Procedures of exclusion and reserves of inclusion in the “Public spheres”

Neste ensaio procuro problematizar o conceito da esfera pública como elaborado por Jürgen Habermas. Faço uma crítica orgânica â concepção Imaculada desta como também dos conceitos chaves do agir comunicativo e do mundo vivo. Ao mesmo tempo, quero evitar uma queda tanto em posições foucaultianas, que absolutiza a tal ponto os procedimentos de exclusão que a idéia de um agir interativo que não se submeteria aos tentáculos do poder se encontra anulada, como também em posições luhmannianas, que dessubstancializam a esfera pública ao chamá-la uma auto-tematização da sociedade. Sem querer idealizar as reservas inacabadas do projeto da modernidade (concebido como emancipação do homem através da sua razão - Kant),pleiteio uma visão da tensão entre poder e o magma do imaginário social (Castoriadis)que admite a porosidade da esfera pública como reino ambivalente: alvo de colonização por parte do poder, e, também, espaço no qual os atores sociais buscam influenciar o sistema,que se desloca cada vez mais do mundo vivo

Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning.EaStCHEM, NHS Lothian, Jamie King Cancer Research FundThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6AN01032

Targeted SERS nanosensors measure physicochemical gradients and free energy changes in live 3D tumor spheroids.

Use of multicellular tumor spheroids (MTS) to investigate therapies has gained impetus because they have potential to mimic factors including zonation, hypoxia and drug-resistance. However, analysis remains difficult and often destroys 3D integrity. Here we report an optical technique using targeted nanosensors that allows in situ 3D mapping of redox potential gradients whilst retaining MTS morphology and function. The magnitude of the redox potential gradient can be quantified as a free energy difference (ΔG) and used as a measurement of MTS viability. We found that by delivering different doses of radiotherapy to MTS we could correlate loss of ΔG with increasing therapeutic dose. In addition, we found that resistance to drug therapy was indicated by an increase in ΔG. This robust and reproducible technique allows interrogation of an in vitro tumor-model's bioenergetic response to therapy, indicating its potential as a tool for therapy development.Leverhulme Trust (Grant ID: RPG-2012-680), Jamie King Cancer Research FundThis is the final version of the article. It first appeared from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6NR06031

Selective vulnerability of tripartite synapses in Amyotrophic Lateral Sclerosis

Authors would like to acknowledge the following funders: Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), the Euan MacDonald Centre and Chief Scientist Office, The European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development grant 202932).Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. Separate lines of evidence suggest that synapses and astrocytes play a role in the pathological mechanisms underlying ALS. Given that astrocytes make specialised contacts with some synapses, called tripartite synapses, we hypothesise that tripartite synapses could act as the fulcrum of disease in ALS. To test this hypothesis, we have performed an extensive microscopy-based investigation of synapses and tripartite synapses in the spinal cord of ALS model mice and post-mortem human tissue from ALS cases. We reveal widescale synaptic changes at the early symptomatic stages of the SOD1G93a mouse model. Super-resolution microscopy reveals that large complex postsynaptic structures are lost in ALS mice. Most surprisingly, tripartite synapses are selectively lost, while non-tripartite synapses remain in equal number to healthy controls. Finally, we also observe a similar selective loss of tripartite synapses in human post-mortem ALS spinal cords. From these data we conclude that tripartite synaptopathy is a key hallmark of ALS.Publisher PDFPeer reviewe

Multi-directional dynamic model for traumatic brain injury detection

Traumatic brain injury (TBI) is a complex injury that is hard to predict and diagnose, with many studies focused on associating head kinematics to brain injury risk. Recently, there has been a push towards using computationally expensive finite element (FE) models of the brain to create tissue deformation metrics of brain injury. Here, we developed a 3 degree-of-freedom lumped-parameter brain model, built based on the measured natural frequencies of a FE brain model simulated with live human impact data, to be used to rapidly estimate peak brain strains experienced during head rotational accelerations. On our dataset, the simplified model correlates with peak principal FE strain by an R2 of 0.80. Further, coronal and axial model displacement correlated with fiber-oriented peak strain in the corpus callosum with an R2 of 0.77. Using the maximum displacement predicted by our brain model, we propose an injury criteria and compare it against a number of existing rotational and translational kinematic injury metrics on a dataset of head kinematics from 27 clinically diagnosed injuries and 887 non-injuries. We found that our proposed metric performed comparably to peak angular acceleration, linear acceleration, and angular velocity in classifying injury and non-injury events. Metrics which separated time traces into their directional components had improved deviance to those which combined components into a single time trace magnitude. Our brain model can be used in future work as a computationally efficient alternative to FE models for classifying injuries over a wide range of loading conditions.Comment: 10 figures, 3 table

Informing investment to reduce inequalities: a modelling approach

Background: Reducing health inequalities is an important policy objective but there is limited quantitative information about the impact of specific interventions. Objectives: To provide estimates of the impact of a range of interventions on health and health inequalities. Materials and methods: Literature reviews were conducted to identify the best evidence linking interventions to mortality and hospital admissions. We examined interventions across the determinants of health: a ‘living wage’; changes to benefits, taxation and employment; active travel; tobacco taxation; smoking cessation, alcohol brief interventions, and weight management services. A model was developed to estimate mortality and years of life lost (YLL) in intervention and comparison populations over a 20-year time period following interventions delivered only in the first year. We estimated changes in inequalities using the relative index of inequality (RII). Results: Introduction of a ‘living wage’ generated the largest beneficial health impact, with modest reductions in health inequalities. Benefits increases had modest positive impacts on health and health inequalities. Income tax increases had negative impacts on population health but reduced inequalities, while council tax increases worsened both health and health inequalities. Active travel increases had minimally positive effects on population health but widened health inequalities. Increases in employment reduced inequalities only when targeted to the most deprived groups. Tobacco taxation had modestly positive impacts on health but little impact on health inequalities. Alcohol brief interventions had modestly positive impacts on health and health inequalities only when strongly socially targeted, while smoking cessation and weight-reduction programmes had minimal impacts on health and health inequalities even when socially targeted. Conclusions: Interventions have markedly different effects on mortality, hospitalisations and inequalities. The most effective (and likely cost-effective) interventions for reducing inequalities were regulatory and tax options. Interventions focused on individual agency were much less likely to impact on inequalities, even when targeted at the most deprived communities