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Biomedical subjects

James J Collins

Publications and source records attributed to James J Collins.

35 records · Page 2Linked to original sources
PubMed2004

A review and meta-analysis of formaldehyde exposure and leukemia.

Most reviews on the carcinogenicity of formaldehyde have focused on cancers of the respiratory tract because these cancer sites were thought to be most biologically plausible. However, two recent updated large industrial studies have found positive associations between some measures of formaldehyde exposure and increased leukemia, although another recent update of a large study did not find any association. We examine 18 epidemiology studies of workers exposed to formaldehyde where leukemia rates were reported. We summarize the findings across studies by using meta-analytic techniques to calculate the meta-relative risk values (mRR), confidence intervals, and heterogeneity of the risk estimates for several study characteristics. We also determine if publication or reporting biases may be affecting the estimates. We found a small increase in rate of leukemia overall among embalmers (mRR = 1.6, 95%CI 1.2-6.0), and pathologists/anatomists (mRR = 1.4, 95%CI 1.0-1.9). Industrial workers, who have been reported to have the highest formaldehyde exposures, had a mRR of 0.9 (95%CI 0.8-1.0). There was increased risk with increasing exposure in two large industrial studies, although the increased risk is one of these studies was not seen when an external comparison group is used. Also, another large industrial study with more highly exposure workers found decreased risk of leukemia among the highest exposed group. The long latency for leukemia deaths observed in the two industrial studies that reported increased risk was not consistent with a chemical carcinogen such as benzene. We found limited evidence of publication or reporting bias. On balance, these data do not provide consistent support for a relationship between formaldehyde exposure and leukemia risk.

Data Interpretation, Statistical↗
PubMed2004

Communication of epidemiology study results by industry: the Dow Chemical Company approach.

Communicating epidemiology study results to subjects, affected workers, and community members is an important part of compliance and alignment with our company's policies, industry's Responsible Care Principles, and the doctrines of Good Epidemiology Practices. It is the responsibility of the investigators to interpret their research appropriately for each audience, and to assure that all who have a need or right to know get information in a form meaningful to them. We discuss study communication with examples from a recent evaluation of communication efforts within Dow and our experience with occupational and community studies on dioxin. We also discuss how we currently structure worker and community communication based on this experience. Since each Dow protocol must include a communication plan, when we agree to undertake a study, we are also agreeing to communicate study results. Depending upon the nature and type of the study, there may also be some prestudy communication. We encourage all investigators to share the results of their studies more broadly than just scientific publication and plan for the study communication before the study is initiated.

Chemical Industry↗
PubMed2004

Mortality update of workers exposed to acrylonitrile in The Netherlands.

To study the possible carcinogenic effects of acrylonitrile, we updated the follow up of a cohort of 2842 acrylonitrile workers. The comparison group consisted of 3961 workers from a nitrogen fixation plant. Industrial hygiene assessments quantified past exposure to acrylonitrile, 8-hour averages as well as peak exposure, the use of personal protective equipment, and exposure to other potential carcinogenic agents. Standardized mortality ratios were calculated to adjust for the effect of age distribution, length of follow up, and temporal changes in background mortality rates. Cumulative dose-effect relations were determined for 3 exposure categories and 3 latency periods. The results show that no cancer excess seems related to exposure to acrylonitrile. This additional follow up of a cohort of 2842 workers exposed to acrylonitrile further supports the notion that occupational exposures to acrylonitrile that have occurred in the past have not noticeably increased workers' cancer mortality rates.

Acrylonitrile↗
PubMed2004

Reliability and validity of the Stanford Presenteeism Scale.

OBJECTIVE: This study reports the reliability and validity of the 13-item Stanford Presenteeism Scale (SPS). The SPS differs from similar scales by focusing on knowledge-based and production-based workers. METHODS: Data were obtained from administrative and medical claims databases and from a survey that incorporated the SPS, SF-36, and the Work Limitations Questionnaire. RESULTS: Sixty-three percent (7797) of employees responded. Cronbach's alpha (0.83) indicates adequate reliability. Factor analysis identified two underlying factors, "completing work" and "avoiding distraction." Knowledge-based workers load on "completing work" (alpha = 0.97), whereas production-based workers load on "avoiding distraction" (alpha = 0.98). There were significant and positive relationships between the SPS, SF-36, and Work Limitations Questionnaire. CONCLUSIONS: The SPS demonstrates a high degree of reliability and validity and may be ideal for employers who seek a single scale to measure health-related productivity in a diverse employee population.

