Droplet Epitaxy Image Contrast in Mirror Electron Microscopy.

Image simulation methods are applied to interpret mirror electron microscopy (MEM) images obtained from a movie of GaAs droplet epitaxy. Cylindrical symmetry of structures grown by droplet epitaxy is assumed in the simulations which reproduce the main features of the experimental MEM image contrast, demonstrating that droplet epitaxy can be studied in real-time. It is therefore confirmed that an inner ring forms at the droplet contact line and an outer ring (or skirt) occurs outside the droplet periphery. We believe that MEM combined with image simulations will be increasingly used to study the formation and growth of quantum structures.

Population-based surveillance of asthma among workers in British Columbia, Canada.

INTRODUCTION: Population-based health databases were used for the surveillance of asthma among workers in British Columbia for the period 1999 to 2003. The purpose was to identify high-risk groups of workers with asthma for further investigation, education and prevention. METHODS: Workers were identified using an employer-paid health premium field in the provincial health registry, and were linked to their physician visit, hospitalization, workers' compensation and pharmaceutical records; asthma cases were defined by the presence of an asthma diagnosis (International Classification of Diseases [ICD]-9-493) in these health records. Workers were assigned to an ''at-risk'' exposure group based on their industry of employment. RESULTS: For males, significantly higher asthma rates were observed for workers in the Utilities, Transport/Warehousing, Wood and Paper Manufacturing (Sawmills), Health Care/Social Assistance and Education industries. For females, significantly higher rates were found for those working in the Waste Management/Remediation and Health Care/Social Assistance industries. CONCLUSION: The data confirm a high prevalence of active asthma in the working population of British Columbia, and in particular, higher rates among females compared to males and in industries with known respiratory sensitizers such as dust and chemical exposures.

Characterizing the geometry of InAs nanowires using mirror electron microscopy.

Mirror electron microscopy (MEM) imaging of InAs nanowires is a non-destructive electron microscopy technique where the electrons are reflected via an applied electric field before they reach the specimen surface. However strong caustic features are observed that can be non-intuitive and difficult to relate to nanowire geometry and composition. Utilizing caustic imaging theory we can understand and interpret MEM image contrast, relating caustic image features to the properties and parameters of the nanowire. This is applied to obtain quantitative information, including the nanowire width via a through-focus series of MEM images.

Caustic imaging of gallium droplets using mirror electron microscopy.

We discuss a new interpretation of mirror electron microscopy (MEM) images, whereby electric field distortions caused by surface topography and/or potential variations are sufficiently large to create caustics in the image contrast. Using a ray-based trajectory method, we consider how a family of rays overlaps to create caustics in the vicinity of the imaging plane of the magnetic objective lens. Such image caustics contain useful information on the surface topography and/or potential, and can be directly related to surface features. Specifically we show how a through-focus series of MEM images can be used to extract the contact angle of a Ga droplet on a GaAs (001) surface.

Direct-to-participant feedback and awareness of bone mineral density testing results in a population-based sample of mid-aged Canadians.

UNLABELLED: This population-based study of mid-aged Canadians assessed awareness of diagnosis by bone mineral density (BMD) following dual-energy X-ray absorptiometry (DXA) testing and compared the effects of feedback only to the physician with direct-to-participant feedback. Poor recall of osteoporosis results was observed irrespective of the feedback destination, but direct-to-participant feedback improved recall of borderline or normal results. INTRODUCTION: BMD testing provides information about fracture risk. This study assessed whether awareness of results, in a random population sample of mid-aged Canadians, differed if results were provided to physicians only or directly to participants. METHODS: Prospective cohort study of 2,678 women and men aged 40-60 years from the Canadian Multicentre Osteoporosis Study. Participants completed hip and spine DXA and interviewer-administered questionnaires regarding demographics and osteoporosis risk factors. Lateral spine X-rays were conducted on those > or =50 years of age. All test results were reported to the participant, the family physician or both. Associations between BMD results, feedback destination and correct self-report results, 3 years later, were assessed using logistic regression while adjusting for potential confounders. RESULTS: Only 25% of men and 33% of women correctly reported their osteoporosis diagnoses. Direct-to-participant vs. physician-only reports did not improve recall of osteoporosis diagnosis but improved recall of borderline or normal BMD. Older (vs. younger) men and men with prevalent vertebral fractures demonstrated better recall of their osteoporosis diagnosis. CONCLUSIONS: Recall of low BMD results was poor, despite direct-to-participant feedback and even in the presence of other osteoporosis risk factors. Direct-to-participant feedback may improve awareness of borderline or normal BMD results.

Phase retrieval low energy electron microscopy.

We consider the utility of phase-retrieval methods in low energy electron microscopy (LEEM). Computer simulations are presented, demonstrating recovery of the terraced height profile of atomic steps. This recovery uses phase retrieval to decode a single LEEM image, incorporating the effects of defocus, spherical aberration and chromatic aberration. The ability of the method, to obtain temporal sequences of evolving step profiles from a single LEEM movie, is discussed.

Early changes in respiratory health in trades' apprentices and physician visits for respiratory illnesses later in life.

OBJECTIVES: An inception cohort of trades' apprentices had rapid declines in lung function (forced expiratory volume in 1 s (FEV(1))) and rapid increases in bronchial responsiveness ( upward arrowBR) over the first 2 years of employment. We used physician visit data to assess respiratory health over the following 13 years. METHODS: Construction painter, electrician, insulator and machinist apprentices beginning at a British Columbia trade school in 1988 were invited to participate and were followed up 2 years later. Subjects were linked to provincial medical databases to examine physician visits for asthma and other respiratory illnesses for the 13 years following. Multivariable models with rapid decline in FEV(1) and rapid increase in BR from years 1 to 3 were constructed. Respiratory symptoms were also examined as predictors of visit rates and meeting a case definition (for asthma or other respiratory illness). RESULTS: The cohort included 281 apprentices (97% are men). Sixteen subjects met the asthma case definition (>or=2 visits coded as asthma in 1 year) and 20 met the other respiratory illness case definition (>or=3 visits for bronchitis, emphysema, respiratory symptoms in 1 year). In models controlling for demographic factors and smoking, subjects with bronchitis symptoms at baseline were more likely to develop other respiratory illness during follow-up (RR 4.4, 95% CI 1.6 to 11.9). Apprentices who developed asthma symptoms over the first 2 years were approximately six times more likely to become asthma cases (95% CI 1.9 to 18.8). Those with a rapid increase in BR were at increased risk of becoming asthma cases (RR 5.5, 95% CI 1.9 to 16.1), as well as having higher asthma visit rates (RR 6.5). Subjects with rapid decline in FEV(1) were 3.2 times more likely to become asthma cases (95% CI 0.8 to 12.1). CONCLUSIONS: Changes in respiratory health early in adulthood, especially increased BR, are associated with respiratory physician visits. These findings are important for workplace screening and prevention and also suggest that physician visit databases are promising research tools in respiratory epidemiology.

A retrospective assessment of occupational noise exposures for a longitudinal epidemiological study.

OBJECTIVES: Chronic exposure to high levels of noise may be associated with increased risk of cardiovascular disease. We therefore undertook a quantitative retrospective exposure assessment using predictive statistical modelling to estimate historical exposures to noise among a cohort of 27,499 sawmill workers as part of an investigation of acute myocardial infarction mortality. METHODS: Noise exposure data were gathered from research, industry and regulatory sources. An exposure data matrix was defined and exposure level estimated for job title/mill/time period combinations utilising regression analysis to model determinants of noise exposure. Cumulative exposure and duration of exposure metrics were calculated for each subject. These were merged with work history data, and exposure-response associations were tested in subsequent epidemiological studies, reported elsewhere. RESULTS: Over 14,000 noise measurements were obtained from British Columbia sawmills. A subset, comprising 1901 full-shift dosimetry measurements from cohort mills was used in producing a predictive model (R(2) = 0.51). The model was then used to estimate noise exposures for 3809 "cells" of an exposure data matrix representing 81 jobs at 14 mills over several decades. Various exposure metrics were then calculated for subjects; mean cumulative exposure was 101 dBA*year. Mean durations of employment in jobs with exposure above thresholds of 85, 90 and 95 dBA, were 9.9, 7.0 and 3.2 years, respectively. CONCLUSIONS: The utility of predictive statistical modelling for occupational noise exposure was demonstrated. The model required input data that were relatively easily obtained, even retrospectively. Remaining issues include adequate handling of the use of hearing protectors that likely bias exposure estimation.

Risks for the development of outcomes related to occupational allergies: an application of the asthma-specific job exposure matrix compared with self-reports and investigator scores on job-training-related exposure.

