Addition of PTK787/ZK 222584 can lower the dosage of amsacrine to achieve equal amounts of acute myeloid leukemia cell death

Acute myeloid leukemia (AML) is a disease with a poor prognosis. It has been demonstrated that AML cells express the vascular endothelial growth factors, VEGFA and VEGFC, as well as kinase insert domain-containing receptor (VEGFR2), the main receptor for downstream effects, resulting in an autocrine pathway for cell survival. This study investigates the role of the VEGFR inhibitor PTK787/ZK 222584 in leukemic cell death, and the possibility of an additional effect on cell death by a chemotherapeutic drug, amsacrine. In three AML cell lines and 33 pediatric AML patient samples, we performed total cell-kill assays to determine the percentages of cell death achieved by PTK787/ZK 222584 and/or amsacrine. Both drugs induced AML cell death. Using a response surface analysis, we could show that, in cell lines as well as in primary AML blasts, an equal magnitude of leukemic cell death could be obtained when lower doses of the more toxic amsacrine were combined with low dosages of the less toxic VEGFR inhibitor. This study shows that PTK787/ ZK 222584 might have more clinical potential in AML when combined with a chemotherapeutic drug such as amsacrine. In future, it will be interesting to study whether the complications and the long-term effects of chemotherapy can be reduced by lowering the dosages of amsacrine, and by replacing it with other drugs with lower toxicity profiles, such as PTK787/ZK 222584

Dimensions of hospital nurse fatigue: Improving clinical outcomes with translational research

Session presented on Monday, July 27, 2015: Purpose: The purpose of this study was to evaluate a strategy to profile fatigue dimensions for hospital nurses. The American Nurses Association (2014) updated a position statement to address nurse fatigue to promote safety and health in September 2014. The statement emphasizes the joint or shared roles and responsibilities of registered nurse and their employers to reduce risks from nurse fatigue. A presidential task force from the American College of Occupational and Environmental Medicine (2012) on fatigue risk management recognized the significant impact of fatigue for employees in the 24/7 work environments. Many fatigue instruments have been used to test nurse fatigue, each measuring unique concepts and dimensions of fatigue. This research proposes to advance the investigation of hospital nurse fatigue using the framework of a hospital nurse fatigue theory (Drake, Luna, Georges & Barker-Steege, 2012) and evaluate fatigue dimensions sensitive to hospital nurses. The health, safety, and productivity of hospital nurses are at significant risk and can benefit from methods that clarify fatigue risk profiles and design targeted interventions. Methods: A secondary analysis of a hospital nurse fatigue survey was conducted using a cohort of patient-care (not manager or director) nurses. The initial study received Institutional Review Board approval and was a 100-item online survey. The hospital nurse fatigue survey was emailed to approximately 1000 hospital nurses. Of the 420 responders, 340 nurses completed 90% the survey items and 245 identified as patient-care nurse cohort. Latent profile analysis (LPA) was used to identify fatigue profiles for the patient-care nurse cohort based on five instruments that measure different concepts of fatigue: the Chalder Physical Fatigue Scale, Chalder Mental Fatigue Scale, Occupational Fatigue Exhaustion Recovery (OFER) Chronic Fatigue scale, OFER Acute Fatigue scale, and OFER Intershift Recovery scale. The investigators used the Mplus version 7.1 to conduct LPA and a range of information criteria such as AIC (Akaike\u27s information criterion), BIC (Bayesian information criterion), and CAIC (consistent AIC) to determine the best fit for the number of model profiles. Competing models (k profiles vs. k-1 profiles) were also evaluated using the Lo-Mendell-Rubin likelihood ratio test and the Vuong-Lo-Mendell-Rubin likelihood ratio test. ANOVA was performed comparing fatigue with professional, adaptive and bio-political variables to characterize differences between the profile groups. Results: A model with three latent profiles emerged as the best fit. The three profiles were categorized as: high fatigue/low recovery (23% of sample), moderate fatigue and recovery (30%), and low fatigue/high recovery (47%). Nurses in the high/fatigue low recovery group were significantly less likely to participate in meditation or exercise, have lower levels of job satisfaction and rate their hospital safety practice scores lower. Low fatigue/high recovery nurses were more likely to have less sleepiness, be older, worked as a nurse more years and rated their professional competency higher. Conclusion: The model with three latent profiles was a significant improvement upon a two-profile model. It is possible that more experienced hospital nurses may underrate their levels of fatigue, however it is likely they have developed strategies to improve recovery and have lower rates of fatigue. Strategies to improve work recovery and lower fatigue can be re-evaluated with informed awareness by nurses and employers. Hospital nurse fatigue is multidimensional and can be grouped into risk profiles to inform nurse fatigue policy, provide and test relevant interventions and promote improvements in related clinical outcomes

