Elevated white blood cell levels and thrombotic events in patients with polycythemia vera: a real-world analysis of veterans health administration data

Background: Patients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). The objective of the present analysis was to describe the association between white blood cell (WBC) levels and occurrence of TEs among patients with PV from a large real-world population. Patients and Methods: The present retrospective analysis using Veterans Health Administration claims data (October 1, 2005, to September 30, 2012) evaluated adult patients assigned to 4 WBC count categories (WBC count < 7.0, 7.0-8.4, 8.5 to < 11.0, and ≥ 11.0 × 109/L) to compare the risk of TEs (reference, WBC count, < 7.0 × 109/L group). Analysis was performed using a Cox proportional hazards model, considering WBC status as a time-dependent covariate. Results: Of the 1565 patients with PV included in the present analysis, the WBC count was < 7.0 × 109/L for 428 (27.3%), 7.0 to 8.4 × 109/L for 375 (24.0%), 8.5 to < 11.0 × 109/L for 284 (18.1%), and ≥ 11.0 × 109/L for 478 (30.5%). Of the 1565 patients, 390 (24.9%) had experienced a TE during the study period. The mean follow-up ranged from 3.6 to 4.5 years. Compared with the reference group (WBC count < 7.0 ×109/L), the hazard ratio for TEs was 1.10 (95% confidence interval [CI], 0.82-1.48; P = .5395), 1.47 (95% CI, 1.10-1.96; P = .0097), and 1.87 (95% CI, 1.44-2.43; P < .0001) for patients with a WBC count of 7.0 to 8.4, 8.5 to < 11.0, and ≥ 11.0 ×109/L, respectively. Conclusion: A positive, significant association between an increased WBC count of ≥ 8.5 ×109/L and the occurrence of TEs was observed in patients with PV. The potential thrombogenic role of WBCs in patients with PV supports the continued inclusion of WBC count control in disease management and evaluation of the response to therapy. © 2019 The AuthorsPatients with polycythemia vera (PV) have a substantial risk of thrombotic events (TEs). In the present retrospective analysis using Veterans Health Administration claims data, 25% of 1565 patients experienced a TE during follow-up. We observed a positive, significant association between white blood cell (WBC) counts ≥ 8.5 × 109/L and TE occurrence (reference, WBC count < 7.0 × 109/L), supporting continued inclusion of WBC count control in disease management. © 2019 The AuthorsIncyte Corporation (Wilmington, DE)WOS:000513918800013Scopus - Affiliation ID: 60105072PMID: 31865003Science Citation Index ExpandedQ3ArticleUluslararası işbirliği ile yapılan - EVETŞubat2020YÖK - 2019-2

Maze solvers demystified and some other thoughts

There is a growing interest towards implementation of maze solving in spatially-extended physical, chemical and living systems. Several reports of prototypes attracted great publicity, e.g. maze solving with slime mould and epithelial cells, maze navigating droplets. We show that most prototypes utilise one of two phenomena: a shortest path in a maze is a path of the least resistance for fluid and current flow, and a shortest path is a path of the steepest gradient of chemoattractants. We discuss that substrates with so-called maze-solving capabilities simply trace flow currents or chemical diffusion gradients. We illustrate our thoughts with a model of flow and experiments with slime mould. The chapter ends with a discussion of experiments on maze solving with plant roots and leeches which show limitations of the chemical diffusion maze-solving approach.Comment: This is a preliminary version of the chapter to be published in Adamatzky A. (Ed.) Shortest path solvers. From software to wetware. Springer, 201

When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Multifunctional shade‐tree management in tropical agroforestry landscapes – a review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87099/1/j.1365-2664.2010.01939.x.pd

Grain Yield Stability of Cereal-Legume Intercrops Is Greater Than Sole Crops in More Productive Conditions