BACKGROUND AND AIM: Risks for development of occupational sensitisation, bronchial hyper-responsiveness, rhinoconjunctival and chest symptoms at work associated with continued exposure to high molecular weight (HMW) allergens were estimated with three exposure assessment methods. METHODS: A Cox regression analysis with adjustment for atopy and smoking habit was carried out in 408 apprentices in animal health technology, pastry making, and dental hygiene technology with an 8-year follow-up after training. The risk of continued exposure after training, estimated by the asthma-specific job exposure matrix (JEM), was compared with self-reports and investigator scores on job-training-related exposure. Associations between outcomes and work duration in job(s) related to training were also evaluated. RESULTS: Exposure to animal-derived HMW allergens, subsequent to the apprenticeship period, as estimated by the JEM, was associated with a significantly increased risk for occupational sensitisation (hazard ratio (HR) 6.4; 95% CI 2.3 to 18.2) and rhinoconjunctival symptoms at work (HR 2.6; 95% CI 1.1 to 6.2). Exposure to low molecular weight (LMW) agents significantly increased the risk of developing bronchial hyper-responsiveness (HR 2.3; 95% CI 1.1 to 5.4). Exposure verification appeared to be important to optimise the sensitivity and the specificity, as well as HRs produced by the JEM. Self-reports and investigator scores also indicated that further exposure to HMW allergens increased the risk of developing occupational allergies. The agreement between self-reports, investigator scores, and the JEM were moderate to good. There was no significant association between respiratory outcomes and work duration in jobs related to training. CONCLUSION: The asthma-specific JEM could estimate the risk of various outcomes of occupational allergies associated with exposure to HMW and LMW allergens, but it is relatively labour intensive. Exposure verification is an important integrated step in the JEM that optimised the performance of the matrix.

The Role of Plasmalemmal-Cortical Anchoring on the Stability of Transmembrane Electropores.

The structure of eukaryotic cells is maintained by a network of filamentous actin anchored subjacently to the plasma membrane. This structure is referred to as the actin cortex. We present a locally constrained surface tension model for electroporation in order to address the influence of plasmalemmal-cortical anchoring on electropore dynamics. This model predicts that stable electropores are possible under certain conditions. The existence of stable electropores has been suggested in several experimental studies. The electropore radius at which stability is achieved is a function of the characteristic radii of locally constrained regions about the plasma membrane. This model opens the possibility of using actin-modifying compounds to physically manipulate cortical density, thereby manipulating electroporation dynamics. It also underscores the need to improve electroporation models further by incorporating the influence of trans-electropore ionic and aqueous flow, cortical flexibility, transmembrane protein mobility, and active cellular wound healing mechanisms.

Quantification of electroporative uptake kinetics and electric field heterogeneity effects in cells.

We have conducted experiments quantitatively investigating electroporative uptake kinetics of a fluorescent plasma membrane integrity indicator, propidium iodide (PI), in HL60 human leukemia cells resulting from exposure to 40 mus pulsed electric fields (PEFs). These experiments were possible through the use of calibrated, real-time fluorescence microscopy and the development of a microcuvette: a specialized device designed for exposing cell cultures to intense PEFs while carrying out real-time microscopy. A finite-element electrostatic simulation was carried out to assess the degree of electric field heterogeneity between the microcuvette's electrodes allowing us to correlate trends in electroporative response to electric field distribution. Analysis of experimental data identified two distinctive electroporative uptake signatures: one characterized by low-level, decelerating uptake beginning immediately after PEF exposure and the other by high-level, accelerating fluorescence that is manifested sometimes hundreds of seconds after PEF exposure. The qualitative nature of these fluorescence signatures was used to isolate the conditions required to induce exclusively transient electroporation and to discuss electropore stability and persistence. A range of electric field strengths resulting in transient electroporation was identified for HL60s under our experimental conditions existing between 1.6 and 2 kV/cm. Quantitative analysis was used to determine that HL60s experiencing transient electroporation internalized between 50 and 125 million nucleic acid-bound PI molecules per cell. Finally, we show that electric field heterogeneity may be used to elicit asymmetric electroporative PI uptake within cell cultures and within individual cells.

Considering risks to healthcare workers from glutaraldehyde alternatives in high-level disinfection.

