Biomarkers of leukemia risk: benzene as a model.

Although relatively rare, leukemias place a considerable financial burden on society and cause psychologic trauma to many families. Leukemia is the most common cancer in children. The causes of leukemia in adults and children are largely unknown, but occupational and environmental factors are strongly suspected. Genetic predisposition may also play a major role. Our aim is to use molecular epidemiology and toxicology to find the cause of leukemia and develop biomarkers of leukemia risk. We have studied benzene as a model chemical leukemogen, and we have identified risk factors for susceptibility to benzene toxicity. Numerous studies have associated exposure to benzene with increased levels of chromosome aberrations in circulating lymphocytes of exposed workers. Increased levels of chromosome aberrations have, in turn, been correlated with a heightened risk of cancer, especially for hematologic malignancy, in two recent cohort studies in Europe. Conventional chromosome analysis is laborious, however, and requires highly trained personnel. Further, it lacks statistical power, as only a small number of cells can be examined. The recently developed fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR)-based technologies have allowed the detection of specific chromosome aberrations. These techniques are far less time consuming and are more sensitive than classical chromosomal analysis. Because leukemias commonly show a variety of specific chromosome aberrations, detection of these aberrations by FISH and PCR in peripheral blood may provide improved biomarkers of leukemia risk

Drawing Boundaries

In “On Drawing Lines on a Map” (1995), I suggested that the different ways we have of drawing lines on maps open up a new perspective on ontology, resting on a distinction between two sorts of boundaries: fiat and bona fide. “Fiat” means, roughly: human-demarcation-induced. “Bona fide” means, again roughly: a boundary constituted by some real physical discontinuity. I presented a general typology of boundaries based on this opposition and showed how it generates a corresponding typology of the different sorts of objects which boundaries determine or demarcate. In this paper, I describe how the theory of fiat boundaries has evolved since 1995, how it has been applied in areas such as property law and political geography, and how it is being used in contemporary work in formal and applied ontology, especially within the framework of Basic Formal Ontology

The changing nature of risk and risk management: the challenge of borders, uncertainty and resilience

No abstract available

Heat stress incident prevalence and tennis matchplay performance at the Australian Open

© 2017 Sports Medicine Australia Objectives: To examine the association of wet bulb globe temperature (WBGT) with the occurrence of heat-related incidents and changes in behavioural and matchplay characteristics in men's Grand Slam tennis. Design: On-court calls for trainers, doctors, cooling devices and water, post-match medical consults and matchplay characteristic data were collected from 360 Australian Open matches (first 4 rounds 2014–2016). Methods: Data were referenced against estimated WBGT and categorised into standard zones. Generalised linear models assessed the association of WBGT zone on heat-related medical incidences and matchplay variables. Results: On-court calls for doctor (47% increase per zone, p = 0.001), heat-related events (41%, p = 0.019), cooling devices (53%, p 32 °C and >28 °C, significant increases in heat-related calls (p = 0.019) and calls for cooling devices (p 32 °C) and cooling device callouts (>28 °C). However, few matchplay characteristics were noticeably affected, with only reduced net approaches and increased aces evident in higher estimated WBGT environments

Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel

Will more of the same achieve malaria elimination? Results from an integrated macroeconomic epidemiological demographic model

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThe data underlying the model framework are available from the authors on request and selected parameters are also tabulated in the methods paper,22 and from the Malaria Atlas Project http:// www.map.ox.ac.uk/Historic levels of funding have reduced the global burden of malaria in recent years. Questions remain, however, as to whether scaling up interventions, in parallel with economic growth, has made malaria elimination more likely today than previously. The consequences of “trying but failing” to eliminate malaria are also uncertain. Reduced malaria exposure decreases the acquisition of semi-immunity during childhood, a necessary phase of the immunological transition that occurs on the pathway to malaria elimination. During this transitional period, the risk of malaria resurgence increases as proportionately more individuals across all age-groups are less able to manage infections by immune response alone. We developed a robust model that integrates the effects of malaria transmission, demography, and macroeconomics in the context of Plasmodium falciparum malaria within a hyperendemic environment. We analyzed the potential for existing interventions, alongside economic development, to achieve malaria elimination. Simulation results indicate that a 2% increase in future economic growth will increase the US$5.1 billion cumulative economic burden of malaria in Ghana to US$7.2 billion, although increasing regional insecticide-treated net coverage rates by 25% will lower malaria reproduction numbers by just 9%, reduce population-wide morbidity by −0.1%, and reduce prevalence from 54% to 46% by 2034. As scaling up current malaria control tools, combined with economic growth, will be insufficient to interrupt malaria transmission in Ghana, high levels of malaria control should be maintained and investment in research and development should be increased to maintain the gains of the past decade and to minimize the risk of resurgence, as transmission dropsMedical Research Council (MRC

