185 research outputs found

    Experiences of unemployment and formal and informal employment brokers among emerging/young adults : a socio-ecological perspective

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    This study explores the experiences and constructions of both youths and employment brokers regarding youth unemployment. Unemployed youths are defined as young people aged 17–25 looking for work. The methodology comprised qualitative methods (semi-structured interviews and a thematic analysis). A total of 17 youths and 14 organisational brokers were interviewed. The results were analysed through the lens of Bronfenbrenner’s (2007) socio-ecological model, which accounts for how influences on health can occur at different levels of the social environment, and which conceptualises health and wellbeing as existing within multiple nested ecosystems. A thematic analysis of youths’ accounts of unemployment and employment describes a number of themes at several levels of the model. The themes identified include the impact of unemployment on mental health, the development of vocational identity, positive and negative experiences in the family setting, the impact of the educational setting and its influence on the transition to employment, negative experiences with employers, and housing and transport barriers. These accounts are compared with brokers accounts of youth unemployment and their response to the young people. The key themes in brokers’ accounts highlight the importance of mental wellbeing and vocational awareness, responses to youths who had dropped out of school, the impact of intergenerational unemployment and housing barriers, the attitudes of employers toward unemployed youths, and cultural awareness in brokerage. The findings illustrate that the main areas of convergence in the youths’ and brokers’ accounts were on the issues of housing, employer experiences and importance of support during the school years immediately prior to entering the workforce. The results support previous findings on the mental health impacts of unemployment and highlight the role of identity and youth transition processes, the role of social support among unemployed youths in wellbeing, and identify the unique role of flexible learning options for the support of unemployed youths. They also highlight the role of transport and housing within the context of the participants, located in Western Sydney, chosen specifically for its larger geographical area and its higher rates of unemployment compared to the rest of Sydney. The research extends these approaches by illustrating how they apply to the issue of employment, within the structural influences of the employment service provider system in Australia and appropriately in the specific social and cultural context of Western Sydney

    Fathers and Sons: American Blues and British Rock Music, 1960-1970

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    This dissertation examines the unique cultural phenomenon of British blues-based rock music in the 1960s. It provides answers to two important questions of trans-Atlantic intellectual and cultural history. First, this dissertation will provide answers to two questions. First, it interrogates how and why African-American blues music became so popular amongst a segment of young, primarily middle-class men in Great Britain. It maps out "blues trade routes"--that is, the methods by which the music was transmitted to Britain. It explains the enthusiasm shown by young male Britishers largely in terms of their alienation from, and dissatisfaction with, mainstream British masculinity. Seen in this light, the "adoption" of African-American bluesmen as replacement "fathers" can be seen as an attempt to fill a perceived cultural need. This dissertation will also examine how these young British men, having formed bands to perform their own music, began in the mid-1960s to branch out from the blues. In a developing dialogue with like-minded bands from the United States, bands such as the Rolling Stones and Yardbirds started combining the lessons of the blues with other cultural influences such as jazz, classical music and English folk. The resulting cultural bricolage innovated popular music on both sides of the Atlantic from the 1970s onward. The dissertation draws on a variety of primary sources, including the popular music press, published interviews with key musicians, and, of course, the recorded music itself. Fathers and Sons uses the development of popular music to address issues that have traditionally been central to the study of ideas and cultures. These include: the role of interpersonal relationships in disseminating ideas and culture; the impact of distance and proximity in impelling cultural innovation; the occurrences of bursts of creativity in distinct places at distinct times; and the ways in which gender and sexual identity are performed and negotiated through mass consumer culture. These are salient issues with which intellectual and cultural historians have dealt for decades. Thus, Fathers and Sons seeks a broader audience than merely that which would be interested in American blues, British rock music, or both

    Mapping the DNA Damaging Effects of Polypyridyl Copper Complexes with DNA Electrochemical Biosensors