Due to concerns over glutaraldehyde's toxicity, two substitutes have recently been introduced; ortho-phthalaldehyde (OPA), and a mixture of hydrogen peroxide and peracetic acid. There is limited information about the health effects for employees from these products. This study assesses the current practices regarding the use of high-level disinfectants in British Columbian hospitals and predicts the relative toxicities of each product. Industry practices were compiled using a comprehensive survey of current practices and decision processes in all hospitals in British Columbia. Of 95 hospitals, 64 returned surveys; 80% of these used high-level disinfection. Among user hospitals, 49% used glutaraldehyde alone and 51% had introduced alternatives. Concern about staff health was the most common reason for substituting, but this was frequently not considered when choosing specific alternatives. Hospitals that involved occupational health, infection control or regional staff in high-level disinfectant decisions used glutaraldehyde alternatives less often. In most hospitals, it was difficult to find individuals who were knowledgeable about the use of disinfectants. Potential health effects associated with each type of high-level disinfectant were assessed by review of the published literature and available manufacturers' data along with qualitative structure-activity relationship analysis. Results indicated that although all products irritate the skin and respiratory tract, OPA is a potential dermal and respiratory sensitizer but hydrogen peroxide and peracetic acid do not cause allergic reactions. Despite little being known about the risks to employees from glutaraldehyde alternatives, their use is widespread. The potential risks of all high-level disinfectants are serious; thus regulators and users are faced with important risk management decisions before and after they have been introduced into the workplace.

Conducting research: practical steps.

Developing a research protocol and obtaining funding for carrying out the research are only the first steps in doing research. Understanding the means to conduct the research is equally important. As research is a joint effort of a team, a mechanism of collaboration must be developed to engage all those with an interest in the research. This includes the community in which the research is to be undertaken, representatives of those who will participate in the research, the academic community who will be involved in the research, and those who will sponsor the research. These individuals can be formed into a 'steering committee' to guide the development, conduct, analysis and communication of the research. Careful consideration must be given to the benefits and risks of the research. These must be precisely spelled out in the research protocol, and all aspects of the research must be independently evaluated for technical competence, accuracy, communication and liability for injury by an ethics review committee. The research must follow precisely the protocol developed. Administrative procedures, including recruitment and management of staff, outlining standard procedures and quality assurance procedures must be clearly outlined and followed. Carefully handling the information collected in a research project is vital to ensuring the quality and validity of the research.

Measurement in epidemiology.

Data (information) are the building blocks of epidemiological research. Careful measurement, recording and handling of information are crucial to the research process. The nature of the data required must be precisely defined and its collection requires the use of reliable tools or instruments. Standardisation of definitions and procedures used in measurement helps to ensure comparability. Care in undertaking measurements and rigorous training of personnel carrying out the measurements help to ensure precision. Special care is necessary to ensure completeness and accuracy in recording the data. Information may be obtained from routine or especially designed forms and evaluated by counting deaths or cases of disease or measures of dysfunction. Questionnaires are a frequently used instrument for collecting information. They should include data identifying the individual being studied, followed by specific questions concerning diseases and determinants. To be useful, such questionnaires must be carefully structured. Diseases are usually compared by calculating 'rates' or 'risks', consisting of numerators (cases, events) and denominators (population). Prevalence and incidence are standard measures of 'risk'. The collection of high quality information (data) and its use to construct estimates of 'risk' or risk ratios form the basis of epidemiology.

Choosing a research study design and selecting a population to study.

Epidemiological studies have been standardised into a group of 'designs'. The descriptive study describes disease by time, place and person and can develop hypotheses about associations between disease and possible determinants. The analytic study tests these hypotheses. The cross-sectional study measures the disease and determinants at a single point in time. The cohort study identifies those within a group with or without a determinant, and observes the occurrence of disease in the two groups. The case-control study identifies a group of patients with a disease and selects a group of persons from the same population who do not have the disease, comparing the presence of a determinant in the two groups. The experimental study, a type of cohort study, is one in which the investigator 'assigns' the determinant (a treatment) to one subgroup in a population and compares the occurrence of a disease between those with and those without the determinant. All such studies must ensure that the comparisons made have relevance to a defined population. This is done by selecting a 'representative' sample from that population. Carefully selecting a study design and population facilitates the creation of new knowledge while avoiding, as far as possible, important errors.

Getting started in research: the research protocol.

To be efficient and precise, research needs a 'road map', called the 'research protocol', which follows a standard format. It includes an abstract, study description, ethical considerations, significance of the study, the budget and a description of the investigators. Study description spells out the study question, the rationale for the study, including previous studies on the subject, the objectives, hypotheses and aims, design and methods, project management, strengths and limitations and a list of references. The objectives, hypotheses and aims are developed by outlining a general research topic (the objective), developing a hypothesis from the broad objective, translating it into the null hypothesis and then listing the steps by which the null hypothesis will be refuted or accepted (the aims). The design and methods describe the type of study to be undertaken, the population in which the study is carried out, including the sample size and statistical power, the selection of subjects, the methods of data collection, and outline of data management and statistical analysis. The detail of the protocol ensures that the study will be carried out successfully and is essential for all health research.

