Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

Spectral characterization of flash and high flux x-ray radiographic sources with a magnetic Compton spectrometer.

In this work, we present a new analysis method applied to revitalize permanent magnet Compton spectrometers used to measure photon energy spectra in the MeV range. The inversion of the measured electron distribution to determine the original photon distribution is achieved via a method of consistent coupled radiation transport and magnetic field mapping of the input photon spectra to the measured electron distribution. The method of linear least squares was used to perform the unfolding of the electron distribution to the initial photon spectra, without any assumptions made regarding the electron distribution. We present an application of this method to data from a nominal 19.4 MeV flash radiographic source (the first axis of the Dual Axis Radiographic Hydro-Test Facility) capable of generating 500 R @ 1 m in ∼60 ns and a medical therapy source (a Scanditronix M22, Microtron) capable of variable energies with nominal endpoints of 6, 10, 15, and 20 MeV and an output of ∼1000-2000 R/min @ 1 m. The results provide agreement between the modeled and unfolded experimentally measured photon spectra as quantified by statistical tests, from 1.5 to 20 MeV. Experimental results are presented as well as a discussion of the novel MCNP6-based simulations and methods for reconstruction of the spectra.

2,4-Dinitrophenol: 'diet' drug death following major trauma.

There has been a resurgence in the illicit use of 2,4-dinitrophenol by people wishing to achieve rapid weight loss. Despite its availability, the drug is banned for human consumption as it is toxic and can have fatal consequences. We present the case of a 23-year-old man who regularly consumed 2,4-dinitrophenol to generate fat loss without apparent ill effect. He was involved in a high-speed road traffic collision and sustained limb-threatening injuries. The combination of emergency surgery, trauma and 2,4-dinitrophenol consumption culminated in deterioration under anaesthesia, with subsequent death from multiorgan failure in the intensive care unit 48 h later. Previous cases have reported death from 2,4-dinitrophenol toxicity alone. We believe this is the first reported case of 2,4-dinitrophenol toxicity triggered by the additional physiological stress of polytrauma and emergency surgery.

Steering an intense relativistic electron beam in a linear induction accelerator.

The best electron beam transport through a linear induction accelerator (LIA) is achieved when the beam is well centered on the magnetic axis of the focusing solenoids. Since the beam may be injected offset from, or at an angle to, the centerline, dipole magnets are usually provided as a means to steer the beam and center it. Steering may be accomplished by trial and error, but this is very time consuming, especially for accelerators with a low repetition rate for beam position measurements and dipole adjustments. This article presents a steering method requiring a minimal number of measurements and adjustments to position the beam at any desired location, including positioning on the centerline.

Calibration of two compact permanent magnet spectrometers for high current electron linear induction accelerators.

In this work, two compact, permanent magnet, electron spectrometers have been built to measure the electron beam energy at the Dual Axis Radiographic Hydrodynamic Test facility. Using H- and OH- anions, the spectrometers were calibrated at the Special Technologies Laboratory in Santa Barbara, California (USA). The spectrometers were mounted on a custom drift tube that allows the magnet assemblies to be translated, which increases the path length of the electrons traveling through the magnetic field and therefore increases the upper bound of the measurable electron kinetic energy. The measurable range of electron kinetic energies is between 2.8 MeV-4.1 MeV for the first spectrometer and 14.1 MeV-21.1 MeV for the second spectrometer, with an overall measurement uncertainty of 0.32%.

An investigation into exposure of pigs to lead from contaminated zinc oxide in 2007-2008.

BACKGROUND: High levels of lead, up to 3.3 mg/kg fresh weight, were detected in pig liver in Western Australia at the beginning of 2008. This followed the detection of lead at above the maximum level (ML) in a pig liver through the National Residue Survey (NRS). The contamination source was traced back to a zinc oxide feed additive used early post-weaning that contained in excess of 8% lead. METHODS AND RESULTS: Confirmation of the source of lead contamination was obtained by comparing lead isotope ratios for the zinc oxide and the pig livers. The investigation demonstrated the importance of verifying the safety of feed and feed ingredients prior to incorporation in feed. Retrospective analysis of NRS data indicated that the level of lead needed to trigger an investigation for intensively housed pigs should be considerably lower than the ML. As a result, investigations in Australia will now be conducted when levels of lead in pig liver exceed 0.1 mg/kg fresh weight. CONCLUSIONS: Despite the potential for small amounts of non-compliant kidney and liver to enter the human food chain, there was no significant increase in the risk to consumers.

Canadian population risk of radon induced lung cancer: a re-assessment based on the recent cross-Canada radon survey.

Exposure to indoor radon has been determined to be the second leading cause of lung cancer after tobacco smoking. Canadian population risk of radon induced lung cancer was assessed in 2005 with the radon distribution characteristics determined from a radon survey carried out in the late 1970s in 19 cities. In that survey, a grab sampling method was used to measure radon levels. The observed radon concentration in 14,000 Canadian homes surveyed followed a log-normal distribution with a geometric mean (GM) of 11.2 Bq m(-3) and a geometric standard deviation (GSD) of 3.9. Based on the information from that survey, it was estimated that ∼10 % of lung cancers in Canada resulted from indoor radon exposure. To gain a better understanding of radon concentrations in homes across the country, a national residential radon survey was launched in April 2009. In the recent survey, long-term (3 month or longer) indoor radon measurements were made in roughly 14 000 homes in 121 health regions across Canada. The observed radon concentrations follow, as expected, a log-normal distribution with a GM of 41.9 Bq m(-3) and a GSD of 2.8. Based on the more accurate radon distribution characteristics obtained from the recent cross-Canada radon survey, a re-assessment of Canadian population risk for radon induced lung cancer was undertaken. The theoretical estimates show that 16 % of lung cancer deaths among Canadians are attributable to indoor radon exposure. These results strongly suggest the ongoing need for the Canadian National Radon Program. In particular, there is a need for a focus on education and awareness by all levels of government, and in partnership with key stakeholders, to encourage Canadians to take action to reduce the risk from indoor radon exposure.

Soil radon measurements in the Canadian cities.

Radon has been identified as the second leading cause of lung cancer after tobacco smoking. Information on indoor radon concentrations is required to assess the lung cancer burden due to radon exposure. Since radon in soil is believed to be the main source of radon in homes, measurements of soil gas radon concentrations can be used to estimate variations in radon potential of indoor environments. This study reports surveys of natural background variation in soil radon levels in four cities, Montreal, Gatineau, Kingston and the largest Canadian city of Toronto. A total of 212 sites were surveyed. The average soil gas radon concentrations varied significantly from site to site, and ranged from below detection limit to 157 kBq m(-3). For each site, the soil radon potential (SRP) index was determined with the average soil radon concentration and average soil permeability measured. The average SRP indexes are 20±16, 12±11, 8±9 and 12±10 for Montreal, Gatineau, Kingston and Toronto, respectively. The results provide additional data for the validation of an association between indoor and soil radon potentials and for the development of radon potential map of Canada.

Preliminary assessment of thoron exposure in Canada.

Radon has been identified as the second leading cause of lung cancer after tobacco smoking. (222)Rn (radon gas) and (220)Rn (thoron gas) are the most common isotopes of radon. In this study, thoron exposure in Canada was assessed based on three community radon/thoron surveys conducted recently. It was confirmed that thoron was detectable in most homes and thoron progeny were present in every home surveyed. Results demonstrated that thoron concentrations varied more widely than radon. No clear correlation between (222)Rn and (220)Rn concentrations was observed in simultaneous measurements. It is estimated that thoron contributes to about 7 % of the radiation dose due to indoor radon exposure based on measurements in about 260 individual homes. Because indoor measurements and geological gamma-ray surveys did not support a reasonable association between (222)Rn and (220)Rn, thoron concentrations could not be predicted from widely available indoor radon information. In order to better assess thoron exposure in Canada and thoron risk to the Canadian population in various geographic locations, more thoron progeny measurements are required.

Barcoding bacterial cells: A SERS based methodology for pathogen identification.

