893 research outputs found

    Heterogeneity in Disordered Gambling: Decision-Making and Impulsivity in Gamblers Grouped by Preferred Form.

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    Background: Previous research has indicated that disordered gamblers display deficits in impulsivity and risky decision-making, compared to healthy control groups. However, disordered gamblers are not a homogenous group, and differences in performance on neurocognitive tasks may be related to the form of gambling in which an individual chooses to engage. The present study used neurocognitive tasks and questionnaire measures to ascertain group differences in gamblers grouped by preferred form of gambling. Method: Treatment-seeking pathological gamblers from the National Problem Gambling Clinic, London (n = 101), completed a neurocognitive assessment comprising the Cambridge gamble task (CGT), the stop-signal task (SST), a probabilistic reversal learning task (PRL), and the Kirby Monetary Choice Questionnaire, as well as questionnaire measures of gambling severity, impulsivity, depression, and anxiety. Analyses compared gamblers who favored fixed-odds betting terminals (FOBTs) (the modal form) to gamblers who preferred other forms of gambling (non-FOBT). Results: The FOBT group showed impaired decision-making under risk on the CGT compared to the non-FOBT group, choosing the likely option less on more uncertain decisions. The FOBT group made fewer perseverative errors on the PRL task, had lower depression and anxiety scores, and were less likely to have a family history of problem gambling than the non-FOBT group. Discussion: Decision-making and cognitive flexibility differences between gamblers grouped by gambling type supports preferred form as an important source of heterogeneity in gambling disorder. Decision-making strategies and risk attitudes should be considered when approaching cognition-focused treatment strategies, allowing interventions to be targeted at specific cognitive deficits

    Melatonin Alters Age-Related Changes in Transcription Factors and Kinase Activation

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    Male mice were fed 40 ppm melatonin for 2 months prior to sacrifice at age 26 months, and compared with both 26 and 4 month-old untreated controls. The nuclear translocation of NF-κB increased with age in both brain and spleen and this was reversed by melatonin only in brain. Another transcription factor, AP-1 was increased with age in the spleen and not in brain and this could be blocked by melatonin treatment. The fraction of the active relative to the inactive form of several enabling kinases was compared. The proportion of activated ERK was elevated with age in brain and spleen but this change was unresponsive to melatonin. A similar age-related increase in glial fibrillary acidic protein (GFAP) was also refractory to melatonin treatment. The cerebral melatonin M1 receptor decreased with age in brain but increased in spleen. The potentially beneficial nature of melatonin for the preservation of brain function with aging was suggested by the finding that an age-related decline in cortical synaptophysin levels was prevented by dietary melatonin

    Pore structural characterization of fuel cell layers using integrated mercury porosimetry and computerized X-ray tomography

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    The pore structure of the cathode catalyst layer of proton-exchange membrane (PEM) fuel cells is a major factor influencing cell performance. The nanostructure of the catalyst layer has been probed using a novel combination of mercury porosimetry with computerized X-ray tomography (CXT), even though the nanopores were below the nominal CXT resolution. The method allows probing of the macroscopic spatial variability in the accessibility of the nanostructure. In particular, mercury entrapment within the catalyst layer showed a pronounced regular spatial patterning corresponding to the already higher X-ray absorbing regions of the fresh catalyst layer. The initial, greater X-ray absorption was due to a higher local concentration of carbon-supported platinum catalyst. This was due to segregation of ionomer away from these areas caused by the particular screen printing catalyst layer deposition method used, which both enhanced the accessibility of the origin regions and, concomitantly, reduced the accessibility of the destination regions

    Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

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    BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010

    IUPHAR-DB: An Open-Access, Expert-Curated Resource for Receptor and Ion Channel Research

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    [Image: see text] This contribution highlights efforts by the International Union of Basic and Clinical Pharmacology (IUPHAR) Nomenclature Committee (NC-IUPHAR) to classify human receptors and ion channels, to document their properties, and to recommend ligands that are useful for characterization. This effort has inspired the creation of an online database (IUPHAR-DB), which is intended to provide free information to all scientists, summarized from primary literature by experts

    Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.

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    The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice

    Experimental Validation of a Forward Looking Interferometer for Detection of Clear Air Turbulence due to Mountain Waves

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    The Forward-Looking Interferometer (FLI) is an airborne sensor concept for detection and estimation of potential atmospheric hazards to aircraft. The FLI concept is based on high-resolution Infrared Fourier Transform Spectrometry technologies that have been developed for satellite remote sensing. The FLI is being evaluated for its potential to address multiple hazards, during all phases of flight, including clear air turbulence, volcanic ash, wake vortices, low slant range visibility, dry wind shear, and icing. In addition, the FLI is being evaluated for its potential to detect hazardous runway conditions during landing, such as wet or icy asphalt or concrete. The validation of model-based instrument and hazard simulation results is accomplished by comparing predicted performance against empirical data. In the mountain lee wave data collected in the previous FLI project, the data showed a damped, periodic mountain wave structure. The wave data itself will be of use in forecast and nowcast turbulence products such as the Graphical Turbulence Guidance and Graphical Turbulence Guidance Nowcast products. Determining how turbulence hazard estimates can be derived from FLI measurements will require further investigation

    Dynamic knowledge integration in socio-technical networks: an interpretive study of intranet use for knowledge integration

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    A major challenge facing firms competing in electronic business markets is the dynamic integration of knowledge within and beyond the firm, enabled by internet-based infrastructure and emergent fluid socio-technical networks. This paper explores how social actors dynamically employ intranets to integrate formal and informal knowledge within evolving socio-technical networks that emerge, permeate and extend beyond the organisational boundary. The paper presents two case studies that illustrate how static intranets can be useful for dynamically integrating knowledge when they are interwoven with other knowledge channels such as e-mail through which flows the informal knowledge needed to make sense of and situate formal organisational knowledge. The findings suggest that businesses should carefully examine how employees integrate intranets with other channels in their work, and the shaping of knowledge outcomes that flows from such use. There are practical implications for the proper skilling of thepeople who share and integrate knowledge in this way. The paper also provides a framework for dynamic knowledge integration in socio-technical networks, which can help underpin future research in this area.<br /
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