Research methods for promotion of lung health.

The goal of health research is to develop new knowledge for action to improve health. Relevant health research includes study of diseases, their causes and their treatment/prevention as well as structure and utilisation of health services and policies to improve lung health. As resources are not infinite, priorities must be established. These are determined by the relative frequency of a condition, how much dysfunction or disability it produces and whether there are cost-effective means to deal with it. Epidemiology is the discipline used to address these issues. Using it, one can describe the distribution and relative importance of a condition (the descriptive study), identify determinants and define its natural history (the analytical study), assess methods of prevention, cure and amelioration (the experimental study) and evaluate the process and outcome of services (health services or operational research). Epidemiology addresses itself to determining causation among associated variables. Characteristics associated with causation include consistency, strength of association, specificity, dose response, temporal relationship, coherence, and experimental evidence. Epidemiology can truly be described as the 'basic science of public health.' When used strategically, it can create the new knowledge that is the cornerstone for improving the health of the whole population.

Point-of-sale glass bottle recycling: indoor airborne exposures and symptoms among employees.

AIMS: To assess the impact of newly introduced point-of-sale glass bottle recycling on indoor air quality and employee health. METHODS: Airborne exposures and both chronic and acute respiratory and somatic symptoms were surveyed among 226 employees at 36 randomly selected liquor stores with bottle recycling and in-house glass breaking. Each store was visited twice; between visits glass breaking was discontinued for one month in half the stores (selected at random), although bottles were still collected and stored on site. Rates of chronic symptoms were compared to an external, unexposed control population. RESULTS: Geometric mean exposure levels were 0.18 mg/m3 for inhalable particulate matter and 3.6 EU/m3 for endotoxin (270 personal samples); 1064 CFU/m3 for viable fungi (648 area samples). Fungal levels were associated with visibly mouldy bottles being broken, outdoor fungal counts, and uncovered glass bins. Exposures were not altered by the intervention of shutting down glass breaking machinery. Compared to controls, employees reported more work related chronic chest tightness and chronic nasal symptoms. Acute chest symptoms were associated with breaking visibly mouldy bottles, but not with measured fungal counts. Inhalable particulate matter levels >0.2 mg/m3 were associated with acute upper airway irritation. Somatic symptoms were associated with measures of psychosocial job strain. CONCLUSION: Results suggest that this type of recycling programme may generate fungal exposures sufficient to elicit upper airway and chest symptoms.

Expression and prognostic relevance of Mcl-1 in breast cancer.

BACKGROUND: Bcl-2, an anti-apoptotic protein, is frequently associated with favourable prognosis in breast cancer. The potential role of mcl-1, another bcl-2 family member, in breast cancer has not yet been defined. PATIENTS AND METHODS: This study examined the expression of mcl-1 and bcl-2 in 170 cases of invasive primary breast carcinoma, using reverse-transcriptase polymerase chain reaction and immunohistochemical analyses. RESULTS: Expression of bcl-2 mRNA and protein were found to be favourably associated with outcome for patients, supporting a prognostic role for bcl-2 in breast cancer, whereas mcl-1 expression, at the mRNA or protein level, did not correlate with tumour size, grade, lymph node or ER status, age of patient at diagnosis, or disease outcome. CONCLUSION: As these analyses of mcl-1 expression may have co-detected mcl-1(S/deltaTM) (a more recently identified, shorter variant, that may be pro-apoptotic) with the anti-apoptotic wild-type of mcl-1, it is possible that future studies may indicate some significant clinical correlations if the isoforms can be independently investigated.

Interpreting and reporting results.

Creating and disseminating knowledge is the goal of research. This is accomplished through critical analysis of systematically collected and clearly reported information. Critical analysis begins with the simple step of looking at the data collected prior to applying complex statistical analysis to make comparisons. Statistical analysis is approached in a standardised manner, depending on the type of data that has been collected. When a careful, stepwise standardised approach is applied to comparisons needed to address the research question, new knowledge is created and erroneous conclusions avoided. Following careful examination and analysis of the data, critical review is an important additional step to ensure that conclusions are correctly drawn. The process of peer review involved in publishing the research in the scientific literature is an important step to disseminating the new knowledge and ensuring its quality. Research is never complete without submitting it for publication in the peer-reviewed literature.