Biomedical subjects

K Glass

Publications and source records attributed to K Glass.

At least 19 recordsLinked to original sources

PubMed2007

Predicting case numbers during infectious disease outbreaks when some cases are undiagnosed.

We describe a method for calculating 95 per cent bounds for the current number of hidden cases and the future number of diagnosed cases during an outbreak of an infectious disease. A Bayesian Markov chain Monte Carlo approach is used to fit a model of infectious disease transmission that takes account of undiagnosed cases. Assessing this method on simulated data, we find that it provides conservative 95 per cent bounds for the number of undiagnosed cases and future case numbers, and that these bounds are robust to modifications in the assumptions generating the simulated data. Moreover, the method provides a good estimate of the initial reproduction number, and the reproduction number in the latter stages of the outbreak. Applying the approach to SARS data from Hong Kong, Singapore, Taiwan and Canada, the bounds on future diagnosed cases are found to be reliable, and the bounds on hidden cases suggests that there were few hidden cases remaining at the end of the outbreaks in each region. We estimate that the initial reproduction numbers lay between 1.5 and 3, and the reproduction numbers in the later stages of the outbreak lay between 0.36 and 0.6.

Bayes Theorem↗

PubMed2006

New methodology for viability testing in environmental samples.

Environmental samples can be complex and are comprised of microorganisms and a matrix of decaying organic matter as well as an inorganic phase such as sand or precipitated material (waste water, sludge, soils, etc.). Nucleic acid dyes have recently been developed to address the growing need for environmental analyses (cell staining, counting, viability testing and specific organism identification). However, certain dyes may not be ideally suited for testing of environmental samples, because they readily adhere to the substrate material as well as their target molecule, resulting in increased non-specific binding and background fluorescence. The aim of this study was to address the limitations of the widely used and commercially available Live/Dead BacLight Bacterial Viability kit (Molecular Probes, Eugene, OR). A new combination of nucleic acid dyes, i.e. SYTO13 and SYTOX Orange (Molecular Probes, Eugene, OR), was proposed as an alternative. The dyes were carefully chosen for their spectral separation and increase of fluorescence quantum yield. A protocol for this combination was first designed and optimized and the two staining assays were compared against suspensions of live and dead E. coli, mixed in different proportions and it was shown that both protocols performed equally on pure cultures. However, when testing activated sludge samples, the commercial kit showed greater background fluorescence and non-specific binding than the alternate combination. Therefore, the proposed dye combination and its corresponding protocol are deemed more suitable for use on complex environmental samples than the Live/Dead BacLight Bacterial Viability kit.

Environmental Microbiology↗

PubMed2006

Evaluation of measures to reduce international spread of SARS.

Mathematical models are used to quantify the effect of border control measures in reducing the international spread of SARS. Border screening is shown to play a relatively minor role in reducing disease spread. Assuming detection rates similar to those reported for arrival screening in Australia, screening can detect up to 10% (95% CI 3-23) of infected travellers, and reduce the probability of a large outbreak by up to 7% (95% CI 2-17). Rapid reductions in the time to diagnosis and effective facilities for the isolation of cases are essential to ensure that there will not be a large outbreak, and each week of delay in responding to imported infection approximately doubles the total number of cases. While the control response is being developed in a currently uninfected region, border screening can provide up to one week's additional time in which to improve methods for early isolation of cases.

Australia↗

PubMed2005

Ecological mechanisms that promote arbovirus survival: a mathematical model of Ross River virus transmission.

Many assessments of host and vector competence for arboviruses focus on level and length of infectivity and ignore ecological mechanisms that contribute to virus survival. In this paper, mathematical models are used to compare local survival mechanisms for a range of scenarios, using Ross River virus as a case study. Ross River virus is an Australian arbovirus with many mosquito vectors and reservoir hosts. The mechanisms for maintaining long-term transmission of the virus vary between salt and freshwater mosquito vectors, and according to the availability of susceptible hosts. The models demonstrate that overwintering of virus in adult freshwater mosquitoes requires a large host population, while overwintering of virus in infected eggs of saltwater mosquitoes is an effective survival strategy when filial infection rates are high. The virus survives longer when both salt and freshwater mosquito species are included in the model than when only one mosquito species is present. When the marsupial host is replaced by a host with higher birth rate and shorter infectious period, the virus survived longer under all models. This suggests that birth rate can be a key factor when assessing the competence of reservoir hosts to maintain virus transmission.

Aedes↗

PubMed2004

Waning immunity and subclinical measles infections in England.

Following the introduction of vaccination against measles, levels of clinical infection have dropped markedly. As we move further into the vaccine era, increasingly many individuals owe their measles immunity to vaccination and have had few (if any) exposures to wild virus. A number of recent reports suggest that vaccinated individuals with low levels of immunity may be at risk of subclinical measles infection. We explore the interplay between levels of infection and immunity over time using a mathematical model that simulates infection, waning and boosting of immunity. We focus particularly on the situation in England, where vaccination has been in place since 1966. Simulations of our model demonstrate a rise in the levels of subclinical measles infection over time, and a corresponding rise in clinical measles infections if vaccination levels are too low. We compare the impact of intervention strategies, and find that the rise in cases is most effectively reduced by 'catch-up' vaccination of children. In recent years, vaccination levels in England have dropped from above 90% in the 1990s to 84% in 2001/2002. We discuss the impact of declining vaccination levels on clinical and subclinical infections.

Antibodies, Viral↗

PubMed2004

The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population.

We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross-reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine-induced level of cross-reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring.

Animals↗

PubMed2004

The effect of heterogeneity in measles vaccination on population immunity.

High overall vaccination levels sometimes hide pockets of poor coverage. We adopted a meta-population framework to model local aggregation of populations, and used this to investigate the effects of vaccination heterogeneity. A recent survey of antibody levels in a community with low vaccination levels in The Netherlands enabled us to assess the relative importance of local and long-range infective contacts, and thus identify feasible levels of aggregation in the meta-population model. In the aggregated model, we found that heterogeneity in vaccination coverage can lead to a much increased rate of infection among unvaccinated individuals, with a simultaneous drop in the average age at infection.

Humans↗

PubMed2003

Interpreting time-series analyses for continuous-time biological models--measles as a case study.

An increasing number of recent studies involve the fitting of mechanistic models to ecological time-series. In some cases, it is necessary for these models to be discrete-time approximations of continuous-time processes. We test the validity of discretization in the case of measles, where time-series models have recently been developed to estimate ecological parameters directly from data. We find that a non-homogeneous contact function is necessary to capture the host-parasite interaction in a discrete-time model, even in the absence of heterogeneities due to spatial or age structure. We derive a mathematical relationship describing the expected departure from mass-action transmission in terms of the epidemiological parameters in the model, and identify conditions under which the discretization process may fail.

Birth Rate↗

PubMed2003

Antibody dynamics in childhood diseases: waning and boosting of immunity and the impact of vaccination.

The introduction of vaccination against acute diseases such as measles induced a dramatic decline in the prevalence of the disease, and a more gradual rise in the proportion of the population whose immunity is derived solely from vaccination. These two factors combine to constitute an important shift in the dynamics of immunity, especially in highly vaccinated populations. We develop a general model to describe both loss of immunity in the absence of disease, and boosting of immunity corresponding to subclinical infection in individuals whose immunity has waned. We consider the interaction between infection and immunity and identify the key parameters that determine the eradication threshold. We explore the dynamics in the years following the introduction of vaccination using a stochastic version of the model, and consider the effect of different assumptions concerning the nature of immunity. A comparison of the model results with recently published data suggests that heterogeneity in host immune response is an important feature of the antibody dynamics.

Antibodies, Viral↗

PubMed2002

Modelling equine influenza 1: a stochastic model of within-yard epidemics.

This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level implies that less virus will be shed during the infectious period, we identify a high degree of heterogeneity in the response of horses with similar pre-challenge antibody levels. We develop a modified model that incorporates some heterogeneity in levels of infectivity, and compare this with the simpler model.

Animals↗

PubMed1997

A medical school's plan for anti-tobacco-use education in community schools and hospitals.

BACKGROUND: Tobacco use in the United States remains a significant health concern. In 1992, students at Dartmouth Medical School began a community service program that targeted the prevention of local tobacco use. METHODS: The program combined primary prevention, through education of school-aged children, with secondary prevention, through smoking cessation clinics. RESULTS: The program has received widespread community as well as national support for its actions. The program is in its initial stages of gathering data to determine whether there has been a significant impact on the tobacco use of the community. CONCLUSIONS: This paper is an introduction to the program's efforts, and a potential template for other medical schools to follow.

