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Worksite and communications-based promotion of a local walking path.

Current research has shown relationships between the environment (eg, parks and trails) and levels of physical activity participation. This study was designed to implement and evaluate a communications based worksite campaign to promote awareness of an existing local walking path and to increase walking. Promotional materials were distributed for 1 month via flyers, email, website postings, and during bi-weekly information booths. Evaluations were conducted at baseline, during, and following the promotional campaign. Borderline statistically significant increases in walking activity from baseline were observed midway through the campaign (p = 0.069) and following the campaign (p = 0.075). Counts observed during the intervention were almost triple those at baseline and increased in the post-campaign phase to approximately three and a half times those at baseline. Sign recognition surveys revealed at baseline, 51% of the participants correctly identified the walking path signs, which increased to 65% during the campaign (p = .0674). Familiarity with physical activity messages around the workplace increased from 64.6% at baseline to 75.5% during the campaign (p = .097). This study shows initial promise of a theoretically based communications intervention to increase knowledge of physical activity and to promote walking.

Adult↗

Use of person-years of CIN III exposure as a surrogate outcome measure in cervical cancer screening trials.

BACKGROUND: The reluctance to perform randomised trials on still unresolved issues of the cervical screening programme is largely due to the view that using invasive cancer as an end-point would require huge and lengthy studies. However, by assuming that the incidence of invasive cancer is related to the number of women with CIN III, an estimate of person-years of CIN III can act as a surrogate outcome. METHODS: By having a reliable model for the development of CIN III and the errors involved in taking the smears and biopsies, the person-years of CIN III can be estimated from a smear and biopsy history. Methods for comparing resulting distributions of person-years of CIN III are discussed. Sensitivity analyses on the error rates of smear and biopsy results, and on the incidence of onset and regression of CIN III are performed. RESULTS: Estimates of person-years of CIN III were calculated for women with mildly abnormal smears in two screening programmes. 11% of women in the Cambridge programme and 21% in the Aberdeen programme were estimated to have been exposed to CIN III for more than 12 months. The greater estimated person-years of CIN III in the Aberdeen study reflects the more conservative treatment policy which was operating there. DISCUSSION: The use of person-years of CIN III as a surrogate outcome can provide a practical and meaningful assessment of strategies for cervical cancer screening. Using CIN III, in place of invasive disease, considerably reduces the study duration and sample size required.

Biopsy↗

Using time of first positive HIV test and other auxiliary data in back-projection of AIDS incidence.

Estimation of HIV incidence by the method of back-projection typically uses data on the time of diagnosis of AIDS cases, together with known information about the incubation distribution of AIDS. This paper discusses back-projection using auxiliary data on AIDS cases, particularly the time of first positive HIV test. We discuss the possibility that certain types of auxiliary data, including time of first positive test, can be useful in back-projection because they provide extra information about the incubation period of AIDS cases. Under a back-projection model, theoretical efficiency calculations are given comparing back-projection with and without the time of first positive HIV test of AIDS cases. These calculations suggest that such data have the potential to significantly improve HIV incidence estimates, particularly in the recent past. Smoothed non-parametric estimates of both HIV incidence and time-dependent testing rates are described. These can be obtained using the EM algorithm, in conjunction with a smoothing step or a penalized likelihood. The benefit of these methods in practice needs to be assessed as such data become available.

Acquired Immunodeficiency Syndrome↗

Projection of incidence rates to a larger population using ecologic variables.

There is wide acceptance of direct standardization of vital rates to adjust for differing age distributions according to the representation within age categories of some referent population. One can use a similar process to standardize, and subsequently project vital rates with respect to continuous, or ratio scale ecologic variables. We obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) programme, a 10 per cent subset of the total U.S. population, country-level breast cancer incidence during 1987-1989 for white women aged 50 and over. We applied regression coefficients that relate ecologic factors to SEER incidence to the full national complement of county-level information to produce an age and ecologic factor adjusted rate that may be more representative of the U.S. than the simple age-adjusted SEER incidence. We conducted a validation study using breast cancer mortality data available for the entire U.S. and which supports the appropriateness of this method for projecting rates.

Age Factors↗

The impact of major transformations of a production process on age-related accident risks: a study of an iron-ore mine.

