524 research outputs found

    Anesthesia triggers drug delivery to experimental glioma in mice by hijacking caveolar transport

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    Abstract Background: Pharmaceutical intervention in the CNS is hampered by the shielding function of the blood-brain barrier (BBB). To induce clinical anesthesia, general anesthetics such as isoflurane readily penetrate the BBB. Here, we investigated whether isoflurane can be utilized for therapeutic drug delivery. Methods: Barrier function in primary endothelial cells was evaluated by transepithelial/transendothelial electrical resistance, and nanoscale STED and SRRF microscopy. In mice, BBB permeability was quantified by extravasation of several fluorescent tracers. Mouse models including the GL261 glioma model were evaluated by MRI, immunohistochemistry, electron microscopy, western blot, and expression analysis. Results: Isoflurane enhances BBB permeability in a time- and concentration-dependent manner. We demonstrate that, mechanistically, isoflurane disturbs the organization of membrane lipid nanodomains and triggers caveolar transport in brain endothelial cells. BBB tightness re-establishes directly after termination of anesthesia, providing a defined window for drug delivery. In a therapeutic glioblastoma trial in mice, simultaneous exposure to isoflurane and cytotoxic agent improves efficacy of chemotherapy. Conclusions: Combination therapy, involving isoflurane-mediated BBB permeation with drug administration has far-reaching therapeutic implications for CNS malignancies

    "A different world" exploring and understanding the climate of a recently re-rolled sexual offender prison

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    Understanding how sexual offenders experience prison and its environment is important because such experiences can impact on rehabilitation outcomes. The purpose of this research investigation was to explore the rehabilitative and therapeutic climate of a recently re-rolled sexual offender prison. The research took a mixed methods approach and consisted of quantitative and qualitative phases. There were differences between prisoners and staff on their perception of the prison climate and for prisoner and staff relationships. The qualitative results helped to explain the quantitative findings and added a more nuanced understanding of the experience of the prison, the nature of prisoner and staff relationships and the opportunities for personal growth within the prison. The study has important implications for prisons that co-locate sexual offenders and want to provide an environment conducive to rehabilitation

    When work keeps us apart: a thematic analysis of the experience of business travellers

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    Whilst business travel is deemed important for organizational success and economic outcomes, little is known about the actual process of business travelling from the perspective of individuals who undertake such travel on a regular basis. Thus the current qualitative study examined how business travellers (three women and eight men) attempt to find a balance between work and family, by focusing on how time together and time apart are experienced. The results can be interpreted and framed within work/family border theory in that business travellers’ borders are less defined and less permeable, thus requiring them to border-cross more frequently. This necessitates a process of negotiation with key border-keepers (their spouse/partner). Business travellers also undertake compensatory behaviours to make up for their time away from family. In order to find a work/family balance they go through a process of adapting, negotiating and tailoring their lives around their work commitments to alleviate work-life conflict

    Radial Sizing of Lipid Nanotubes Using Membrane Displacement Analysis

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    We report a novel method for the measurement of lipid nanotube radii. Membrane translocation is monitored between two nanotube-connected vesicles, during the expansion of a receiving vesicle, by observing a photobleached region of the nanotube. We elucidate nanotube radii, extracted from SPE vesicles, enabling quantification of membrane composition and lamellarity. Variances of nanotube radii were measured, showing a growth of 40-56 nm, upon increasing cholesterol content from 0 to 20%

    Intersectional identities and dilemmas in interactions with health care professionals: An interpretative phenomenological analysis of British gay Muslim men

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    Individual interviews were conducted with six self-identified Muslim gay men living in London focusing on their experience of health service use. Transcripts were analysed using Interpretative Phenomenological Analysis. Analysis identified two major themes: namely, the close(d) community and self-management with health care professionals, detailing participants’ concerns regarding the risks of disclosing sexuality; and the authentic identity: “you’re either a Muslim or you’re gay, you can’t be both”, which delineated notions of incommensurate identity. Analysis highlights the need for health practitioners to have insight into the complexity of intersectional identities, identity disclosure dynamics, and the negative = consequences of assumptions made, be these heteronormative or faith-related

    Sport coaches' experiences of athlete injury : the development and regulation of guilt

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    This study sought to examine coaches’ stories of guilt in the specific context of athlete injury. Using narrative interviews with a diverse group of ten coaches, guilt was found to be a commonly experienced emotion that the participants also sought to regulate. The coaches’ experiences of the embodiment and management of guilt is primarily, although not exclusively, interrogated using the mainstream psychological theorising of Kubany and Watson (2003). The article concludes by connecting the coaches’ experiences of guilt with critiques of the prevailing deontological approach used to define what it means to be a ‘good’ sport coach. Here we suggest that dominant perspectives in coach education may be instrumental in entrenching coaches’ experience of guilt

    On Combining Stated Preferences and Revealed Preferences Approaches to Evaluate Environmental Resources Having a Recreational Use

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    This work aims at analysing the value of recreational water uses for the Idro Lake (Lombardy, Northern Italy), which has been experiencing dramatic fluctuations in its levels in recent years, due to excessive productive withdrawal that affected recreational uses. It estimates the economic benefits deriving from recreational uses, by considering the current recreational demand and the hypothetical one obtained by considering an “improved quality” scenario. Through an on-site survey, we built a panel dataset. Following Whitehead et al. (2000) and Hanley et al. (2003) we get welfare estimates by combining SP and RP responses. The present CS is estimated in €134 per individual, whilst the increase in CS is estimated in €173 per individual. These figures can be confronted with the economic value of competitive uses and with the clean up costs, respectively, to infer some policy indications

    Feminist phenomenology and the woman in the running body

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    Modern phenomenology, with its roots in Husserlian philosophy, has been taken up and utilised in a myriad of ways within different disciplines, but until recently has remained relatively under-used within sports studies. A corpus of sociological-phenomenological work is now beginning to develop in this domain, alongside a longer standing literature in feminist phenomenology. These specific social-phenomenological forms explore the situatedness of lived-body experience within a particular social structure. After providing a brief overview of key strands of phenomenology, this article considers some of the ways in which sociological, and particularly feminist phenomenology, might be used to analyse female sporting embodiment. For illustrative purposes, data from an autophenomenographic project on female distance running are also included, in order briefly to demonstrate the application of phenomenology within sociology, as both theoretical framework and methodological approach

    “We now have a patient and not a criminal” : An exploratory study of judges and lawyers’ views on suicide attempters and the law in Ghana

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    This study explored the views of judges and lawyers of the superior courts of Ghana on the law criminalizing attempted suicide. Qualitative data were collected from 12 experienced legal practitioners of the superior courts (five judges and seven lawyers) using a semi-structured interview schedule. Thematic analysis of the data yielded three main perspectives: In defence of the Law, Advocating a Repeal, and Pro-Health Orientation. Although exploratory, the findings of this study offer cues for stepping up suicide literacy and advocacy programmes toward either a repeal of the law or a reform
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