A principal component analysis (PCA) based on the sign of the second derivative of the surface enhanced Raman spectroscopy (SERS) spectrum obtained on in-situ grown Au cluster covered SiO(2) substrates results in improved reproducibility and enhanced specificity for bacterial diagnostics. The barcode generated clustering results are systematically compared to those obtained from corresponding spectral intensities, first derivatives and second derivatives for the SERS spectra of closely related cereus group Bacillus strains. PCA plots and corresponding hierarchical cluster analysis (HCA) dendrograms illustrate the improved bacterial identification resulting from the barcode spectral data reduction. Supervised DFA plots result in slightly improved group separation but show more susceptibility to false positive classifications than the corresponding PCA contours. In addition, this PCA treatment is used to highlight the enhanced bacterial species specificity observed for SERS as compared to normal bulk (non-SERS) Raman spectra. The identification algorithm described here is critical for the development of SERS microscopy as a rapid, reagentless, portable diagnostic of bacterial pathogens.

Influence of structural and functional modifications of selected genotoxic carcinogens on metabolism and mutagenicity - a review.

Alterations in molecular structure are responsible for the differential biological response(s) of a chemical inside a biosystem. Structural and functional parameters that govern a chemical's metabolic course and determine its ultimate outcome in terms of mutagenic/carcinogenic potential are extensively reviewed here. A large number of environmentally-significant organic chemicals are addressed under one or more broadly classified groups each representing one or more characteristic structural feature. Numerous examples are cited to illustrate the influence of key structural and functional parameters on the metabolism and DNA adduction properties of different chemicals. It is hoped that, in the event of limited experimental data on a chemical's bioactivity, such knowledge of the likely roles played by key molecular features should provide preliminary information regarding its bioactivation, detoxification and/or mutagenic potential and aid the process of screening and prioritising chemicals for further testing.

Characterization of the surface enhanced raman scattering (SERS) of bacteria.

The surface enhanced Raman scattering (SERS) of a number of species and strains of bacteria obtained on novel gold nanoparticle (approximately 80 nm) covered SiO(2) substrates excited at 785 nm is reported. Raman cross-section enhancements of >10(4) per bacterium are found for both Gram-positive and Gram-negative bacteria on these SERS active substrates. The SERS spectra of bacteria are spectrally less congested and exhibit greater species differentiation than their corresponding non-SERS (bulk) Raman spectra at this excitation wavelength. Fluorescence observed in the bulk Raman emission of Bacillus species is not apparent in the corresponding SERS spectra. Despite the field enhancement effects arising from the nanostructured metal surface, this fluorescence component appears "quenched" due to an energy transfer process which does not diminish the Raman emission. The surface enhancement effect allows the observation of Raman spectra of single bacterial cells excited at low incident powers and short data acquisition times. SERS spectra of B. anthracis Sterne illustrate this single cell level capability. Comparison with previous SERS studies reveals how the SERS vibrational signatures are strongly dependent on the morphology and nature of the SERS active substrates. The potential of SERS for detection and identification of bacterial pathogens with species and strain specificity on these gold particle covered glassy substrates is demonstrated by these results.

Subchronic toxicity of chloral hydrate on rats: a drinking water study.

The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 +/- 10 g) and female (190 +/- 8 g) Sprague-Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment-related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment-related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose-related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC(50) of 8 micro M, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment-related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no-observed-effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg(-1) day(-1) in males and 2.53 mg kg(-1) day(-1) in females. This NOEL is ca. 1000-fold higher than the highest concentration of chloral hydrate reported in the municipal water supply.

Chloroform: exposure estimation, hazard characterization, and exposure-response analysis.