This paper describes a study of whether accident risks were equally distributed across age categories among a population of mining workers whose work activities were suspected to be age-impaired. The impairment factors in focus are the transformation of production technology during the 80s and consequent changes in job content. It was hypothesized that the combined effect of these factors might lead accident risks, both non-specific (aggregated) and specific (by kind), to increase with age. Accident risk ratios (ARRs), however, proved to be higher for younger workers than older ones, in both the non-specific and the specific cases. However, two accident patterns (specific risks) also show relatively high ARRs among workers in their 40s (and even 30s), results that might be explained by particular exposures and/or age-related performance problems. The findings suggest that technological changes designed to increase productivity and reduce staffing levels more rapidly affect efficiency and productivity than they do accident occurrence, and that they penalize young workers in the first instance.

Accidents, Occupational↗

Stochastic optimization of intensity modulated radiotherapy to account for uncertainties in patient sensitivity.

The aim of the present work is to better account for the known uncertainties in radiobiological response parameters when optimizing radiation therapy. The radiation sensitivity of a specific patient is usually unknown beyond the expectation value and possibly the standard deviation that may be derived from studies on groups of patients. Instead of trying to find the treatment with the highest possible probability of a desirable outcome for a patient of average sensitivity, it is more desirable to maximize the expectation value of the probability for the desirable outcome over the possible range of variation of the radiation sensitivity of the patient. Such a stochastic optimization will also have to consider the distribution function of the radiation sensitivity and the larger steepness of the response for the individual patient. The results of stochastic optimization are also compared with simpler methods such as using biological response 'margins' to account for the range of sensitivity variation. By using stochastic optimization, the absolute gain will typically be of the order of a few per cent and the relative improvement compared with non-stochastic optimization is generally less than about 10 per cent. The extent of this gain varies with the level of interpatient variability as well as with the difficulty and complexity of the case studied. Although the dose changes are rather small (<5 Gy) there is a strong desire to make treatment plans more robust, and tolerant of the likely range of variation of the radiation sensitivity of each individual patient. When more accurate predictive assays of the radiation sensitivity for each patient become available, the need to consider the range of variations can be reduced considerably.

Dose-Response Relationship, Radiation↗

HLA-DQ beta typing and non-Asp57 alleles in IDDM and nondiabetic subjects in New Zealand.

OBJECTIVE: To determine the frequency of IDDM risk-associated HLA-DQ beta alleles in New Zealanders with IDDM and nondiabetic control subjects, and to examine these as susceptibility markers in relation to IDDM incidence. RESEARCH DESIGN AND METHODS: HLA-DQ beta typing was conducted in 55 juvenile-onset IDDM subjects diagnosed between 1990 and 1992, and 53 nondiabetic control subjects. Allele typing was conducted by a polymerase chain reaction-restriction fragment-length polymorphism technique. All subjects were residents of Canterbury, New Zealand. IDDM incidence data were obtained from the Canterbury, New Zealand, Diabetes Registry. RESULTS: The frequency of the susceptibility genotype DQ beta *0201/0302 was 43.6 and 5.7% in the IDDM and control groups, respectively, reflecting the increased prevalence of allele 0302 in the IDDM group. Alleles 0301, 0501, and 0602.3 were more prevalent in the control group than the IDDM group. The frequency of non-Asp57 alleles was 90.9 and 61.3% in the IDDM and control groups, respectively. Overall, the HLA-DQ beta allele distribution was similar to reports from other Caucasian populations. The 0- to 19-yr age-specific IDDM incidence rate over the period in which the diabetic subjects were diagnosed was 19.5/100,000 person-yr, the highest levels observed in Canterbury over the last decade. Our relatively high background prevalence of non-Asp57 alleles and high IDDM incidence rates were similar to results from some Scandinavian and other hotspot populations. CONCLUSIONS: HLA-DQ beta alleles are genetic susceptibility markers in New Zealand, and other Caucasian populations. Peak IDDM incidence levels observed in 1990-1992 in our population are in accordance with a high background population prevalence of non-Asp57 alleles. These results suggest that the high Canterbury incidence rates may be due to a large HLA-DQ beta non-Asp57 at-risk population.

Alleles↗

Passive sampler used for simultaneous measurement of breathing zone size distribution, inhalable dust concentration and other size fractions involving large particles.

The particle size-dependent sampling velocity of the passive dust sampler developed by Vinzents (1996) is investigated under field conditions. Microscopical determination of the projected area equivalent diameter is used to quantify particles deposited on the sampler foils. Parameters for a semi-empirical model for particle deposition velocities on upward and forward facing foils are fitted to the data and it is shown that deposition mechanisms other than gravitational settling on the upward facing foil can be neglected. For calculation of airborne mass concentration no information on particle density is needed and only the ratio between the dynamic and volume shape factors needs to be known. Given the sampling velocity, the airborne mass per diameter interval is calculated from samples obtained in the wood industry, from which inhalable dust concentrations are calculated. The results are in line with parallel samples obtained with an inhalable dust sampler. A 'total' dust sampling characteristic can be fitted which reproduces measured 'total' dust with a closed face monitor. The results of this study demonstrate the validity of the passive dust sampling principle in environments involving even large (>100 microm) particles and the potential to predict the concentration of several size fractions.

Air Pollutants, Occupational↗

Plasma cholesterol concentration and mortality. The Whitehall Study.

UNLABELLED: OBJECTIVE--To examine the relationship between plasma cholesterol concentration and mortality from major causes of death. DESIGN: --Cohort study. SETTING--Civil service offices in London, England. PARTICIPANTS--There were 17,718 male civil servants aged 40 through 64 years at the time of study entry between 1967 and 1969. MAIN OUTCOME MEASURE--Mortality from major cause groups. RESULTS--There were 4022 deaths in the cohort over the 18 years of follow-up. Total mortality increased with cholesterol level, although mortality in the small group with very low cholesterol levels (5% of study population) was nonsignificantly higher (P greater than .5) than that of the remainder of the lowest quintile cholesterol group. Coronary heart disease mortality increased with increasing cholesterol concentration from the lowest levels (P less than .001 for trend). The cancer mortality rate in the group below the fifth centile of the cholesterol distribution was higher than in the remainder of the cohort for lung (P less than .001), pancreas (P = .05), liver (P = .09), and all smoking-related cancers (P = .02). Only for lung cancer was there a consistent inverse trend with cholesterol level (P less than .01). Rates of mortality due to non-neoplastic respiratory disease were inversely related to cholesterol level (P less than .001). Health state at the time of examination and socioeconomic position were related to cholesterol concentration--subjects in lower employment grades, with disease at baseline, with a history of recent unexplained weight loss, or who had been widowed had lower initial cholesterol levels. These associations largely accounted for the relationships between cholesterol level and noncardiovascular mortality. CONCLUSIONS--The inverse associations between plasma cholesterol concentration and mortality from certain causes of death seen in cohort studies could be because the participants with low cholesterol levels possess other characteristics that place them at an elevated risk of death.

Adult↗

Variabilities in aerosolizing activities and airborne fungal concentrations in a bakery.

Concentrations of airborne culturable fungi were measured in the kitchen of a bakery in Boston, Mass., to evaluate variabilities associated with common worker activities, outdoor aerosol distributions, and season. Activities were categorized as early morning preparation, cornmeal sifting and tossing, flour dumping and mixing, sweeping, and low activity. Sets of measurements were taken over 1 day in spring and 1 day in summer. Fungal concentrations were measured using a one-stage culture plate impactor, and bulk samples were taken from suspected fungal reservoirs within the bakery and subsequently cultured. Compared with the low activity category, elevated levels of total culturable fungi were found during all other activities, with the amount of increase closely related to individual worker activity as well as outdoor concentrations and initial bakery conditions. In the spring, Penicillium was the dominant genus showing activity-related elevations in concentrations, while Cladosporium was the dominant genus during the summer. Clearly, due to variabilities in worker activities and ambient fungal concentrations, a standardized sampling protocol involving a large sample size over multiple days is needed to estimate accurately exposure to either total airborne fungi or specific fungal taxa.

Aerosols↗

Robust tests for treatment comparisons based on recurrent event responses.

Robust nonparametric tests are considered for use in longitudinal studies in which the response of interest is a recurrent event. The tests are robust in the sense that they do not rely on distributional assumptions regarding the processes generating the events. The methods we describe are presented in the context of a clinical trial with attention initially directed at the two-sample problem in which a single experimental treatment is compared to a control. We investigate a family of generalized pseudo-score statistics (Lawless and Nadeau, 1995, Technometrics 37, 158-168) in which weight functions may be chosen to generate tests sensitive to various types of departure from the null hypothesis that the mean functions for the treatment and control groups are identical. All tests we consider are evaluated by simulation with respect to the type I error rate and power under a variety of practical scenarios. An application involving data from a kidney transplant study illustrates these procedures. For trials with multiple treatment arms, we generalize these approaches and indicate test statistics appropriate for unstructured alternatives and tests based on linear contrasts of the treatment-specific mean functions. Extensions of this methodology for stratified designs are also indicated.

Antibodies↗

Constrained additive ordination.

For several decades now, ecologists have sought to determine the shape of species' response curves and how they are distributed along unknown underlying gradients, environmental latent variables, or ordination axes. Its determination has important implications for both continuum theory and community analysis because many theories and models in community ecology assume that responses are symmetric and unimodal. This article proposes a major new technique called constrained additive ordination (CAO) that solves this problem by computing the optimal gradients and flexible response curves. It allows ecologists to see the response curves as they really are, against the dominant gradients. With one gradient, CAO is a generalization of constrained quadratic ordination (CQO; formerly called canonical Gaussian ordination or CGO). It supplants symmetric bell-shaped response curves in CQO with completely flexible smooth curves. The curves are estimated using smoothers such as the smoothing spline. Loosely speaking, CAO models are generalized additive models (GAMs) fitted to a very small number of latent variables. Being data driven rather than model driven, CAO allows the data to "speak for itself" and does not make any of the assumptions made by canonical correspondence analysis. The new methodology is illustrated with a hunting spider data set and a New Zealand tree species data set.

Animals↗

The geographic distribution of melanoma incidence in Massachusetts, adjusted for covariates.

BACKGROUND: The aims of this study were to determine whether observed geographic variations in melanoma cancer incidence in both gender groups are simply random or are statistically significant, whether statistically significant excesses are temporary or persistent, and whether they can be explained by risk factors such as socioeconomic status (SES) or the percent of the population residing in an urban rather than a rural area. Between 1990 and 1999, 4774 female and 5688 male melanomas were diagnosed in Massachusetts residents. Cases were aggregated to census tracts and analyzed for deviations from random occurrence with respect to both spatial location and time. RESULTS: Thirteen geographic areas that deviated significantly from randomness were uncovered in the age-adjusted analyses of males: five with higher incidence rates than expected and eight lower than expected. In the age-adjusted analyses of females, six areas with higher incidence rates and eight areas with lower than expected incidence rates were found. After adjustment for SES and percent urban, several of these areas were no longer significantly different. CONCLUSION: These analyses identify geographic areas with invasive melanoma incidence higher or lower than expected, the times of their excess, and whether or not their status is affected when the model is adjusted for risk factors. These surveillance findings can be a sound starting point for the shoe-leather epidemiologist.

Age Factors↗

Population density methods for large-scale modelling of neuronal networks with realistic synaptic kinetics: cutting the dimension down to size.

Population density methods provide promising time-saving alternatives to direct Monte Carlo simulations of neuronal network activity, in which one tracks the state of thousands of individual neurons and synapses. A population density method has been found to be roughly a hundred times faster than direct simulation for various test networks of integrate-and-fire model neurons with instantaneous excitatory and inhibitory post-synaptic conductances. In this method, neurons are grouped into large populations of similar neurons. For each population, one calculates the evolution of a probability density function (PDF) which describes the distribution of neurons over state space. The population firing rate is then given by the total flux of probability across the threshold voltage for firing an action potential. Extending the method beyond instantaneous synapses is necessary for obtaining accurate results, because synaptic kinetics play an important role in network dynamics. Embellishments incorporating more realistic synaptic kinetics for the underlying neuron model increase the dimension of the PDF, which was one-dimensional in the instantaneous synapse case. This increase in dimension causes a substantial increase in computation time to find the exact PDF, decreasing the computational speed advantage of the population density method over direct Monte Carlo simulation. We report here on a one-dimensional model of the PDF for neurons with arbitrary synaptic kinetics. The method is more accurate than the mean-field method in the steady state, where the mean-field approximation works best, and also under dynamic-stimulus conditions. The method is much faster than direct simulations. Limitations of the method are demonstrated, and possible improvements are discussed.

Cell Count↗

Effects of mesiodistal inclination of implants on stress distribution in implant-supported fixed prostheses.

PURPOSE: Patterns of von Mises stress values surrounding implants supporting fixed prostheses in the posterior edentulous maxilla were evaluated using 3-dimensional finite element analysis. MATERIALS AND METHODS: Implants were placed in maxillary bone in 2 different configurations. In the first configuration, implants were placed in the first premolar, second premolar, and second molar regions; in the second configuration, implants were placed in the second premolar and second molar regions, and a mesial cantilever was extended to the space of the first premolar tooth on the superstructure. On the implant placed in the socket of the second molar, 3 different inclinations were used (0, 15, and 30 degrees). Loading was applied in the vertical, oblique, and horizontal axes. RESULTS: Inclination of the implant in the molar region was found to result in increased stress. Significant increase in stress on the implant embedded in the premolar region was also seen in the design with the cantilever as compared to the conventional prosthesis design. DISCUSSION: The stress concentrations observed at the neck of the implant were similar to results reported in the literature. CONCLUSION: The highest stress value obtained in the study was 194.2 MPa with oblique loading. This value did not exceed the endurance limit of pure titanium, which is 259.9 MPa.

