362 research outputs found

    The relationship between cognitive variables and offending behaviour in adults with intellectual disabilities : a systematic review

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    Background Interventions for offenders with intellectual disabilities (ID) have used cognitive variables as measures of treatment outcome. However, the relevance of cognitive variables to offending in people with intellectual disabilities is unclear. This review aimed to evaluate the evidence for a relationship between cognitive variables and offending in people with intellectual disabilities. Method A systematic search identified studies comparing offenders and non‐offenders with intellectual disabilities on an aspect of cognition. Seven cognitive variables were found and compared across 15 studies. These were appraised for their quality using an adapted quality appraisal checklist. The reliability and validity of cognitive measures were also considered. Results and conclusions Other than for cognitive distortions, the evidence for a relationship between cognitive variables and offending in people with intellectual disabilities is currently limited due to methodological weaknesses and the small number of studies assessing each variable. Clinicians are advised to focus on cognitive distortions until better evidence is available

    Protoporphyrin IX Fluorescence Contrast in Invasive Glioblastomas is Linearly Correlated with Gd Enhanced Magnetic Resonance Image Contrast but has Higher Diagnostic Accuracy

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    The sensitivity and specificity of in vivo magnetic resonance (MR) imaging is compared with production of protoporphyrin IX (PpIX), determined ex vivo, in a diffusely infiltrating glioma. A human glioma transfected with green fluorescent protein, displaying diffuse, infiltrative growth, was implanted intracranially in athymic nude mice. Image contrast from corresponding regions of interest (ROIs) in in vivo MR and ex vivo fluorescence images was quantified. It was found that all tumor groups had statistically significant PpIX fluorescence contrast and that PpIX contrast demonstrated the best predictive power for tumor presence. Contrast from gadolinium enhanced T1-weighted (T1W+Gd) and absolute T2 images positively predicted the presence of a tumor, confirmed by the GFP positive (GFP+) and hematoxylin and eosin positive (H&E+) ROIs. However, only the absolute T2 images had predictive power from controls in ROIs that were GFP+ but H&E negative. Additionally, PpIX fluorescence and T1W+Gd image contrast were linearly correlated in both the GFP+ (r = 0.79, p\u3c1×10−8) and H&E+ (r = 0.74, p\u3c0.003) ROIs. The trace diffusion images did not have predictive power or significance from controls. This study indicates that gadolinium contrast enhanced MR images can predict the presence of diffuse tumors, but PpIX fluorescence is a better predictor regardless of tumor vascularity

    What do you think this is? "Conceptual uncertainty" in geoscience interpretation

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    Interpretations of seismic images are used to analyze sub-surface geology and form the basis for many exploration and extraction decisions, but the uncertainty that arises from human bias in seismic data interpretation has not previously been quantified. All geological data sets are spatially limited and have limited resolution. Geoscientists who interpret such data sets must, therefore, rely upon their previous experience and apply a limited set of geological concepts. We have documented the range of interpretations to a single data set, and in doing so have quantified the �conceptual uncertainty� inherent in seismic interpretation. In this experiment, 412 interpretations of a synthetic seismic image were analyzed. Only 21% of the participants interpreted the �correct� tectonic setting of the original model, and only 23% highlighted the three main fault strands in the image. These results illustrate that conceptual uncertainty exists, which in turn explains the large range of interpretations that can result from a single data set. We consider the role of prior knowledge in biasing individuals in their interpretation of the synthetic seismic section, and our results demonstrate that conceptual uncertainty has a critical influence on resource exploration and other areas of geoscience. Practices should be developed to minimize the effects of conceptual uncertainty, and it should be accounted for in risk analysis

    Maximising transparency in a doctoral thesis: The complexities of writing about the use of QSR*NVIVO within a grounded theory study

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    This paper discusses the challenges of how to provide a transparent account of the use of the software programme QSR*NVIVO (QSR 2000) within a Grounded Theory framework (Glaser and Strauss 1967; Strauss and Corbin 1998). Psychology students are increasingly pursuing qualitative research projects such to the extent that the UK Economic and Social Research Council (ESRC) advise that students should have skill in the use of computer assisted qualitative data analysis software (CAQDAS) (Economic and Social Research Council 2001). Unlike quantitative studies, rigid formulae do not exist for writing-up qualitative projects for doctoral theses. Most authors, however, agree that transparency is essential when communicating the findings of qualitative research. Sparkes (2001) recommends that evaluative criteria for qualitative research should be commensurable with the aims, objectives, and epistemological assumptions of the research project. Likewise, the use of CAQDAS should vary according to the research methodology followed, and thus researchers should include a discussion of how CAQDAS was used. This paper describes how the evolving process of coding data, writing memos, categorising, and theorising were integrated into the written thesis. The structure of the written document is described including considerations about restructuring and the difficulties of writing about an iterative process within a linear document

