relationship was moderated by genetic risk (Taq1A polymorphism in the DRD2/ANKK1 gene cluster) and verbal fluency as an indicator of executive cognitive ability (Controlled Oral Word Association Test) was also examined. A sample of 143 alcohol-dependent inpatients provided an extensive clinical history of their alcohol use, gave 10 ml of blood for DNA analysis, and completed self-report measures relating to impulsivity, impaired control and severity of dependence. As hypothesized, perceived impaired control (partially) mediated the association between impulsivity-related measures and alcohol-dependence severity. This relationship was not moderated by the DRD2/ANICK1 polymorphism or verbal fluency. These results suggest that, in alcohol dependence, perceived impaired control is a cognitive mediator of impulsivity-related constructs that may be unaffected by DRD2/ANKK1 and neurocognitive processes underlying the retrieval of verbal information. (C) 2014 Elsevier Ltd. All rights reserved

What are the research priorities in dance for dementia? A co-created agenda to support equitable research

Background: There is a gap in the field of dance for dementia regarding how to engage in and improve equitable, moral, and rights-based ways of working with those with lived experience to co-design research priorities. We set out to create a collaborative research agenda for this field. Methods: A series of collaborative activities were conducted, including an in-person workshop (n = 59 people), online workshop (n = 23 people), digital communications, podcasts, and co-writing, including with people living with dementia (PLWD), health and social care professionals, artists, arts organisational representatives, and academic researchers. Results: Three key themes were constructed: 1) Improving access to dance participation; 2) Prioritising co-produced approaches; and 3) Enabling innovation in measurement and methods. Conclusion: This is the first co-produced agenda for the field of dance for dementia. Underpinned by diverse perspectives and lived experience, it outlines themes and associated research questions that can be used in future research.</p

A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general

Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes

The sorting and assembly machinery (SAM) Complex is responsible for assembling β‐barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block‐face‐scanning electron microscopy and computer‐assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50‐ deficient myotubes from mice and humans with wild‐type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography‐Mass Spectrometry‐based metabolomics to explore differential changes in WT and Sam50‐deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50‐deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß‐ Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50‐deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50‐deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly