A case-control study of mesothelioma in South Africa

This thesis reports the results of a prospective multicentred case-control study of mesothelioma carried out in South Africa. The objectives of the study were: 1) to examine asbestos exposure of cases in detail with respect to source, risk occupations, fibre type and duration; 2) to determine relative risks for level (certainty) of exposure (definite, probable, possible, unlikely), for category of exposure (occupational, environmental), and for fibre type and skin colour; 3) to determine whether cases without recall of exposure were exposed to other non-asbestos putative agents; 4) to investigate the possible protective effect of certain dietary components. Previous studies of mesothelioma in South Africa had, with the exception of one incidence study, focused on particular occupational or case material, exposure data had been gathered in a non-systematic way, often indirectly from surrogates, and non-asbestos agents had not been investigated. In this case-control study these issues are all addressed. In addition, special efforts were made to minimise potential sources of bias (e.g. interviewer bias) and so to furnish reliable effect estimates. The study incorporated the following methodological features: 1) a prospective approach to gather exposure and dietary information directly from the cases and controls in life and so avoid the use of surrogates for this information; 2) the study was multicentred with study teams established in six cities, each with a major referral hospital, to maximise nation-wide coverage; 3) information was gathered with interviewers blind (at least at the beginning of the study) to study objectives and case control status at the time of the interview; 4) rigorous pathologic review was used to establish the diagnosis of mesothelioma; 5) two controls were selected for each case, a cancer and a non-cancer patient matched for hospital, sex, age and skin colour; 6) in analysis the case control datasets were treated separately (i.e cases and cancer controls, and cases and non-cancer controls were treated as two separate datasets). One hundred and twenty three cases were accepted into the study. No case was documented with purely chrysotile exposure nor exposure to a putative non-asbestos cause of the tumour without some evidence of asbestos exposure. A minimum of 22 cases (18%) had exclusively environmental exposure, 20 were from the NW Cape (a crocidolite mining region). Fifty eight percent had occupational exposure, three of whom had mined amosite. The relative risks associated environmental exposure in the NW Cape were larger than for environmental exposure in the NE Transvaal: 21.9 versus 7.1 for the cancer control dataset and 50.9 versus 12.0 for the medical control dataset. Increasing consumption of carotene rich fruit was found to be protective for mesothelioma when adjusted for asbestos exposure. The results confirm the high disease burden due to occupational exposure, the importance of environmental exposure in the crocidolite mining area of the NW Cape, the relative paucity of cases linked to amosite, the rarity of chrysotile cases, and are consistent with the view that there is a fibre gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile. The evidence for a protective effect of carotene rich fruit is new in the South African context

Bandwidth enhancement : correcting magnitude and phase distortion in wideband piezoelectric transducer systems

Acoustic ultrasonic measurements are widespread and commonly use transducers exhibiting resonant behaviour due to the piezoelectric nature of their active elements, being designed to give maximum sensitivity in the bandwidth of interest. We present a characterisation of such transducers that provides both magnitude and phase information describing the way in which the receiver responds to a surface displacement over its frequency range. Consequently, these devices work efficiently and linearly over only a very narrow band of their overall frequency range. In turn, this causes phase and magnitude distortion of linear signals. To correct for this distortion, we introduce a software technique, which considers only the input and the final output signals of the whole systemwhich is therefore generally applicable to any acoustic system. By correcting for the distortion of the magnitude and phase responses, we have ensured the signal seen at the receiver replicates the desired signal. We demonstrate a bandwidth extension on the received signal from 60-130 kHz at -6dB to 40-200 kHz at -1dB in a test system. The linear chirp signal we used to demonstrate this method showed the received signal to be almost identical to the desired linear chirp. Such systemcharacterisation will improve ultrasonic techniques when investigating material properties by maximising the accuracy of magnitude and phase estimations

How benign is sickle cell trait?

This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.ebiom.2016.08.023

Lipid metabolism in terminal erythropoiesis.

In this issue of Blood, Huang et al have provided evidence that altered lipid metabolism is critical for terminal erythropoiesis. A key role is proposed for the PHOSPHO1 gene product, a phosphocholine phosphatase. PHOSPHO1 knockouts (KOs) showed reduced erythroblast proliferation and enucleation in both mice and human erythroid tissues, apparently through energy depletion mediated via inhibition of oxidative phosphorylation of fatty acids and reduced adenosine triphosphate (ATP) production in late glycolysis. This work emphasizes that altered expression of genes involving lipid metabolism are important during late red cell maturation

Role of Calcium in Phosphatidylserine Externalisation in Red Blood Cells from Sickle Cell Patients

Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca2+ entry, providing an obvious link with phosphatidylserine exposure. The role of Ca2+ was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca2+] was increased. This effect was inhibited by dipyridamole, intracellular Ca2+ chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K+ saline. Ca2+ levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca2+ entry through the deoxygenation-induced pathway (Psickle), activating the Gardos channel. [Ca2+] required for phosphatidylserine scrambling are in the range achievable in vivo

Oxidative stress and haemolytic anaemia in dogs and cats: a comparative approach

Oxidative stress contributes to haemolytic anaemia in many species including dogs and cats, as well as in humans. Red cells are exposed to a continual oxidant challenge, both endogenously from within the red cells themselves and also exogenously from other tissues, and from ingested or administered oxidants. When the oxidative challenge exceeds the antioxidant provisions of the red cell, damage occurs in the form of lipid and protein peroxidation, cytoskeletal crosslinking, oxidation of haemoglobin to methaemolglobin, and precipitation of denatured sulphhaemoglobin as Heinz bodies. These deleterious sequelae produce fragile red cells with reduced lifespan, and result in poorer oxygen delivery to tissues, intravascular haemolysis, anaemia, haemoglobinuria and jaundice. A number of features increase the risk of oxidant damage in dogs and cats. Thus dog red cells have low levels of the antioxidant enzyme catalase. Cat haemoglobin has at least four times as many readily oxidizable thiol residues compared to most species, whilst their hepatic capacity for glucuronidation is much reduced, which can result in greater accumulation of oxidants. Like humans, both species may also be exposed to excess oxidants from systemic diseases such as diabetes mellitus, hepatic lipidosis, hypophosphataemia and neoplasias. Iatrogenic oxidants include drugs such as acetaminophen and other non-steroidal anti-inflammatory compounds. Ingested toxins include heavy metals, particularly important in dogs with their increased propensity for scavenging. Ingestion of feeds containing products from Allium species of plants has also long been associated with red cell oxidative damage and Heinz body formation in both dogs and cats. Though less common than in humans, there are occasional congenital enzyme deficiencies which reduce the enzymatic oxidant defence of the red cells in these species. Treatment usually relies on removal of the oxidant challenge or support against the resulting anaemia. Specific antioxidants currently lack efficacy but analogy with human medicine suggests that a range possible antioxidants may be potentially beneficial.Non

Mineralogy and Malignant Mesothelioma: The South African Experience

South Africa is a uniquely mineral rich country. Of the six types of asbestiform minerals found in the country, three, namely crocidolite, amosite and chrysotile were mined and milled on a large commercial scale. Asbestos was used locally in South Africa, but the majority of its production was exported worldwide. In the 1970s, South Africa was the world’s third largest producer of asbestos, behind Canada and the USSR. About 97% of the world’s production of crocidolite and virtually all of the amosite came from South Africa. The output from the South African asbestos mining industry peaked at 380,000 tonnes in 1977 and declined thereafter as export markets declined due to restrictive legislation in countries that imported asbestos (Virta, 2006; Kielkowski et al., 2011). Legislation in South Africa banning the use of all types of asbestos came into effect in 2008, well after the last asbestos mine ceased production in 2001 and closed in 2002. Although South Africa benefitted financially from the exploitation of its asbestos mineral reserves, the revenue from asbestos never accounted for more than 3% of the value of its total minerals output (McCulloch, 2003). There is however a high price to pay in terms of a legacy of disease and environmental contamination through mining activities and the transport of asbestos and asbestos containing products

First recorded occurrence of the parasitic barnacle (Anelasma squalicola) on a Greenland shark (Somniosus microcephalus) in the Canadian Arctic

A solitary Anelasma squalicola specimen was collected from the cloaca of a Greenland shark (Somniosus microcephalus), the first time this association has been recorded. The specimen's identity was confirmed through morphological and genetic assessment (mitochondrial markers: COI and control region). A. squalicola is a species typically associated with deep-sea lantern sharks (Etmopteridae) and, until the present observation, had never been observed at a sexually mature size in the absence of a mating partner. Given the reported negative effects of this parasite on its hosts, monitoring Greenland sharks for additional cases is recommended.publishedVersio

GeneXplorer: an interactive web application for microarray data visualization and analysis

BACKGROUND: When publishing large-scale microarray datasets, it is of great value to create supplemental websites where either the full data, or selected subsets corresponding to figures within the paper, can be browsed. We set out to create a CGI application containing many of the features of some of the existing standalone software for the visualization of clustered microarray data. RESULTS: We present GeneXplorer, a web application for interactive microarray data visualization and analysis in a web environment. GeneXplorer allows users to browse a microarray dataset in an intuitive fashion. It provides simple access to microarray data over the Internet and uses only HTML and JavaScript to display graphic and annotation information. It provides radar and zoom views of the data, allows display of the nearest neighbors to a gene expression vector based on their Pearson correlations and provides the ability to search gene annotation fields. CONCLUSIONS: The software is released under the permissive MIT Open Source license, and the complete documentation and the entire source code are freely available for download from CPAN