Adolescent↗

PubMed1994

Ethical issues involved in establishing a registry for familial Alzheimer's disease.

In January 1992, the IMAGE Project extended the establishment of its registry of familial Alzheimer cases to all areas of the province of Quebec, for collection of epidemiological and clinical data, as well as biological samples. The aim is to study genetic transmission patterns of Alzheimer's disease (AD) and to provide a sampling framework for further etiologic and risk factor studies. The IMAGE registry already includes data of a population-based study in the Saguenay-Lac-St-Jean area; the project to collect data on familial AD (FAD) cases across the province of Quebec is known as the ALGENE Initiative. The registry is thus a collection of "AD families" for both familial and sporadic cases. The establishment of the registry involves several steps in the field work: recruitment and selection of families; collection of information on family medical history; selection of informative families and genetic testing for AD/FAD by linkage analysis. As AD is not homogeneous in its etiology and since we do not know if, in the event that genetics is involved in AD whether or not penetrance of the gene(s) is high, we must be aware of the "genetic horizons" of AD in collecting and conserving data on families of cases, and in the genetic testing for AD/FAD by linkage analysis. Families who choose genetic testing must be aware of the implications of our undertaking, assured of the confidentiality of the test and, at the same time, they must understand its limitations. The experimental nature of our research project raises ethical dilemmas. This article examines these initial considerations of the field work involved in developing a registry pertaining to genetic testing for AD/FAD by linkage analysis and offers some preliminary observations on the experience of the first year of this project.

Aged↗

PubMed1992

An approach to determining the kinematic parameters of biomechanical systems with applications to the wrist.

This paper presents an accurate and robust approach for determining the kinematic parameters of biomechanical systems. A computationally efficient algorithm is given for estimating the translation vector and rotation matrix of a moving body from measurements of the position of at least four spatially distributed points on the body. This algorithm provides an estimation of the spatial location and orientation of the body which is less sensitive to measurement error than other methods. It is indicated how the kinematic parameters can be used to determine the linear translation and angular rotation of the moving body in terms of an anatomically relevant coordinate system. The design, fabrication and calibration of an inexpensive, serial-link, three-dimensional mechanical digitizer for use in data acquisition is described. This device is kinematically optimized and is easy to use for accurate data collection. An implementation of this approach to quantifying certain aspects of the kinematics of the human wrist is discussed.

Algorithms↗

PubMed1990

Evaluation of a fiber optic glove for semi-automated goniometric measurements.

Normal subjects were used to evaluate a fiber optic instrumented glove for semi-automated goniometric measurement. The glove electronically records and transmits hand and finger position to a host computer by measuring the amount of joint flexion. The glove was put through a series of range-of-motion (ROM) tests with five subjects. Metacarpal (MP) and proximal interphalangeal (PIP) joint angles of the five digits were compared during repetitive standardized motions to evaluate the glove's repeatability. The results showed an overall error of 5.6 degrees, as compared to an error of between 5 and 8 degrees with manual measurement. Additional tests were done to determine factors such as fit, grip force, and wrist motion that may contribute to the overall error. The glove should have applicability to some aspects of hand evaluation as a semi-automated goniometric measurement device.

Adolescent↗

PubMed1988

An immunoglobulin heavy chain gene deletion at direct repeats: nucleotide sequence and effect on mRNA accumulation.

The DNA from the mouse myeloma cell, I17, which produces aberrant gamma 2b heavy chain mRNAs, was cloned and sequenced. The I17 mutant, and its parent line 10.1, share a small deletion at the splice junction of the CH1 domain which results in the absence of CH1 sequences from the mRNA. In addition, the genomic DNA of I17 has a deletion of 253 nucleotides which fuses the CH2 and CH3 exons, causes a frameshift of the next 43 amino acids and results in a truncated protein. The deleted nucleotides are flanked by two direct repeats of the CAGCA pentamer in the normal gene. One copy of the repeat and the interposed DNA is removed in the mutant. The DNA deletion is colinear with the mRNA. Both I17 and 10.1 cells have decreased accumulation of the secretory-specific gamma 2b mRNA. The amounts of membrane-specific gamma 2b mRNA are also affected in the mutants.

