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The paper begins with an overview of the ways in which the concept of 'social exclusion' has been employed in both academic and political and media discourse. In the context of 'race' and housing, the term is most often seen in debates about inequalities between majority and minority communities. These inequalities form the basis of the next two sections of the paper: the first dealing with the national evidence, the second with a case study of Bradford District. The paper then looks at how the academic literature has traditionally theorised these inequalities, and asks whether the exclusion paradigm adds anything of value to these debates. It is concluded that whilst the concept may well be of use in drawing attention in policy circles to questions of inequality, it is rather less worthwhile in the context of sociological debates. It has tended to be used in numerous disparate senses thus potentially obscuring (rather then clarifying) issues, is little more than a descriptive label, and has lent itself to a form of sloganeering which may stifle rather than encourage debate.
\n \n\n \n \nWith a few notable exceptions planning analysts have been rather slower to recognise the very difficult issues raised by a polyethnic community. Much of the recent literature has tended to focus on 'excluded' individuals and communities, or even 'excluded' neighbourhoods. This paper will argue that it is vitally important for the future of our urban areas to address the policy and practice dimensions of both inequality and difference. The purpose of the present article is to provoke debate, and to dispel some popular myths and stereotypes which plague much of current policy making and implementation. Owing to its brevity, it will not be possible to delve into some of the more complex nuances. It will, however, point out where the key questions arise, and where to look for possible solutions. As such, it is intended as a contribution to the debate about cultural and ethnicity-sensitive service delivery. In order to sharpen the analysis, it focuses in particular on one set of interrelated issues: namely, housing policy and household projections.
\n \n\n \n \nThe data on which this paper is based comes from an international study of \u2018Perceptions of Europe\u2019 sponsored in 1990 by the Polish Association for the Club of Rome in Warsaw. In all, twelve countries throughout Asia, the Middle East, North and South America, Europe, and Australia participated. \u00a9 1992, Taylor & Francis Group, LLC. All rights reserved.
\n \n\n \n \nMichael Banton's paper provides fascinating insights into his long-running intellectual disagreements with John Rex, the other major post-war figure in the sociology of \u2018race relations\u2019. Published work and personal recollections are supplemented by a series of communications by letter to flesh out the precise nature of these debates. They reveal differing views on the ontological status of \u2018race\u2019, race relations and racism, as well as a number of criticisms of Rex's work. He argues that Rex was wrong to put so much faith in the ability of classical sociology to address these concerns, and that there was a disjuncture between theory, methods and substance in his empirical work. There is also a suggestion that Rex played down the significance of racism. The greatest difference between them, however, lay in their divergent views on the role of sociology and the sociologist.
\n \n\n \n \nThere are few sociology texts that acquire truly seminal status. This brief paper, however, reflects on one of the most celebrated and often cited works in British urban sociology. It seeks to explain: (1) the book's initial impact on debates and research in the field of \u2018race and ethnic relations\u2019; (2) the key controversies sparked by its theoretical positioning; and (3) why, and in what ways, it remains of relevance almost half a century after it was written. It concludes that there are two reasons for its continued appeal and significance. First, it placed housing firmly at the centre of debates about the position of Britain's migrant communities; second, it illustrates the potential of sociological research. At a time when controversies rage about \u2018impact\u2019, here is a work that not only contributed to our theoretical understanding of contemporary society, but also illustrated the value of \u2018public sociology\u2019 by engaging with the polity to bring about social change.
\n \n\n \n \nThis book makes a forthright case for a shift in policy focus from 'community cohesion' to the broader notion of social cohesion, and is distinctive and innovative in its focus on evaluation. It constitutes an extremely valuable source both for practitioners involved in social cohesion interventions and for researchers and students studying theory-based evaluation and the policy areas highlighted (housing, intergenerational issues, the recession, education, communications, community development).
\n \n\n \n \nThis paper explores the notion of 'ethnic group' focussing, in particular, on attempts to transform the concept into an empirical indicator in population censuses. The latter is seen to be riven with difficulties, not least the fact that such measures tend to be attempting to address two conflicting agendas - one requiring an ascriptive, the other a subjective, measure. Illustrating the core arguments with the decennial census in Britain, the paper explores the contested political terrain underpinning the introduction of such a question, and then demonstrates that the construction of an 'ethnic group' indicator takes the form of a complex dialectical process involving negotiation and re-negotiation on the part of a myriad of social actors and structural forces at macro-, meso- and micro-levels. Finally, it reflects on broader concerns arising from the reification of the measure, not least its material effects in the context of debates and policies on 'multiculturalism'. \u00a9 2013 Copyright Taylor and Francis Group, LLC.