Cadaver↗

Nationwide cancer family ascertainment using Finnish Cancer Registry data on family names and places of birth for 35,761 prostate cancer patients.

Identification of predisposition loci to complex diseases, such as prostate cancer, requires high-quality family material, the ascertainment of which is often laborious, time-consuming and inaccurate with conventional methods. Here, we describe a new method for rapid, nationwide cancer family ascertainment using Finnish Cancer Registry data on 35,761 prostate cancer cases over a 40-year period. As members of a prostate cancer family are likely to share the same family name and place of birth, we stratified all prostate cancer cases by these 2 parameters (10,721 different names and 596 municipalities). Data were compared with the distribution of family names and places of birth for all 3.3 million Finnish men to derive standardized prevalence ratios (SPRs). A significantly elevated SPR of prostate cancer was detected for 468 (1.6%) of the 28,459 evaluable combinations of family name and place of birth. Of the 20 highest SPR values, 19 corresponded to true nuclear families, most of these having 3 or more affected cases. Two-thirds of our 50 previously established Finnish prostate cancer families were classified among this 1.6% fraction of the highest SPR values. Finally, many of the highest SPR values originated from municipalities in southern and south-western Finland. To explore whether such clusters could highlight local founder effects, we applied genealogical research to link together several families with elevated SPRs and identified an extended family with 20 prostate cancer cases with common ancestors in the early seventeenth century. In summary, a rapid novel method was developed and validated for identification of prostate cancer families from nationwide cancer registry data and for the identification of putative regional founder effects.

Cohort Studies↗

Moment equations and dynamics of a household SIS epidemiological model.

An SIS epidemiological model of individuals partitioned into households is studied, where infections take place either within or between households, the latter generally happening much less frequently. The model is explored using stochastic spatial simulations, as well as mathematical models which consist of an infinite system of ordinary differential equations for the moments of the distribution describing the proportions of individuals who are infectious among households. Various moment-closure approximations are used to truncate the system of ODEs to finite systems of equations. These approximations can sometimes lead to a system of ill-behaved ODEs which predict moments which become negative or unbounded. A reparametrization of the ODEs is then developed, which forces all moments to satisfy necessary constraints. Changing the proportion of contacts within and between households does not change the endemic equilibrium, but does affect the amount of time it takes to approach the fixed point; increasing the proportion of contacts within households slows the spread of the infection toward endemic equilibrium. The system of moment equations does describe this phenomenon, although less accurately in the limit as the proportion of between-household contacts approaches zero. The results indicate that although controlling the movement of individuals does not affect the long-term frequency of an infection with SIS dynamics, it can have a large effect on the time-scale of the dynamics, which may provide an opportunity for other controls such as immunizations to be applied.

Computer Simulation↗

An examination of the stress distribution in a soft-lined acrylic resin mandibular complete denture by finite element analysis.

PURPOSE: The aim of this study was to calculate the effect of a soft liner on stress distribution within a mandibular complete denture. Although patients have welcomed soft-lined complete dentures, early fracture is one of the main reasons for failure. To minimize and prevent prosthesis fracture, the understanding of the stress distribution within a prosthesis is important. MATERIALS AND METHODS: A 3-dimensional finite element model of a mandibular complete denture for a severely reduced residual alveolar ridge was constructed. The stress was calculated with linear static finite element analysis. The stress distribution in the soft-lined acrylic resin mandibular complete denture was compared with that of a conventional acrylic resin denture. The resulting stresses were displayed in terms of von Mises equivalent stress and the major principal stresses according to 5 different loading conditions: vertical loads in premolar, molar, and incisor regions; and oblique loads in premolar and molar regions. RESULTS: Oblique loads produced higher levels of stress in the labial notch regions than vertical loads, where tension was the primary mode of stress. Significantly reduced levels of von Mises stress were calculated in soft-liner layers under all loading conditions. Acrylic resin denture base portions, however, exhibited higher levels of von Mises stress in soft-lined complete dentures. CONCLUSION: Three-dimensional finite element analysis gave a realistic explanation of denture fractures and patient response to mandibular complete dentures with and without soft linings. Control of excess lateral occlusal contact might be helpful to reduce the probability of a fracture in soft-lined mandibular complete dentures.

Acrylic Resins↗