414 resultados para Heams, Stacey


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In this article we build on Jones and Spicer's (2009) conceptualization of the entrepreneur as an empty signifier. We explore the function of the signifier 'entrepreneurship' within a social context marked by crisis: Ireland 2007-2010. In doing so, we show how its articulation by government acted to legitimize the continuation of market logics and, relatedly, the existing political status quo. Theoretically, we demonstrate the usefulness of Laclau and Mouffe's conception of hegemony, which shares a Lacanian legacy with Jones and Spicer. This helps us to understand the contradictory nature of the signifier of the entrepreneur in Irish political and social discourse, along with its relationship to the reproduction of political hegemony.

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Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).

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Older adults face important risky decisions about their health, their financial future, and their social environment. We examine age differences in risk-taking behaviors in multiple risk domains across the adult life span.

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BACKGROUND:
Statistical numeracy, necessary for making informed medical decisions, is reduced among older adults who make more decisions about their medical care and treatment than at any other stage of life. Objective numeracy scales are a source of anxiety among patients, heightened among older adults.
OBJECTIVE:
We investigate the subjective numeracy scale as an alternative tool for measuring statistical numeracy with older adult samples.
METHODS:
Numeracy was assessed using objective measures for 526 adults ranging in age from 18 to 93 years, and all participants provided subjective numeracy ratings.
RESULTS:
Subjective numeracy correlated highly with objective measurements among oldest adults (70+ years; r = 0.51, 95% CI 0.32, 0.66), and for younger age groups. Subjective numeracy explained 33.2% of age differences in objective numeracy.
CONCLUSION:
The subjective numeracy scale provides an effective tool for assessing statistical numeracy for broad age ranges and circumvents problems associated with objective numeracy measures.

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BACKGROUND: The need for structured education programmes for type 2 diabetes is a high priority for many governments around the world. One such national education programme in the United Kingdom is the DESMOND Programme, which has been shown to be robust and effective for patients in general. However, these programmes are not generally targeted to people with intellectual disabilities (ID), and robust evidence on their effects for this population is lacking. We have adapted the DESMOND Programme for people with ID and type 2 diabetes to produce an amended programme known as DESMOND-ID. This protocol is for a pilot trial to determine whether a large-scale randomised trial is feasible, to test if DESMOND-ID is more effective than usual care in adults with ID for self-management of their type 2 diabetes, in particular as a means to reduce glycated haemoglobin (Hb1Ac), improve psychological wellbeing and quality of life and promote a healthier lifestyle. This protocol describes the rationale, methods, proposed analysis plan and organisational and administrative details.

METHODS/DESIGN: This trial is a two arm, individually randomised, pilot trial for adults with ID and type 2 diabetes, and their family and/or paid carers. It compares the DESMOND-ID programme with usual care. Approximately 36 adults with mild to moderate ID will be recruited from three countries in the United Kingdom. Family and/or paid carers may also participate in the study. Participants will be randomly assigned to one of two conditions using a secure computerised system with robust allocation concealment. A range of data will be collected from the adults with ID (biomedical, psychosocial and self-management strategies) and from their carers. Focus groups with all the participants will assess the acceptability of the intervention and the trial.

DISCUSSION: The lack of appropriate structured education programmes and educational materials for this population leads to secondary health conditions and may lead to premature deaths. There are significant benefits to be gained globally, if structured education programmes are adapted and shown to be successful for people with ID and other cognitive impairments.

TRIAL REGISTRATION: Registered with International Standard Randomised Controlled Trial (identifier: ISRCTN93185560 ) on 10 November 2014.

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The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/eIF2α/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression.

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An ultrathin layer of metasurface that almost completely annihilates the reflection of light (>99.5%) over a wide range of incident angles (>80°) is experimentally demonstrated. Such zero-reflectance metafilms exhibit optimal performance for plasmonic sensing, since their sensitivity to changes of local refractive index is far superior to films of nonzero reflectance. Since both main detection mechanisms tracking intensity changes and wavelength shifts are improved, zero-reflectance metafilms are optimal for localized surface plasmon resonance molecular sensing. Such nanostructures have significant opportunities in many areas, including enhanced light harvesting as well as in developing high-performance molecular sensors for a wide range of chemical and biomedical applications.