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    Several classes of copper complexes are known to induce oxidative DNA damage that mediates cell death. These compounds are potentially useful anticancer agents and detailed investigation can reveal the mode of DNA interaction, binding strength, and type of oxidative lesion formed. We recently reported the development of a DNA electrochemical biosensor employed to quantify the DNA cleavage activity of the well-studied [Cu(phen)2]2+ chemical nuclease. However, to validate the broader compatibility of this sensor for use with more diverse—and biologically compatible—copper complexes, and to probe its use from a drug discovery perspective, analysis involving new compound libraries is required. Here, we report on the DNA binding and quantitative cleavage activity of the [Cu(TPMA)(N,N)]2+ class (where TPMA = tris-2-pyridylmethylamine) using a DNA electrochemical biosensor. TPMA is a tripodal copper caging ligand, while N,N represents a bidentate planar phenanthrene ligand capable of enhancing DNA interactions through intercalation. All complexes exhibited electroactivity and interact with DNA through partial (or semi-) intercalation but predominantly through electrostatic attraction. Although TPMA provides excellent solution stability, the bulky ligand enforces a non-planar geometry on the complex, which sterically impedes full interaction. [Cu(TPMA)(phen)]2+ and [Cu(TPMA)(DPQ)]2+ cleaved 39% and 48% of the DNA strands from the biosensor surface, respectively, while complexes [Cu(TPMA)(bipy)]2+ and [Cu(TPMA)(PD)]2+ exhibit comparatively moderate nuclease efficacy (ca. 26%). Comparing the nuclease activities of [Cu(TPMA)(phen)] 2+ and [Cu(phen)2]2+ (ca. 23%) confirms the presence of TPMA significantly enhances chemical nuclease activity. Therefore, the use of this DNA electrochemical biosensor is compatible with copper(II) polypyridyl complexes and reveals TPMA complexes as a promising class of DNA damaging agent with tuneable activity due to coordinated ancillary phenanthrene ligands

    Click and Cut: a click chemistry approach to developing oxidative DNA damaging agents

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    Metallodrugs provide important first-line treatment against various forms of human cancer. To overcome chemotherapeutic resistance and widen treatment possibilities, new agents with improved or alternative modes of action are highly sought after. Here, we present a click chemistry strategy for developing DNA damaging metallodrugs. The approach involves the development of a series of polyamine ligands where three primary, secondary or tertiary alkyne-amines were selected and \u27clicked\u27 using the copper-catalysed azide-alkyne cycloaddition reaction to a 1,3,5-azide mesitylene core to produce a family of compounds we call the \u27Tri-Click\u27 (TC) series. From the isolated library, one dominant ligand (TC1) emerged as a high-affinity copper(II) binding agent with potent DNA recognition and damaging properties. Using a range of in vitro biophysical and molecular techniques-including free radical scavengers, spin trapping antioxidants and base excision repair (BER) enzymes-the oxidative DNA damaging mechanism of copper-bound TC1 was elucidated. This activity was then compared to intracellular results obtained from peripheral blood mononuclear cells exposed to Cu(ll)-TC1 where use of BER enzymes and fluorescently modified dNTPs enabled the characterisation and quantification of genomic DNA lesions produced by the complex. The approach can serve as a new avenue for the design of DNA damaging agents with unique activity profiles

    Development of a nationally agreed core clinical dataset for childhood onset uveitis

