898 research outputs found

    The Effectiveness of High Dose Chemotherapy and Bone Marrow/Autologous Stem Cell Transplantation in the Treatment of Multiple Myeloma

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    The Co-Production of Sustainable Future Scenarios

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    Scenarios are a tool to develop plausible, coherent visions about the future and to foster anticipatory knowledge. We present the Sustainable Future Scenarios (SFS) framework and demonstrate its application through the Central Arizona-Phoenix Long-term Ecological Research (CAP LTER) urban site. The SFS approach emphasizes the co-development of positive and long-term alternative future visions. Through a collaboration of practitioner and academic stakeholders, this research integrates participatory scenario development, modeling, and qualitative scenario assessments. The SFS engagement process creates space to question the limits of what is normally considered possible, desirable, or inevitable in the face of future challenges. Comparative analyses among the future scenarios demonstrate trade-offs among regional and microscale temperature, water use, land-use change, and co-developed resilience and sustainability indices. SFS incorporate diverse perspectives in co-producing positive future visions, thereby expanding traditional future projections. The iterative, interactive process also creates opportunities to bridge science and policy by building anticipatory and systems-based decision-making and research capacity for long-term sustainability planning

    FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

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    Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)

    Study Protocol: The Behaviour and Pain in Dementia Study (BePAID)

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    <p>Abstract</p> <p>Background</p> <p>People with dementia admitted to the acute hospital often receive poor quality care particularly with regards to management of behavioural and psychiatric symptoms of dementia (BPSD) and of pain. There have been no UK studies on the prevalence and type of pain or BPSD in people with dementia in this setting, or on how these may impact on patients, carers, staff and costs of care.</p> <p>Methods/Design</p> <p>We shall recruit older people with dementia who have unplanned acute medical admissions and measure the prevalence of BPSD using the Behave-AD (Behaviour in Alzheimer's Disease) and the CMAI (Cohen Mansfield Agitation Inventory). Pain prevalence and severity will be assessed by the PAINAD (Pain Assessment in Advanced Dementia) and the FACES pain scale. We will then analyse how these impact on a variety of outcomes and test the hypothesis that poor management of pain is associated with worsening of BPSD.</p> <p>Discussion</p> <p>By demonstrating the costs of BPSD to individuals with dementia and the health service this study will provide important evidence to drive improvements in care. We can then develop effective training for acute hospital staff and alternative treatment strategies for BPSD in this setting.</p

    Mitigating oxygen stress enhances aged mouse hematopoietic stem cell numbers and function

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    Bone marrow (BM) hematopoietic stem cells (HSCs) become dysfunctional during aging (i.e., they are increased in number but have an overall reduction in long-term repopulation potential and increased myeloid differentiation) compared with young HSCs, suggesting limited use of old donor BM cells for hematopoietic cell transplantation (HCT). BM cells reside in an in vivo hypoxic environment yet are evaluated after collection and processing in ambient air. We detected an increase in the number of both young and aged mouse BM HSCs collected and processed in 3% O2 compared with the number of young BM HSCs collected and processed in ambient air (~21% O2). Aged BM collected and processed under hypoxic conditions demonstrated enhanced engraftment capability during competitive transplantation analysis and contained more functional HSCs as determined by limiting dilution analysis. Importantly, the myeloid-to-lymphoid differentiation ratio of aged BM collected in 3% O2 was similar to that detected in young BM collected in ambient air or hypoxic conditions, consistent with the increased number of common lymphoid progenitors following collection under hypoxia. Enhanced functional activity and differentiation of old BM collected and processed in hypoxia correlated with reduced “stress” associated with ambient air BM collection and suggests that aged BM may be better and more efficiently used for HCT if collected and processed under hypoxia so that it is never exposed to ambient air O2

    Search for Anisotropy of Ultra-High Energy Cosmic Rays with the Telescope Array Experiment

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    We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.Comment: 10 pages, 9 figure

    First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

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    Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

    Psychotic Experiences in the General Population: A Cross-National Analysis Based on 31,261 Respondents From 18 Countries

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    IMPORTANCE: Community-based surveys find that many otherwise healthy individuals report histories of hallucinations and delusions. To date, most studies have focused on the overall lifetime prevalence of any of these psychotic experiences (PEs), which might mask important features related to the types and frequencies of PEs. OBJECTIVE: To explore detailed epidemiologic information about PEs in a large multinational sample. DESIGN, SETTING, AND PARTICIPANTS: We obtained data from the World Health Organization World Mental Health Surveys, a coordinated set of community epidemiologic surveys of the prevalence and correlates of mental disorders in representative household samples from 18 countries throughout the world, from 2001 through 2009. Respondents included 31,261 adults (18 years and older) who were asked about lifetime and 12-month prevalence and frequency of 6 types of PEs (2 hallucinatory experiences and 4 delusional experiences). We analyzed the data from March 2014 through January 2015. MAIN OUTCOMES AND MEASURES: Prevalence, frequency, and correlates of PEs. RESULTS: Mean lifetime prevalence (SE) of ever having a PE was 5.8% (0.2%), with hallucinatory experiences (5.2% [0.2%]) much more common than delusional experiences (1.3% [0.1%]). More than two-thirds (72.0%) of respondents with lifetime PEs reported experiencing only 1 type. Psychotic experiences were typically infrequent, with 32.2% of respondents with lifetime PEs reporting only 1 occurrence and 31.8% reporting only 2 to 5 occurrences. We found a significant relationship between having more than 1 type of PE and having more frequent PE episodes (Cochran-Armitage z = -10.0; P < .001). Lifetime prevalence estimates (SEs) were significantly higher among respondents in middle- and high-income countries than among those in low-income countries (7.2% [0.4%], 6.8% [0.3%], and 3.2% [0.3%], respectively; χ²₂ range, 7.1-58.2; P < .001 for each) and among women than among men (6.6% [0.2%] vs 5.0% [0.3%]; χ²₁ = 16.0; P < .001). We found significant associations with lifetime prevalence of PEs in the multivariate model among nonmarried compared with married respondents (χ²₂ = 23.2; P < .001) and among respondents who were not employed (χ²₄= 10.6; P < .001) and who had low family incomes (χ²₃ = 16.9; P < .001). CONCLUSIONS AND RELEVANCE: The epidemiologic features of PEs are more nuanced than previously thought. Research is needed that focuses on similarities and differences in the predictors of the onset, course, and consequences of distinct PEs
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