\n \n\n \n \nAlzheimer's disease (AD) is an age-related neurodegenerative condition and the most common type of dementia, characterised by pathological accumulation of extracellular plaques and intracellular neurofibrillary tangles that mainly consist of amyloid-\u03b2 (A\u03b2) and hyperphosphorylated tau aggregates, respectively. Previous studies in mouse models with a targeted knock-out of the microtubule-associated protein tau (Mapt) gene demonstrated that A\u03b2-driven toxicity is tau-dependent. However, human cellular models with chronic tau lowering remain unexplored. In this study, we generated stable tau-depleted human induced pluripotent stem cell (iPSC) isogenic panels from two healthy individuals using CRISPR-Cas9 technology. We then differentiated these iPSCs into cortical neurons in vitro in co-culture with primary rat cortical astrocytes before conducting electrophysiological and imaging experiments for a wide range of disease-relevant phenotypes. Both AD brain derived and recombinant A\u03b2 were used in this study to elicit toxic responses from the iPSC-derived cortical neurons. We showed that tau depletion in human iPSC-derived cortical neurons caused considerable reductions in neuronal activity without affecting synaptic density. We also observed neurite outgrowth impairments in two of the tau-depleted lines used. Finally, tau depletion protected neurons from adverse effects\u00a0by mitigating the impact of exogenous A\u03b2-induced hyperactivity, deficits in retrograde axonal transport of mitochondria, and neurodegeneration. Our study established stable human iPSC isogenic panels with chronic tau depletion from two healthy individuals. Cortical neurons derived from these iPSC lines showed that tau is essential in A\u03b2-driven hyperactivity, axonal transport deficits, and neurodegeneration, consistent with studies conducted in Mapt-/- mouse models. These findings highlight the protective effects of chronic tau lowering strategies in AD pathogenesis and reinforce the potential in clinical settings. The tau-depleted human iPSC models can now be applied at scale to investigate the involvement of tau in disease-relevant pathways and cell types.
\n \n\n \n \nIdentifying factors that are causes of disease progression, especially in neurodegenerative diseases, is of considerable interest. Disease progression can be described as a trajectory of outcome over time-for example, a linear trajectory having both an intercept (severity at time zero) and a slope (rate of change). A technique for identifying causal relationships between one exposure and one outcome in observational data whilst avoiding bias due to confounding is two sample Mendelian Randomisation (2SMR). We consider a multivariate approach to 2SMR using a multilevel model for disease progression to estimate the causal effect an exposure has on the intercept and slope. We carry out a simulation study comparing a na\u00efve univariate 2SMR approach to a multivariate 2SMR approach with one exposure that effects both the intercept and slope of an outcome that changes linearly with time since diagnosis. The simulation study results, across six different scenarios, for both approaches were similar with no evidence against a non-zero bias and appropriate coverage of the 95% confidence intervals (for intercept 93.4-96.2% and the slope 94.5-96.0%). The multivariate approach gives a better joint coverage of both the intercept and slope effects. We also apply our method to two Parkinson's cohorts to examine the effect body mass index has on disease progression. There was no strong evidence that BMI affects disease progression, however the confidence intervals for both intercept and slope were wide.
\n \n\n \n \nThe International Parkinson and Movement Disorder Society (MDS) created a task force (TF) to provide a critical overview of the Parkinson's disease (PD) subtyping field and develop a guidance on future research in PD subtypes. Based on a literature review, we previously concluded that PD subtyping requires an ultimate alignment with principles of precision medicine, and consequently novel approaches were needed to describe heterogeneity at the individual patient level. In this manuscript, we present a novel purpose-driven framework for subtype research as a guidance to clinicians and researchers when proposing to develop, evaluate, or use PD subtypes. Using a formal consensus methodology, we determined that the key purposes of PD subtyping are: (1) to predict disease progression, for both the development of therapies (use in clinical trials) and prognosis counseling, (2) to predict response to treatments, and (3) to identify therapeutic targets for disease modification. For each purpose, we describe the desired product and the research required for its development. Given the current state of knowledge and data resources, we see purpose-driven subtyping as a pragmatic and necessary step on the way to precision medicine. \u00a9 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
\n \n\n \n \nCongenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women.
\n \n\n \n \nIron deficiency is the most prevalent micronutrient disorder globally. When severe, iron deficiency leads to anemia, which can be deleterious to cardiac function. Given the central role of iron and oxygen in cardiac biology, multiple pathways are expected to be altered in iron-deficiency anemia, and identifying these requires an unbiased approach. To investigate these changes, gene expression and metabolism were studied in mice weaned onto an iron-deficient diet for 6 weeks. Whole-exome transcriptomics (RNAseq) identified over 1,500 differentially expressed genes (DEGs), of which 22% were upregulated and 78% were downregulated in the iron-deficient group, relative to control animals on an iron-adjusted diet. The major biological pathways affected were oxidative phosphorylation and pyruvate metabolism, as well as cardiac contraction and responses related to environmental stress. Cardiac metabolism was studied functionally using in vitro and in vivo methodologies. Spectrometric measurement of the activity of the four electron transport chain complexes in total cardiac lysates showed that the activities of Complexes I and IV were reduced in the hearts of iron-deficient animals. Pyruvate metabolism was assessed in vivo using hyperpolarized 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate. Hearts from iron-deficient and anemic animals showed significantly decreased flux through pyruvate dehydrogenase and increased lactic acid production, consistent with tissue hypoxia and induction of genes coding for glycolytic enzymes and H+-monocarboxylate transport-4. Our results show that iron-deficiency anemia results in a metabolic remodeling toward a glycolytic, lactic acid-producing phenotype, a hallmark of hypoxia.
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