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In this paper, a novel nanolens with super resolution, based on the photon nanojet effect through dielectric nanostructures in visible wavelengths, is proposed. The nanolens is made from plastic SU-8, consisting of parallel semi-cylinders in an array. This paper focuses on the lens designed by numerical simulation with the finite-difference time domain method and nanofabrication of the lens by grayscale electron beam lithography combined with a casting/bonding/lift-off transfer process. Monte Carlo simulation for injected charge distribution and development modeling was applied to define the resultant 3D profile in PMMA as the template for the lens shape. After the casting/bonding/lift-off process, the fabricated nanolens in SU-8 has the desired lens shape, very close to that of PMMA, indicating that the pattern transfer process developed in this work can be reliably applied not only for the fabrication of the lens but also for other 3D nanopatterns in general. The light distribution through the lens near its surface was initially characterized by a scanning near-field optical microscope, showing a well defined focusing image of designed grating lines. Such focusing function supports the great prospects of developing a novel nanolithography based on the photon nanojet effect.

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This book, written when Walker was Visiting Professor at the Technical University Munich in 2011, describes his research on the effects of digital technology on architectural design and construction, and on the development of ‘digital craft’. The primary example given is The Swarm, a digitally designed and manufactured pavilion, produced with students while Walker was at TU Munich. It now stands outside the Bayerischen Architektenkammer (Bavarian Chamber of Architects) in Munich. Through such research-by-design, Walker asks larger questions: what can designers craft without a master craftsman’s skills, and how can craft skills be recovered through digital fabrication? Another example in the book is the Swoosh Pavilion, one of two public-space-scale architectural pavilion prototypes Walker developed between 2008 and 2009 at the Architectural Association (AA), using applied digital modelling and CNC techniques to investigate methods of teaching and testing digital processes through making. Swoosh (2008) and a second AA pavilion, Driftwood (2009), were discussed by Walker and Martin Self, his co-investigator, in ‘Fractal, bad hair, Swoosh and Driftwood pavilions of Intermediate Unit 2, 2006–2009’, published in the AD reader, Manufacturing the Bespoke (2012), which includes essays by well-known critics and designers such as Mathias Kohler and Michael Stacey. Both AA pavilions were sponsored by FinnForest Merk, Arup, HOK and Building Design Magazine, and were seen by large international audiences in Bedford Square, London during the 2008–9 ‘AA Projects Review’ shows. The book Making Pavilions (Walker and Self, AA Agenda No. 9, Architectural Association Press, 2011) also discusses their work over seven years of teaching at the Architectural Association. At the same time, Walker collaborated on a series of Serpentine pavilions, commissioned annually by the Serpentine Gallery, London, co-designing these experimental structures with internationally renowned architects Daniel Libeskind, Oscar Niemeyer, Toyo Ito and Alvaro Siza.

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Shared decision-making (SDM) is a high priority in healthcare policy and is complementary to the recovery philosophy in mental health care. This agenda has been operationalised within the Values-Based Practice (VBP) framework, which offers a theoretical and practical model to promote democratic interprofessional approaches to decision-making. However, these are limited by a lack of recognition of the implications of power implicit within the mental health system. This study considers issues of power within the context of decision-making and examines to what extent decisions about patients? care on acute in-patient wards are perceived to be shared. Focus groups were conducted with 46 mental health professionals, service users, and carers. The data were analysed using the framework of critical narrative analysis (CNA). The findings of the study suggested each group constructed different identity positions, which placed them as inside or outside of the decision-making process. This reflected their view of themselves as best placed to influence a decision on behalf of the service user. In conclusion, the discourse of VBP and SDM needs to take account of how differentials of power and the positioning of speakers affect the context in which decisions take place.