Absenteeism↗
PubMed2004

A risk assessment for occupational acrylonitrile exposure using epidemiology data.

The extensive data from the Blair et al.((1)) epidemiology study of occupational acrylonitrile exposure among 25460 workers in eight plants in the United States provide an excellent opportunity to update quantitative risk assessments for this widely used commodity chemical. We employ the semiparametric Cox relative risk (RR) regression model with a cumulative exposure metric to model cause-specific mortality from lung cancer and all other causes. The separately estimated cause-specific cumulative hazards are then combined to provide an overall estimate of age-specific mortality risk. Age-specific estimates of the additional risk of lung cancer mortality associated with several plausible occupational exposure scenarios are obtained. For age 70, these estimates are all markedly lower than those generated with the cancer potency estimate provided in the USEPA acrylonitrile risk assessment.((2)) This result is consistent with the failure of recent occupational studies to confirm elevated lung cancer mortality among acrylonitrile-exposed workers as was originally reported by O'Berg,((3)) and it calls attention to the importance of using high-quality epidemiology data in the risk assessment process.

Acrylonitrile↗
PubMed2003

Vibrating insoles and balance control in elderly people.

Somatosensory function declines with age, and such changes have been associated with diminished motor performance. Input noise can enhance sensory and motor function. We asked young and elderly participants to stand quietly on vibrating gel-based insoles, and calculated sway parameters and random-walk variables. In our 27 participants, application of noise resulted in a reduction in seven of eight sway parameters in young participants and all of the sway variables in elderly participants. Elderly participants showed greater improvement than young people in two variables, mediolateral range (p=0.008), and critical mean square displacement (p=0.012). Noise-based devices, such as randomly vibrating insoles, could ameliorate age-related impairments in balance control.

Adult↗
PubMed2003

Inferring genetic networks and identifying compound mode of action via expression profiling.

The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.

Algorithms↗
PubMed2003

Reverse engineering gene networks: integrating genetic perturbations with dynamical modeling.

While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds.

Algorithms↗
PubMed2003

Predicting the dynamic postural control response from quiet-stance behavior in elderly adults.

Human postural sway, as measured by fluctuations of the center of pressure (COP) under the feet of a quietly standing individual, can be characterized as a stochastic process. The fluctuation-dissipation theorem (FDT) provides a linear relationship between the fluctuations of a quasi-static, stochastic system to the same system's relaxation to equilibrium following a perturbation. We applied a similar linear relationship, based on the FDT, to the human postural control system to explore whether anterior-posterior (AP) fluctuations of the COP during quiet stance can be used to predict the AP response of the postural control system to a weak posteriorly directed mechanical perturbation (tug or pull at the waist). We tested 10 healthy elderly (mean age of 69yr) and 10 healthy young (mean age of 25yr) adult subjects. We found that this linear relationship was applicable to the postural control system of all 10 young and eight of the 10 elderly adult subjects. These results suggest that it is possible to predict an individual's dynamic response to a mild perturbation using quiet-stance data, regardless of age. The existence of this FDT-based linear relationship with respect to the human postural control system suggests that, for a given individual, the postural control system may use the same control mechanisms during quiet stance and mild-perturbation conditions, regardless of age.

Adult↗
PubMed2003

Aging, muscle activity, and balance control: physiologic changes associated with balance impairment.