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

The Neonatal Development of Intraepithelial and Lamina Propria Lymphocytes in the Murine Small Intestine

During early neonatal life, important changes occur in the gut. The intestine is challenged by both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to pelleted food leading to changes in microbial contents. This period seems essential for a complete development of the mucosal immune system. We investigated the development of both intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3, TCRαβ, TCRγδ, CD4, CD8α, CD8β, CD5, CD18, CD54, and CD49d. Our data show a clear increase in the number of LPL just before weaning, while the number of IEL increased after day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular communication of lymphocytes, showed an expression peak at weaning. In conclusion, the mouse mucosal immune system develops during the first 3 weeks of neonatal life leading to the formation of a more mature immune system at weaning

Does the disturbance hypothesis explain the biomass increase in basin-wide Amazon forest plot data?

Positive aboveground biomass trends have been reported from old-growth forests across the Amazon basin and hypothesized to reflect a large-scale response to exterior forcing. The result could, however, be an artefact due to a sampling bias induced by the nature of forest growth dynamics. Here, we characterize statistically the disturbance process in Amazon old-growth forests as recorded in 135 forest plots of the RAINFOR network up to 2006, and other independent research programmes, and explore the consequences of sampling artefacts using a data-based stochastic simulator. Over the observed range of annual aboveground biomass losses, standard statistical tests show that the distribution of biomass losses through mortality follow an exponential or near-identical Weibull probability distribution and not a power law as assumed by others. The simulator was parameterized using both an exponential disturbance probability distribution as well as a mixed exponential–power law distribution to account for potential large-scale blowdown events. In both cases, sampling biases turn out to be too small to explain the gains detected by the extended RAINFOR plot network. This result lends further support to the notion that currently observed biomass gains for intact forests across the Amazon are actually occurring over large scales at the current time, presumably as a response to climate change

Amazon Basin forest pyrogenic carbon stocks: First estimate of deep storage

Amazon Basin forest soils contain considerable soil organic carbon stocks; however, the contribution of soil pyrogenic carbon (PyC) to the total is unknown. PyC is derived from local fires (historical and modern) and external inputs via aeolian deposition. To establish an initial estimate of PyC stocks in non-terra preta forest with no known history of fire, to assess site and vertical variability, as well as to determine optimal sampling design, we sampled 37 one hectare forest plots in the Amazon Basin and analysed PyC via hydrogen pyrolysis of three individual samples per plot and of bulked samples to 200 cm depth. Using our data and published total organic carbon stocks, we present the first field-based estimate of total PyC stock for the Amazon Basin of 1.10 Pg over 0–30 cm soil depth, and 2.76 Pg over 0–100 cm soil depth. This is up to 20 times higher than previously assumed. Three individual samples per 1 ha are sufficient to capture the site variability of PyC in our plots. PyC showed significant, large-scale variability among plots. To capture 50% of the PyC in 200 cm soil profiles, soil must be sampled to a depth of at least 71 cm. PyC represents a significant (11%) portion of total organic carbon in soil profiles 0–200 cm depth. This finding highlights the potentially important role that historical fire has played in modifying soil C stocks. Our data suggest that PyC is an important carbon pool for long-term storage, involved in millennial scale biogeochemical cycling, particularly in the subsurface soil

