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

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

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

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

No abstract available

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

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

HLA-DR genotyping and mitochondrial DNA analysis reveal the presence of family burials in a fourth century Romano-British Christian cemetery

In Colchester, Britain's oldest recorded town, during the Roman period there were areas which were clearly used solely as cemeteries. One o f the most significant is at Butt Road, which includes a late Roman probable Christian cemetery with an associated building, apparently a church, that overlies and developed from a pagan inhumation cemetery. DNA was extracted from the long bones (femurs) of 29 individuals, mostly from a large complex of burials centered on two timber vaults. These were thought to comprise a number of family groupings, deduced from osteological analysis, stratigraphical and other considerations. The use of a modified version of the silica-based purification method recovered nanogram quantities of DNA/gram of bone. Two-stage amplification, incorporating primer-extension preamplification-polymerase chain reaction, permitted simultaneous amplification of both mitochondrial and nuclear DNA. Sequence-specific oligonucleotide probes yielded human leukocyte antigen (HLA)-DR typing of seven samples, with four revealing the infrequent HLA-DR10 genotype. Examination of the control region of mitochondrial DNA (mtDNA) by direct sequencing revealed polymorphisms yet to be reported in the modern population. HLA-DRB typing and mtDNA analysis affirmatively supported kinship among some, if not all, individuals in the "vault complex" and demonstrate a continental European origin of the individuals investigated

Ecology: a prerequisite for malaria elimination and eradication

* Existing front-line vector control measures, such as insecticide-treated nets and residual sprays, cannot break the transmission cycle of Plasmodium falciparum in the most intensely endemic parts of Africa and the Pacific * The goal of malaria eradication will require urgent strategic investment into understanding the ecology and evolution of the mosquito vectors that transmit malaria * Priority areas will include understanding aspects of the mosquito life cycle beyond the blood feeding processes which directly mediate malaria transmission * Global commitment to malaria eradication necessitates a corresponding long-term commitment to vector ecolog

Multimorbidity in bipolar disorder and under-treatment of cardiovascular disease: a cross sectional study

Background: Individuals with serious mental disorders experience poor physical health, especially increased rates of cardiometabolic morbidity and premature morbidity. Recent evidence suggests that individuals with schizophrenia have numerous comorbid physical conditions which may be under-recorded and under-treated but to date very few studies have explored this issue for bipolar disorder. Methods:We conducted a cross-sectional analysis of a dataset of 1,751,841 registered patients within 314 primary-care practices in Scotland, U.K. Bipolar disorder was identified using Read Codes recorded within electronic medical records. Data on 32 common chronic physical conditions were also assessed. Potential prescribing inequalities were evaluated by analyzing prescribing data for coronary heart disease (CHD) and hypertension. Results: Compared to controls, individuals with bipolar disorder were significantly less likely to have no recorded physical conditions (OR 0.59, 95% CI 0.54-0.63) and significantly more likely to have one physical condition (OR 1.27, 95% CI 1.16-1.39), two physical conditions (OR 1.45, 95% CI 1.30-1.62) and three or more physical conditions (OR 1.44, 95% CI 1.30-1.64). People with bipolar disorder also had higher rates of thyroid disorders, chronic kidney disease, chronic pain, chronic obstructive airways disease and diabetes but, surprisingly, lower recorded rates of hypertension and atrial fibrillation. People with bipolar disorder and comorbid CHD or hypertension were significantly more likely to be prescribed no antihypertensive or cholesterol-lowering medications compared to controls, and bipolar individuals with CHD or hypertension were significantly less likely to be on 2 or more antihypertensive agents. Conclusions: Individuals with bipolar disorder are similar to individuals with schizophrenia in having a wide range of comorbid and multiple physical health conditions. They are also less likely than controls to have a primary-care record of cardiovascular conditions such as hypertension and atrial fibrillation. Those with a recorded diagnosis of CHD or hypertension were less likely to be treated with cardiovascular medications and were treated less intensively. This study highlights the high physical healthcare needs of people with bipolar disorder, and provides evidence for a systematic under-recognition and under-treatment of cardiovascular disease in this group