The intercropping of two or more crop species on the same piece of land at a given time has been hypothesized to enhance crop yield stability. To address this hypothesis, we assessed the grain yield stability of various barley-pea and wheat-faba bean mixtures grown in seven experimental field trials (locations) across Europe during two years with contrasting weather (2017 and 2018). Three different yield stability measures were used, all based on the expected yield variability of the mixture components grown as sole crops, and the corresponding observed yield variability of the same components grown in 50:50 mixtures in a replacement design. Stability indices were calculated as ratios between the expected and observed variabilities, with values > 1 indicating greater stability of the intercrops. Mean grain yields tended to be higher in intercrops than sole crops. However, in contrast to our hypothesis, the observed (intercrop) yield stability was similar or lower than the expected (sole crop) stability in most locations except one. Furthermore, yield stability significantly increased with increasing mean yields when assessed across differentially productive locations. The results are relevant for the designing of intercropping systems as a means to increase yield stability and the resilience of cropping systems.This research was funded by the DIVERSify project, a grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 727284. MR was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—420661662. A.J.K. and A.C.N. are also supported by the strategic research programme funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division.Peer reviewe

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Biodiversity Loss and the Taxonomic Bottleneck: Emerging Biodiversity Science

Human domination of the Earth has resulted in dramatic changes to global and local patterns of biodiversity. Biodiversity is critical to human sustainability because it drives the ecosystem services that provide the core of our life-support system. As we, the human species, are the primary factor leading to the decline in biodiversity, we need detailed information about the biodiversity and species composition of specific locations in order to understand how different species contribute to ecosystem services and how humans can sustainably conserve and manage biodiversity. Taxonomy and ecology, two fundamental sciences that generate the knowledge about biodiversity, are associated with a number of limitations that prevent them from providing the information needed to fully understand the relevance of biodiversity in its entirety for human sustainability: (1) biodiversity conservation strategies that tend to be overly focused on research and policy on a global scale with little impact on local biodiversity; (2) the small knowledge base of extant global biodiversity; (3) a lack of much-needed site-specific data on the species composition of communities in human-dominated landscapes, which hinders ecosystem management and biodiversity conservation; (4) biodiversity studies with a lack of taxonomic precision; (5) a lack of taxonomic expertise and trained taxonomists; (6) a taxonomic bottleneck in biodiversity inventory and assessment; and (7) neglect of taxonomic resources and a lack of taxonomic service infrastructure for biodiversity science. These limitations are directly related to contemporary trends in research, conservation strategies, environmental stewardship, environmental education, sustainable development, and local site-specific conservation. Today’s biological knowledge is built on the known global biodiversity, which represents barely 20% of what is currently extant (commonly accepted estimate of 10 million species) on planet Earth. Much remains unexplored and unknown, particularly in hotspots regions of Africa, South Eastern Asia, and South and Central America, including many developing or underdeveloped countries, where localized biodiversity is scarcely studied or described. ‘‘Backyard biodiversity’’, defined as local biodiversity near human habitation, refers to the natural resources and capital for ecosystem services at the grassroots level, which urgently needs to be explored, documented, and conserved as it is the backbone of sustainable economic development in these countries. Beginning with early identification and documentation of local flora and fauna, taxonomy has documented global biodiversity and natural history based on the collection of ‘‘backyard biodiversity’’ specimens worldwide. However, this branch of science suffered a continuous decline in the latter half of the twentieth century, and has now reached a point of potential demise. At present there are very few professional taxonomists and trained local parataxonomists worldwide, while the need for, and demands on, taxonomic services by conservation and resource management communities are rapidly increasing. Systematic collections, the material basis of biodiversity information, have been neglected and abandoned, particularly at institutions of higher learning. Considering the rapid increase in the human population and urbanization, human sustainability requires new conceptual and practical approaches to refocusing and energizing the study of the biodiversity that is the core of natural resources for sustainable development and biotic capital for sustaining our life-support system. In this paper we aim to document and extrapolate the essence of biodiversity, discuss the state and nature of taxonomic demise, the trends of recent biodiversity studies, and suggest reasonable approaches to a biodiversity science to facilitate the expansion of global biodiversity knowledge and to create useful data on backyard biodiversity worldwide towards human sustainability