    Imaging of Glioma Tumor with Endogenous Fluorescence Tomography

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    Tomographic imaging of a glioma tumor with endogenous fluorescence is demonstrated using a noncontact single-photon counting fan-beam acquisition system interfaced with microCT imaging. The fluorescence from protoporphyrin IX (PpIX) was found to be detectable, and allowed imaging of the tumor from within the cranium, even though the tumor presence was not visible in the microCT image. The combination of single-photon counting detection and normalized fluorescence to transmission detection at each channel allowed robust imaging of the signal. This demonstrated use of endogenous fluorescence stimulation from aminolevulinic acid (ALA) and provides the first in vivo demonstration of deep tissue tomographic imaging with protoporphyrin IX. Fluorescence tomography provides a tool for preclinical molecular contrast agent assessment in oncology.1, 2, 3, 4 Systems have advanced in complexity to where noncontact imaging,5 automated boundary recovery,6 and sophisticated internal tissue shapes can be included in the recovered images. The translation of this work to humans will require molecular contrast agents that are amenable to regulatory approval and maintain tumor specificity in humans, where often nonspecific uptake of molecular imaging agents can decrease their utility. In this study, a new fluorescence tomography system coupled to microCT7 was used to illustrate diagnostic detection of orthotopic glioma tumors that were not apparent in the microCT images, using endogenous fluorescent contrast from protoporphyrin IX (PpIX). Glioma tumors provide significant endogenous fluorescence from PpIX,8, 9, 10, 11 and this is enhanced when the subject imaged has been administered aminolevulinic acid (ALA). The endogenous production process of PpIX is known to stem from the administered, ALA bypassing the regulatory inhibition of ALA synthase, allowing the heme synthesis pathway to proceed uninhibited. Since there is a limited supply of iron in the body, this process produces overabundance of PpIX rather than heme, and many tumors have been shown to have high yields of PpIX. Clinical trials with PpIX fluorescence guided resection of tumors have shown significant promise,12 and yet deep tissue imaging with PpIX fluorescence has not been exploited in clinical use. Early studies have shown that detection of these tumors with PpIX is feasible,13, 14 but no tomographic imaging has been used. This limitation in development has largely been caused by problems in wavelength filtering and low signal intensity, as well as background fluorescence from the skin limiting sensitivity to deeper structures. In the system developed and used here, this feasibility is demonstrated by imaging a human xenograft glioma model. To solve the sensitivity problem and study the ability to diagnostically image PpIX in vivo, time-correlated single-photon counting was used in the fluorescence tomography system, which provides maximum sensitivity. Figure 1a shows the system designed to match up with a microCT, allowing both x-ray structural and optical functional imaging sequentially. Lens-coupled detection of signals is acquired from the mouse using five time-resolved photomultiplier tubes (H7422P-50, Hamamatsu, Japan) with single-photon counting electronics (SPC-134 modules, Becker and Hickl GmbH, Germany). The system has fan-beam transmission geometry similar to a standard CT scanner, with single source delivery of a1-mW role= presentation \u3e1-mW pulsed diode laser light at 635nm role= presentation \u3e635nm , collimated to a 1-mm role= presentation \u3e1-mm effective area on the animal. The five detection lenses were arranged in an arc, each with 22.5-deg role= presentation \u3e22.5-deg angular separation, centered directly on the opposite side of the animal with long working distance pickup,7 allowing noncontact measurement of the diffuse light through the animal. The diffuse intensity signals collected at each of the five channels were then translated via 400-μm role= presentation \u3e400-μm fibers and split using beamsplitters to be directed toward the fluorescence (95%) and transmission (5%) channel detectors. A 650-nm role= presentation \u3e650-nm long-pass filter was used in the fluorescence channels to isolate the signal, and in the transmitted intensity signals, a neutral density filter (2 OD) was used to attenuate the signals. This latter filtering was necessary to ensure that the fluorescence and transmission. Intensity signals fell within the same dynamic range, allowing a single 1s role= presentation \u3e1s acquisition for each detector. Scans were then performed by rotating the fan-beam around the specimen to 32 locations. A GE eXplore Locus SP scanner (GE Healthcare, London, Ontario, Canada) that incorporated a detector with 94-micronpixel role= presentation \u3e94-micronpixel resolution, a 80-kV role= presentation \u3e80-kV peak voltage, and a tube current of 450μAs role= presentation \u3e450μAs , was used in acquiring the microCT data, as displayed in Fig. 2 . In this example, since soft tissue was being imaged, the CT data was largely used to image the exterior of the animal, although in future studies, it could be used to isolate the cranium region as well

    The Ternary Rab27a–Myrip–Myosin VIIa Complex Regulates Melanosome Motility in the Retinal Pigment Epithelium

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    The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a–Myrip–MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery

    How User‐centric Innovation is Affecting Stakeholder Marketing Strategies: Exploratory Findings from the Music Industry

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    This paper empirically explores how user‐centric innovation (UCI) in the music industry is affecting how key stakeholder groups are approaching and developing their marketing (and associated management) strategies. The three‐stage interview‐based research methodology consisted of 52 semi‐structured in‐depth interviews with UCI experts and artist managers, as well as representatives from major record labels. The findings make four substantial contributions to theory and practice in the interrelated fields of UCI, marketing and the music industry. First, they provide practical and pragmatic insights for industry practitioners on how different UCI marketing approaches are affecting their management strategies. Second, they take steps towards answering many of the identified gaps in research and knowledge relating to the concept of UCI. Third, they present theoretical models as a foundation for which new UCI marketing theory can be built upon. Last, they offer directions for future research to advance our empirical findings.</jats:p

    N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

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    N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P<0.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P<0.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis
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