Phylogenetic diversity of Amazonian tree communities

This is the peer reviewed version of the following article: Honorio Coronado, E. N., Dexter, K. G., Pennington, R. T., Chave, J., Lewis, S. L., Alexiades, M. N., Alvarez, E., Alves de Oliveira, A., Amaral, I. L., Araujo-Murakami, A., Arets, E. J. M. M., Aymard, G. A., Baraloto, C., Bonal, D., Brienen, R., Cerón, C., Cornejo Valverde, F., Di Fiore, A., Farfan-Rios, W., Feldpausch, T. R., Higuchi, N., Huamantupa-Chuquimaco, I., Laurance, S. G., Laurance, W. F., López-Gonzalez, G., Marimon, B. S., Marimon-Junior, B. H., Monteagudo Mendoza, A., Neill, D., Palacios Cuenca, W., Peñuela Mora, M. C., Pitman, N. C. A., Prieto, A., Quesada, C. A., Ramirez Angulo, H., Rudas, A., Ruschel, A. R., Salinas Revilla, N., Salomão, R. P., Segalin de Andrade, A., Silman, M. R., Spironello, W., ter Steege, H., Terborgh, J., Toledo, M., Valenzuela Gamarra, L., Vieira, I. C. G., Vilanova Torre, E., Vos, V., Phillips, O. L. (2015), Phylogenetic diversity of Amazonian tree communities. Diversity and Distributions, 21: 1295–1307. doi: 10.1111/ddi.12357, which has been published in final form at 10.1111/ddi.12357Aim: To examine variation in the phylogenetic diversity (PD) of tree communities across geographical and environmental gradients in Amazonia. Location: Two hundred and eighty-three c. 1 ha forest inventory plots from across Amazonia. Methods: We evaluated PD as the total phylogenetic branch length across species in each plot (PDss), the mean pairwise phylogenetic distance between species (MPD), the mean nearest taxon distance (MNTD) and their equivalents standardized for species richness (ses.PDss, ses.MPD, ses.MNTD). We compared PD of tree communities growing (1) on substrates of varying geological age; and (2) in environments with varying ecophysiological barriers to growth and survival. Results: PDss is strongly positively correlated with species richness (SR), whereas MNTD has a negative correlation. Communities on geologically young- and intermediate-aged substrates (western and central Amazonia respectively) have the highest SR, and therefore the highest PDss and the lowest MNTD. We find that the youngest and oldest substrates (the latter on the Brazilian and Guiana Shields) have the highest ses.PDss and ses.MNTD. MPD and ses.MPD are strongly correlated with how evenly taxa are distributed among the three principal angiosperm clades and are both highest in western Amazonia. Meanwhile, seasonally dry tropical forest (SDTF) and forests on white sands have low PD, as evaluated by any metric. Main conclusions: High ses.PDss and ses.MNTD reflect greater lineage diversity in communities. We suggest that high ses.PDss and ses.MNTD in western Amazonia results from its favourable, easy-to-colonize environment, whereas high values in the Brazilian and Guianan Shields may be due to accumulation of lineages over a longer period of time. White-sand forests and SDTF are dominated by close relatives from fewer lineages, perhaps reflecting ecophysiological barriers that are difficult to surmount evolutionarily. Because MPD and ses.MPD do not reflect lineage diversity per se, we suggest that PDss, ses.PDss and ses.MNTD may be the most useful diversity metrics for setting large-scale conservation priorities.FINCyT - PhD studentshipSchool of Geography of the University of LeedsRoyal Botanic Garden EdinburghNatural Environment Research Council (NERC)Gordon and Betty Moore FoundationEuropean Union's Seventh Framework ProgrammeERCCNPq/PELDNSF - Fellowshi