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Thesis (Master's)--University of Washington, 2016-03

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The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against Salmonella was unclear. Here, we demonstrate that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL-1β production during acute peritoneal challenge in vivo. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon NLRC4 inflammasome activation. The resistance of neutrophils to pyroptotic death is unique among inflammasome-signaling cells so far described and allows neutrophils to sustain IL-1β production at a site of infection without compromising the crucial inflammasome-independent antimicrobial effector functions that would be lost if neutrophils rapidly lysed upon caspase-1 activation. Inflammasome pathway modification in neutrophils thus maximizes host proinflammatory and antimicrobial responses during pathogen challenge.

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Although it is widely assumed that temperature affects pollutant toxicity, few studies have actually investigated this relationship. Moreover, such research as has been done has involved constant temperatures; circumstances which are rarely, if ever, actually experienced by north temperate, littoral zone cyprinid species. To investigate the effects of temperature regime on nickel toxicity in goldfish (Carassius auratus L.), 96- and 240-h LCSO values for the heavy metal pollutant, nickel (NiCI2.6H20), were initially determined at 2DoC (22.8 mg/L and 14.7 mg/L in artificially softened water). Constant temperature bioassays at 10°C, 20°C and 30°C were conducted at each of 0, 240-h and 96-h LCSO nickel concentrations for 240 hours. In order to determine the effects of temperature variation during nickel exposure it was imperative that the effects of a single temperature change be investigated before addressing more complex regimes. Single temperature changes of + 10°C or -10°C were imposed at rates of 2°C/h following exposures of between 24 hand 216 h. The effects of a single temperature change on mortality, and duration of toxicant exposure at high and low temperatures were evaluated. The effects of fluctuating temperatures during exposure were investigated through two regimes. The first set of bioassays imposed a sinewave diurnal cycle temperature (20.±.1DOC) throughout the 10 day exposure to 240-h LeSO Ni. The second set of investigations approximated cyprinid movement through the littoral zone by imposing directionally random temperature changes (±2°C at 2-h intervals), between extremes of 10° and 30°C, at 240-h LC50 Ni. Body size (i.e., total length, fork length, and weight) and exposure time were recorded for all fish mortalities. Cumulative mortality curves under constant temperature regimes indicated significantly higher mortality as temperature and nickel concentration were increased. At 1DOC no significant differences in mortality curves were evident in relation to low and high nickel test concentrations (Le., 16 mg/L and 20 mg/L). However at 20°C and 30°C significantly higher mortality was experienced in animals exposed to 20 mg/L Ni. Mortality at constant 10°C was significantly lower than at 30°C with 16 mg/L and was significantly loWer than each of 2DoC and 39°C tanks at 20 mg/L Ni exposure. A single temperature shift from 20°C to 1DoC resulted in a significant decrease in mortality rate and conversely, a single temperature shift from 20°C to 30°C resulted in a significant increase in mortality rate. Rates of mortality recorded during these single temperature shift assays were significantly different from mortality rates obtained under constant temperature assay conditions. Increased Ni exposure duration at higher temperatures resulted in highest mortality. Diurnally cycling temperature bioassays produced cumulative mortality curves approximating constant 20°C curves, with increased mortality evident after peaks in the temperature cycle. Randomly fluctuating temperature regime mortality curves also resembled constant 20°C tanks with mortalities after high temperature exposures (25°C - 30°C). Some test animals survived in all assays with the exception of the 30°C assays, with highest survival associated with low temperature and low Ni concentration. Post-exposure mortality occurred most frequently in individuals which had experienced high Ni concentrations and high temperatures during assays. Additional temperature stress imposed 2 - 12 weeks post exposure resulted in a single death out of 116 individuals suggesting that survivors are capable of surviving subsequent temperature stresses. These investigations suggest that temperature significantly and markedly affects acute nickel toxicity under both constant and fluctuating temperature regimes and plays a role in post exposure mortality and subsequent stress response.