Animals↗

PubMed1987

Occupational therapists' views about the use of robotic aids for people with disabilities.

The use of robotic aids for persons with disabilities has potential benefits both in terms of cost cutting and improved health care. This article reviews robotic aids currently in use and reports the results of a survey of 51 occupational therapists at four hospitals offering rehabilitation services for patients with spinal cord injuries: Therapists were generally positive about the use of robotic aids and expressed interest in learning more about this technology.

Attitude of Health Personnel↗

PubMed1985

Postmenopausal osteoporosis as a manifestation of renal hypercalciuria with secondary hyperparathyroidism.

An apparently unique presentation of osteoporosis was encountered in eight postmenopausal women (mean age, 56.8 yr). They had renal hypercalciuria, since they had fasting hypercalciuria [0.17 +/- 0.04 (+/- SD) mg/100 ml glomerular filtrate (GF)] in the setting of normocalcemia and parathyroid stimulation (high serum immunoreactive PTH and/or urinary cAMP). Serum 1,25-dihydroxyvitamin D was not significantly different (28 +/- 7 vs. 34 +/- 2 pg/ml) from that in a nonelderly control group, but fractional intestinal calcium (Ca) absorption was significantly lower (0.382 +/- 0.123 vs. 0.49 +/- 0.06; P less than 0.025). Thus, the patients did not have compensatory intestinal hyperabsorption of Ca despite PTH excess. Treatment with hydrochlorothiazide (50 mg/day) produced a decline in fasting urinary Ca (to 0.07 +/- 0.02 mg/100 ml GF; P less than 0.01), serum PTH (from 39 +/- 19 to 21 +/- 1 microliters eq/ml; P less than 0.05), and urinary cAMP excretion (from 5.30 +/- 0.57 to 3.57 +/- 0.59 nmol/100 ml GF; P less than 0.0025). The results suggested that hyperparathyroidism was secondary. Histomorphometric analysis of bone showed reduced trabecular bone volume without mineralization defect, compatible with osteoporosis. Four of eight patients had high or high normal fractional resorption surfaces, fractional formation surfaces, and fractional osteoid volumes. That these abnormalities may reflect PTH-dependent osteoclastic resorption and bone turnover was supported by the reduction of these indices after correction of secondary hyperparathyroidism with hydrochlorothiazide therapy. The remaining four patients, however, had normal histomorphometric results. In summary, postmenopausal osteoporosis may occur sometimes with renal hypercalciuria and secondary hyperparathyroidism. The lack of compensatory intestinal hyperabsorption of Ca predisposes to negative Ca balance, and the hyperparathyroid state may be manifested by stimulated osteoclastic and osteoblastic activities.

Aged↗

PubMed1984

Reduction in intestinal calcium absorption by hydrochlorothiazide in postmenopausal osteoporosis.

In six women with postmenopausal osteoporosis, most of whom responded to 50 micrograms/day 25-hydroxyvitamin D (25-OHD) therapy with a rise in intestinal calcium (Ca) absorption, 50 mg/day hydrochlorothiazide (TZ) were added to determine whether the resulting decline in urinary Ca would cause Ca retention in the skeleton. Urinary Ca decreased from 183 +/- 48 (SD) mg/day to 142 +/- 67 mg/day (P less than 0.05) when TZ was added. However, fractional Ca absorption also declined from 0.532 +/- 0.077 during 25-OHD treatment to 0.401 +/- 0.064 during combined 25-OHD and TZ therapy (P less than 0.0025). The above changes were accompanied by a significant decline in urinary cAMP from 4.29 +/- 1.64 to 3.19 +/- 1.44 mumol/g creatinine (P less than 0.05) and in serum 1,25-dihydroxyvitamin D from 41 +/- 14 to 22 +/- 11 pg/ml (P less than 0.01). The results suggest that TZ lowers urinary Ca, suppresses parathyroid function, inhibits 1,25-dihydroxyvitamin D synthesis, and thereby reduces intestinal Ca absorption. Thus, combined 25-OHD and TZ therapy probably does not improve Ca balance.

Aged↗