Chloroform has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to chloroform principally through inhalation of indoor air, particularly during showering, and through ingestion of tap water. Data on concentrations of chloroform in various media were sufficient to serve as the basis for development of deterministic and probabilistic estimates of exposure for the general population in Canada. On the basis of data acquired principally in studies in experimental animals, chloroform causes hepatic and renal tumors in mice and renal tumors in rats. The weight of evidence indicates that chloroform is likely carcinogenic only at concentrations that induce the obligatory precursor lesions of cytotoxicity and proliferative regenerative response. Since this cytotoxicity is primarily related to rates of formation of reactive, oxidative metabolites, dose response has been characterized in the context of rates of formation of reactive metabolites in the target tissue. Results presented here are from a "hybrid" physiologically based pharmacokinetic (PBPK) animal model that was revised to permit its extension to humans. The relevant measure of exposure response, namely, the mean rate of metabolism in humans associated with a 5% increase in tumor risk (TC05), was estimated on the basis of this PBPK model and compared with tissue dose measures resulting from 24-h multimedia exposure scenarios for Canadians based on midpoint and 95th percentiles for concentrations in outdoor air, indoor air, air in the shower compartment, air in the bathroom after showering, tap water, and food. Nonneoplastic effects observed most consistently at lowest concentrations or doses following repeated exposures of rats and mice to chloroform are cytotoxicity and regenerative proliferation. As for cancer, target organs are the liver and kidney. In addition, chloroform has induced nasal lesions in rats and mice exposed by both inhalation and ingestion at lowest concentrations or doses. The mean rate of metabolism associated with a 5% increase in fatty cysts estimated on the basis of the PBPK model was compared with tissue dose measures resulting from the scenarios already described, and lowest concentrations reported to induce cellular proliferation in the nasal cavities of rats and mice were compared directly with midpoint and 95th percentile estimates of concentrations of chloroform in indoor air in Canada. The degree of confidence in the underlying database and uncertainties in estimates of exposure and in characterization of hazard and dose response are delineated.

Health governance--its introduction in Lanarkshire Health Board.

OBJECTIVE: To describe an approach to implementing the principles of clinical governance in a Health Board setting. DESIGN: Using guidance from the Scottish Executive and The Faculty of Public Health Medicine to set up a health governance structure at Health Board level. Auditing current work to identify areas that required to be progressed. SETTING: Lanarkshire Health Board. RESULTS: A Health Governance Committee and a Health Governance Advisory Group, to support the work of the main committee, were set up at Board level. The Scottish Executive Governance Monitoring Template has been adapted to cover the main public health functions. Topics considered in the first year include qualifications, registration and CPD activity of Consultants in Public Health Medicine, audit of public health advice on gastro-intestinal illness, audit of DPH Annual Report and audit of items of business on Health Board agenda. CONCLUSION: The model developed in Lanarkshire has a Health Governance Advisory Group which works in support of the main Health Governance Committee. This model works well in practice with much of the routine work being done by the Advisory Group. This has streamlined the work of the Health Governance Committee and facilitated its introduction.

Structure-activity relationship study on the bioreduction of azo dyes by Clostridium paraputrificum.

Seven commercially available, structurally related azo dyes have been bioreduced by the anaerobic bacterium Clostridium paraputrificum. The rates of reduction of these dyes were found to vary between 24 and 74 nmoles reduced/mg protein/h. Acid red 1 and desmethyl acid red 106 were found to be the most readily reduced, while chromotrope 2R and cibacron brilliant red 3B-A were reduced at the slowest rates. The differences in reduction rates can be rationalized on the basis of structural differences and are consistent with the possible intermediacy of low molecular-weight electron carriers as the mediators of reduction. The incorporation of electron-withdrawing groups into the dyes, even if remotely placed, was found to increase the rate of reduction of dyes under controlled conditions, supporting the inversely proportional relationship between the electron density of the azo bond and the ease of bioreduction.

Supporting Partners of People with Aphasia in Relationships and Cconversation (SPPARC).

This paper reviews new theoretical and practical developments in working with partners of people with aphasia and describes the development of a clinician's resource entitled 'SPPARC: Supporting Partners of People with Aphasia in Relationships and Conversation'. It focuses particularly on one part of that resource: the SPPARC Conversation Training Programme, which adapts conversation analysis for clinical use. The paper describes the stages involved in assessing and working on conversation in everyday life.

First steps in developing a managed clinical network for vascular services in Lanarkshire.