Linking forest cover, soil erosion and mire hydrology to late-Holocene human activity and climate in NW Spain

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (http://www.uk.sagepub.com/aboutus/openaccess.htm).This article has been made available through the Brunel Open Access Publishing Fund.Forest clearance is one of the main drivers of soil erosion and hydrological changes in mires, although climate may also play a significant role. Because of the wide range of factors involved, understanding these complex links requires long-term multi-proxy approaches and research on the best proxies to focus. A peat core from NW Spain (Cruz do Bocelo mire), spanning the last ~3000 years, has been studied at high resolution by physical (density and loss on ignition (LOI)), geochemical (elemental composition) and palynological (pollen and non-pollen palynomorphs) analyses. Proxies related to mineral matter fluxes from the catchment (lithogenic tracers, Glomus and Entorrhiza), rainfall (Bromine), mire hydrology (HdV-18), human pressure (Cerealia-type, nitrophilous taxa and coprophilous fungi) and forest cover (mesophilous tree taxa) were the most useful to reconstruct the evolution of the mire and its catchment. Forest clearance for farming was one of the main drivers of environmental change from at least the local Iron Age (~2685 cal. yr BP) onwards. The most intense phase of deforestation occurred during Roman and Germanic times and the late Middle Ages. During these phases, the entire catchment was affected, resulting in enhanced soil erosion and severe hydrological modifications of the mire. Climate, especially rainfall, may have also accelerated these processes during wetter periods. However, it is noteworthy that the hydrology of the mire seems to have been insensitive to rainfall variations when mesophilous forest dominated. Abrupt changes were only detected once intense forest clearance commenced during the Iron Age/Roman transition (~2190 cal. yr BP) phase, which represented a tipping point in catchment's ability to buffer impacts. Overall, our findings highlight the importance of studying ecosystems' long-term trajectories and catchment-wide processes when implementing mire habitat protection measures.This work was funded by the projects CGL2010-20672 (Plan Nacional I+D+i, Spanish Ministry of Science and Innovation) and 10PXIB200182PR (General Directorate of I+D, Xunta de Galicia). N Silva-Sánchez and L López-Merino are currently supported by a FPU predoctoral scholarship (AP2010-3264) funded by the Spanish Government and a MINT postdoctoral fellowship funded by the Brunel Institute for the Environment, respectively

GP-SUM. Gaussian Processes Filtering of non-Gaussian Beliefs

This work studies the problem of stochastic dynamic filtering and state propagation with complex beliefs. The main contribution is GP-SUM, a filtering algorithm tailored to dynamic systems and observation models expressed as Gaussian Processes (GP), and to states represented as a weighted sum of Gaussians. The key attribute of GP-SUM is that it does not rely on linearizations of the dynamic or observation models, or on unimodal Gaussian approximations of the belief, hence enables tracking complex state distributions. The algorithm can be seen as a combination of a sampling-based filter with a probabilistic Bayes filter. On the one hand, GP-SUM operates by sampling the state distribution and propagating each sample through the dynamic system and observation models. On the other hand, it achieves effective sampling and accurate probabilistic propagation by relying on the GP form of the system, and the sum-of-Gaussian form of the belief. We show that GP-SUM outperforms several GP-Bayes and Particle Filters on a standard benchmark. We also demonstrate its use in a pushing task, predicting with experimental accuracy the naturally occurring non-Gaussian distributions.Comment: WAFR 2018, 16 pages, 7 figure

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans

Outcomes following autologous hematopoietic stem cell transplant for patients with relapsed Wilms' tumor: a CIBMTR retrospective analysis.

Despite the marked improvement in the overall survival (OS) for patients diagnosed with Wilms' tumor (WT), the outcomes for those who experience relapse have remained disappointing. We describe the outcomes of 253 patients with relapsed WT who received high-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplant (HCT) between 1990 and 2013, and were reported to the Center for International Blood and Marrow Transplantation Research. The 5-year estimates for event-free survival (EFS) and OS were 36% (95% confidence interval (CI); 29-43%) and 45% (95 CI; 38-51%), respectively. Relapse of primary disease was the cause of death in 81% of the population. EFS, OS, relapse and transplant-related mortality showed no significant differences when broken down by disease status at transplant, time from diagnosis to transplant, year of transplant or conditioning regimen. Our data suggest that HDT followed by autologous HCT for relapsed WT is well tolerated and outcomes are similar to those reported in the literature. As attempts to conduct a randomized trial comparing maintenance chemotherapy with consolidation versus HDT followed by stem cell transplant have failed, one should balance the potential benefits with the yet unknown long-term risks. As disease recurrence continues to be the most common cause of death, future research should focus on the development of consolidation therapies for those patients achieving complete response to therapy