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    BACKGROUND: Childhood onset uveitis comprises a group of rare inflammatory disorders characterized by clinical heterogeneity, chronicity, and uncertainties around long term outcomes. Standardized, detailed datasets with harmonized clinical definitions and terminology are needed to enable the clinical research necessary to stratify disease phenotype and interrogate the putative determinants of health outcomes. We aimed to develop a core routine clinical collection dataset for clinicians managing children with uveitis, suitable for multicenter and national clinical and experimental research initiatives. METHODS: Development of the dataset was undertaken in three phases: phase 1, a rapid review of published datasets used in clinical research studies; phase 2, a scoping review of disease or drug registries, national cohort studies and core outcome sets; and phase 3, a survey of members of a multicenter clinical network of specialists. Phases 1 and 2 provided candidates for a long list of variables for the dataset. In Phase 3, members of the UK's national network of stakeholder clinicians who manage childhood uveitis (the Pediatric Ocular Inflammation Group) were invited to select from this long-list their essential items for the core clinical dataset, to identify any omissions, and to support or revise the clinical definitions. Variables which met a threshold of at least 95% agreement were selected for inclusion in the core clinical dataset. RESULTS: The reviews identified 42 relevant studies, and 9 disease or drug registries. In total, 138 discrete items were identified as candidates for the long-list. Of the 41 specialists invited to take part in the survey, 31 responded (response rate 78%). The survey resulted in inclusion of 89 data items within the final core dataset: 81 items to be collected at the first visit, and 64 items at follow up visits. DISCUSSION: We report development of a novel consensus core clinical dataset for the routine collection of clinical data for children diagnosed with non-infectious uveitis. The development of the dataset will provide a standardized approach to data capture able to support observational clinical studies embedded within routine clinical care and electronic patient record capture. It will be validated through a national prospective cohort study, the Uveitis in childhood prospective national cohort study (UNICORNS)

    Limited Utility of Keratic Precipitate Morphology as an Indicator of Underlying Diagnosis in Ocular Inflammation

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    Objectives: We aimed to establish the degree of consensus among clinicians on descriptors of KP morphology.// Methods: A web-based exercise in which respondents associated KP descriptors, as identified through a scoping review of the published literature, to images from different disorders. Inter-observer agreement was assessed using the Krippendorff kappa alpha metric.// Results: Of the 76 descriptive terms identified by the scoping review, the most used included “mutton-fat” (n = 93 articles, 36%), “fine/dust” (n = 76, 29%), “stellate” (n = 40, 15%), “large” (n = 33, 12%), and “medium” (n = 33, 12%). The survey of specialists (n = 26) identified inter-observer agreement for these descriptors to be poor (“stellate,” kappa: 0.15, 95% confidence interval 0.13–0.17), limited (“medium”: 0.27, 95% CI 0.25–0.29; “dust/fine”: 0.36, 95% CI 0.34–0.37), or moderate (“mutton fat”: 0.40, 95% CI 0.36–0.43; “large”: 0.43, 95% CI 0.39–0.46).// Conclusion: The clinical utility of KP morphology as an indicator of disease classification is limited by low inter-observer agreement./

    UNICORNS: Uveitis in childhood prospective national cohort study protocol

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    Background: Childhood uveitis is a rare inflammatory eye disease which is typically chronic, relapsing-remitting in nature, with an uncertain aetiology (idiopathic). Visual loss occurs due to structural damage caused by uncontrolled inflammation. Understanding of the determinants of long term outcome is lacking, including the predictors of therapeutic response or how to define disease control. Aims: To describe disease natural history and outcomes amongst a nationally representative group of children with non-infectious uveitis, describe the impact of disease course on quality of life for both child and family, and identify determinants of adverse visual, structural and developmental outcomes. Methods: UNICORNS is a prospective longitudinal multicentre cohort study of children newly diagnosed with uveitis about whom a core minimum clinical dataset will be collected systematically. Participants and their families will also complete patient-reported outcome measures annually from recruitment. The association of patient (childand treatment- dependent) characteristics with outcome will be investigated using logistic and ordinal regression models which incorporate adjustment for within-child correspondence between eyes for those with bilateral disease and repeated outcomes measurement. Discussion: Through this population based, prospective longitudinal study of childhood uveitis, we will describe the characteristics of childhood onset disease. Early (1-2 years following diagnosis) outcomes will be described in the first instance, and through the creation of a national inception cohort, longer term studies will be enabled of outcome for affected children and families

    Copper(II) Complexes of Coumarin-Derived Schiff Bases and their anti-Candida Activity

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    The condensation of 7-amino-4-methyl-coumarin (1) with a number of substituted salicylaldehydes yielded a series of Schiff bases (2a–2k) in good yields. Subsequent reaction of these ligands with copper( II) acetate yielded Cu(II) complexes (3a–3k) and some were characterised using X-ray crystallography. All of the free ligands and their metal complexes were tested for their anti-Candida activity
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