AIM: To survey key personnel involved in setting up a Managed Clinical Network (MCN) for vascular services in Lanarkshire to assess their views, knowledge and understanding about networking, with a view to facilitating the implementation of the MCN. DESIGN: A questionnaire was designed covering current networking practice, use of protocols, audit and training. It was piloted with the MCN core group and extended to the wider steering group. Semi-structured interviews were completed with core group members focusing on the structure and management of the network. SETTING: Lanarkshire Health Board, Lanarkshire Acute Hospital Trust and Lanarkshire Primary Care Trust. SUBJECTS: The core group and steering group for the development of a Managed Clinical Network for Vascular Surgical Services. RESULTS: Clinicians tend to have more contacts with clinicians and managers with managers. There was close and frequent networking among clinicians of equal status. Respondents shared increased expectations for participation in audit, working to protocols, training and development and improved means of obtaining patients' views and providing information. All respondents recognised the necessity for network leadership although, in this study, it was not possible to define the style of leadership. CONCLUSION: This study identified a degree of existing, informal networking among members of the core group and steering group and it will be important to build on that foundation as the MCN develops. Further research is required to determine the most appropriate form of leadership for the network, and to identify, more clearly, what is understood by a managed network and what accountability there should be.

Needs assessment in primary care: general practitioners' perceptions and implications for the future.

BACKGROUND: Health needs assessment can guide the appropriate shift to primary care by identifying the most effective and efficient resource allocation to meet the needs of populations. Assessing health care needs will be a continuing challenge for primary care trusts in Scotland (or equivalent groups in other parts of the United Kingdom); however, lessons must be learned from the experience of needs assessment that followed the 'internal market' reforms of the 1990s. AIM: To examine general practitioners' (GPs') awareness and experience of needs assessment, to identify barriers to needs assessment in primary care, and to ascertain how better progress might be made in the future. METHOD: A postal questionnaire survey of 1777 Scottish GPs (a one-in-two sample) was combined with a semistructured interview survey of 'lead' GPs from a random sample of 64 mainland Scottish practices between May and August 1996. RESULTS: Sixty-five per cent (1154) of GPs responded to the questionnaire, of which 54% (965) were completed. Over 73% (47) of interviews were completed. Most GPs were unfamiliar with the concept of needs assessment and there was no evidence that needs assessment had influenced commissioning decisions. Most GPs argued that it was not a 'core' activity and that they lacked training in the relevant skills. While the attitude of the majority was indifferent, cynical, and sometimes hostile, a minority, comprising mostly younger fundholders, was more enthusiastic about needs assessment. CONCLUSION: The motivation and attitude of the majority of GPs present a barrier to needs assessment in primary care. GPs will require more resources and training if they are to undertake this responsibility. Most GPs believe than incentives (financial or organisational) will be necessary. Primary care trusts and equivalent structures should be aware of these attitudes as they seek to establish plans based on estimates of population needs in defined locations.

Helicobacter pylori physiology predicted from genomic comparison of two strains.

Helicobacter pylori is a gram-negative bacteria which colonizes the gastric mucosa of humans and is implicated in a wide range of gastroduodenal diseases. This paper reviews the physiology of this bacterium as predicted from the sequenced genomes of two unrelated strains and reconciles these predictions with the literature. In general, the predicted capabilities are in good agreement with reported experimental observations. H. pylori is limited in carbohydrate utilization and will use amino acids, for which it has transporter systems, as sources of carbon. Energy can be generated by fermentation, and the bacterium possesses components necessary for both aerobic and anaerobic respiration. Sulfur metabolism is limited, whereas nitrogen metabolism is extensive. There is active uptake of DNA via transformation and ample restriction-modification activities. The cell contains numerous outer membrane proteins, some of which are porins or involved in iron uptake. Some of these outer membrane proteins and the lipopolysaccharide may be regulated by a slipped-strand repair mechanism which probably results in phase variation and plays a role in colonization. In contrast to a commonly held belief that H. pylori is a very diverse species, few differences were predicted in the physiology of these two unrelated strains, indicating that host and environmental factors probably play a significant role in the outcome of H. pylori-related disease.