Older adults demonstrate increased amounts of postural sway, which may ultimately lead to falls. The mechanisms contributing to age-related increases in postural sway and falls in the elderly remain unclear. In an effort to understand age-related changes in posture control, we assessed foot center-of-pressure (COP) displacements and electromyographic data from the tibialis anterior, soleus, vastus lateralis, and biceps femoris collected simultaneously during quiet-standing trials from elderly fallers, elderly non-fallers, and healthy young subjects. Both traditional measures of COP displacements and stabilogram-diffusion analysis were used to characterize the postural sway of each group. Regression analyses were used to assess the relationship between the COP measures and muscle activity. Elderly fallers demonstrated significantly greater amounts of sway in the anteroposterior (AP) direction and greater muscle activity during quiet standing compared with the young subjects, while elderly non-fallers demonstrated significantly greater muscle activation and co-activation compared with the young subjects. No significant differences were found between elderly fallers and elderly non-fallers in measures of postural sway or muscle activity. However, greater postural sway in both the AP and mediolateral (ML) directions and trends of greater muscle activity were found in those older adults who demonstrated lower scores on clinical measures of balance. In addition, short-term postural sway was found to be significantly correlated with muscle activity in each of these groups. This work suggests that high levels of muscle activity are a characteristic of age-related declines in postural stability and that such activity is correlated with short-term postural sway. It is unclear whether increases in muscle activity preclude greater postural instability or if increased muscle activity is a compensatory response to increases in postural sway.

Accidental Falls↗
PubMed2002

Noise-enhanced balance control in older adults.

Somatosensory information is critical to balance control and fall prevention in older adults. Recently, it has been shown that low-level input noise (electrical or mechanical) can enhance the sensitivity of the human somatosensory system. In this study, we tested the effect of low-level electrical noise, applied at the knee, on balance control in 13 healthy elderly volunteers. Subjects performed multiple single-legged stance trials with imperceptible electrical noise applied at the knee during half of the trials. Balance performance was characterized using a force platform to measure the displacement of the center of pressure (COP) under the subject's stance foot. Seven sway parameters were extracted from the COP time series. Improved balance was defined as a reduction in postural sway as indicated by decreases in the COP measures. Six of the seven sway parameters decreased with electrical noise. Three of these parameters decreased significantly ( < 0.05), and a fourth parameter was borderline significant. Averaged across subjects, the application of electrical noise resulted in a 3.8% reduction in mediolateral COP standard deviation ( = 0.04), a 5.4% decrease in the maximum anteroposterior COP excursion ( = 0.03), a 3.1% reduction in the COP path length ( = 0.04), and a 7.8% decrease in swept area ( = 0.05). The results suggest that imperceptible electrical noise, when applied to the knee, can enhance the balance performance of healthy older adults. These findings suggest that electrical noise-based devices may be effective in improving balance control in elderly people.

Aged↗
PubMed2002

Reverse engineering gene networks using singular value decomposition and robust regression.

We propose a scheme to reverse-engineer gene networks on a genome-wide scale using a relatively small amount of gene expression data from microarray experiments. Our method is based on the empirical observation that such networks are typically large and sparse. It uses singular value decomposition to construct a family of candidate solutions and then uses robust regression to identify the solution with the smallest number of connections as the most likely solution. Our algorithm has O(log N) sampling complexity and O(N(4)) computational complexity. We test and validate our approach in a series of in numero experiments on model gene networks.

Algorithms↗
PubMed2002

Enhancing tactile sensation in older adults with electrical noise stimulation.

Older adults often suffer from diminished somatosensation stemming from age-related neuropathy. Recently, localized low-level electrical noise stimulation was shown to enhance tactile sensitivity in healthy young subjects. Here, we hypothesized that fine-touch sensitivity in older adults can be similarly improved. Semmes-Weinstein monofilaments were used to evaluate fine-touch sensitivity on the first metatarsal phalangeal joint with four electrical stimulus conditions and a null (no-noise) condition in nine healthy elderly subjects. Electrical noise stimulation resulted in a statistically significant increase in the number of detections below the null-condition detection threshold, for five of the nine subjects, as well as across the entire population. This work suggests that electrical noise-based techniques may enable people to overcome functional difficulties due to age-related sensory loss.

Aged↗
PubMed2002

Synthetic gene network for entraining and amplifying cellular oscillations.

We present a model for a synthetic gene oscillator and consider the coupling of the oscillator to a periodic process that is intrinsic to the cell. We investigate the synchronization properties of the coupled system, and show how the oscillator can be constructed to yield a significant amplification of cellular oscillations. We reduce the driven oscillator equations to a normal form, and analytically determine the amplification as a function of the strength of the cellular oscillations. The ability to couple naturally occurring genetic oscillations to a synthetically designed network could lead to possible strategies for entraining and/or amplifying oscillations in cellular protein levels.

DNA-Binding Proteins↗
PubMed2002

Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. DESIGN: A randomized controlled study. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE: Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.

Adult↗