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PubMed2002

A logistic mixture model for characterizing genetic determinants causing differentiation in growth trajectories.

The logistic or S-shaped curve of growth is one of the few universal laws in biology. It is certain that there exist specific genes affecting growth curves, but, due to a lack of statistical models, it is unclear how these genes cause phenotypic differentiation in growth and developmental trajectories. In this paper we present a statistical model for detecting major genes responsible for growth trajectories. This model is incorporated with pervasive logistic growth curves under the maximum likelihood framework and, thus, is expected to improve over previous models in both parameter estimation and inference. The power of this model is demonstrated by an example using forest tree data, in which evidence of major genes affecting stem growth processes is successfully detected. The implications for this model and its extensions are discussed.

Crosses, Genetic↗
PubMed2000

Nanofabrication of self-assembled monolayers using scanning probe lithography.

This Account focuses on our recent and systematic effort in the development of generic scanning probe lithography (SPL)-based methodologies to produce nanopatterns of self-assembled monolayers (SAMs). The key to achieving high spatial precision is to keep the tip-surface interactions strong and local. The approaches used include two AFM-based methods, nanoshaving and nanografting, which rely on the local force, and two STM-based techniques, electron-induced diffusion and desorption, which use tunneling electrons for fabrication. In this Account we discuss the principle of these procedures and the critical steps in controlling local tip-surface interactions. The advantages of SPL will be illustrated through various examples of production and modification of SAM nanopatterns and their potential applications.

Chemistry↗
PubMed2004

Resolving ability and image discretization in the visual system.

Psychophysiological studies were performed to measure the spatial threshold for resolution of two "points" and the thresholds for discriminating their orientations depending on the distance between the two points. Data were compared with the scattering of the "point" by the eye's optics, the packing density of cones in the fovea, and the characteristics of the receptive fields of ganglion cells in the foveal area of the retina and neurons in the corresponding projection zones of the primary visual cortex. The effective zone was shown to have to contain a scattering function for several receptors, as this allowed preliminary blurring of the image by the eye's optics to decrease the subsequent (at the level of receptors) discretization noise created by a matrix of receptors. The concordance of these parameters supports the optical operation of the spatial elements of the neural network determining the resolving ability of the visual system at different levels of visual information processing. It is suggested that the special geometry of the receptive fields of neurons in the striate cortex, which are concordant with the statistics of natural scenes, results in a further increase in the signal:noise ratio.

Adult↗
PubMed2001

Investigation of the threshold for allergic reactivity to chromium.

Allergy to chromium is relatively common, often in association with exposure to cement or in leather manufacture. However, in certain locations, there appears to be a relatively large cohort of chromium-sensitive individuals whose allergy cannot be explained by these common sources. In particular, this group include Israeli housewives with persistent hand eczema and concomitant patch test positivity to chromium. The causation of their allergy has been linked with relatively high levels of chromium contamination in household products. To provide further information in respect of the definition of safe levels for such products, we examined 17 chromium-allergic individuals to determine their threshold for reaction under closed patch test and repeated open application test (ROAT) conditions. The data derived indicated that, on normal skin, the patch test threshold was 10 ppm chromium; in the presence of an irritant (sodium lauryl sulfate) the threshold was closer to 1 ppm, 2/17 subjects giving 1+ reactions at this concentration. In the more realistic exposure conditions of the ROAT, 8/14 individuals failed to react to 50 ppm, whilst 3/15 reacted to 5 ppm. Interestingly, there was very poor correlation between patch test sensitivity and ROAT sensitivity. To ensure the large majority of chromium-allergic individuals do not suffer elicitation of their allergy, as well as to limit the development of new chromium-sensitive subjects, it is recommended that household products adhere to a previously published standard of a maximum limit of 5 ppm, with an ultimate target of 1 ppm contamination by chromium.

Adult↗
PubMed2002

Twenty years of mercury monitoring in dental surgeries.

From 1981 to 2001 disposable mercury monitors based on palladium chloride have been deployed in 3,568 dental surgeries throughout the United Kingdom. They have performed well as first-level indicators of high concentrations of mercury vapour in surgeries that had become contaminated by spillage of mercury or faulty equipment. Whilst accumulated data suggests that mercury hygiene practices have improved over the past 20 years, the move to the use of disposable capsules rather than automatic amalgamators does not appear to have been a major factor in this improvement.

Accidents, Occupational↗
PubMed2003

Transcription-independent triggering of the extrinsic pathway of apoptosis by human papillomavirus 18 E2 protein.

Cervical carcinomas are most frequently associated with human papillomaviruses (HPV), whose E6 and E7 oncogenes products induce cellular immortalization. The papillomavirus E2 protein is a transcription factor, which represses the expression of the viral oncogenes, and activates viral DNA replication during the vegetative viral cycle. This protein is specifically inactivated in HPV18-associated carcinoma cells, suggesting that E2 functions prevent carcinogenic progression. Indeed, ectopic expression of E2 in cervical carcinoma cells strongly inhibits cell proliferation. Here we show that above a threshold level of expression, the E2 protein induces apoptosis, independently of other viral functions. The amino-terminal domain is responsible for this apoptotic activity, but surprisingly with no involvement of its transcriptional functions. The death pathway triggered by E2 relies on activation of the initiator caspase 8, specific of the extrinsic pathway of apoptosis. E2 itself is cleaved by caspases during cell death, providing an example of an apoptotic inducer that is itself a target for caspase processing. The autonomous proapoptotic activity of HPV18 E2 described here may counteract the proliferative functions of viral oncogenes, and renders the inactivation of E2 crucial for carcinogenic progression.

Adenoviridae↗
PubMed2001

The control chart: an epidemiological tool for public health monitoring.

The objective of the authors is to apply the control chart, a statistical method for quality control used in industry, to public health surveillance. A pilot study was conducted during the 1998 World Football Cup (WFC) by 553 sentinel general practitioners (GPs) throughout France. The average number of cases of communicable, environmental and societal diseases relating to mass gatherings, and the total number of referrals to hospital reported daily by a GP, were plotted on a u-chart for each condition monitored. This average was beyond the statistical control limits if it fell outside the 99.7% confidence interval of the baseline incidences estimated before the WFC. Seven hundred and forty data points representing 262 279 medical encounters were plotted. Nineteen points exceeded the statistical control limits. None of these alerts was confirmed for two consecutive days. Control charts ensured that the level of the items chosen for general community health surveillance remained under control.

Anniversaries and Special Events↗
PubMed2002

An indirect conductimetric screening method for the detection of antibiotic residues in bovine kidneys.

An indirect conductimetric screening method using three test bacterium-medium combinations was developed for rapid detection of antibiotic residues in bovine carcasses. The detection time (DT), i.e. the point when the growth of the test bacterium was detected, was determined by observing the rate of change in the conductance plotted against time. This detection time averaged half of the reference time recorded by the instrument software. Total change in conductance (TC) was used as a further measure of growth. Threshold values for DT and TC were determined with inhibitor-free kidney samples. The presence of a residue was indicated if the DT exceeded the respective threshold value and was confirmed if the TC remained below the TC threshold value. The limits of detection (LODs) determined with fortified samples were at about or below the MRLs for cephalexin, chlortetracycline, ciprofloxacin, dihydrostreptomycin, enrofloxacin, oxytetracycline and penicillin G. The LODs for penicillin G, oxytetracycline and the sum of enrofloxacin and ciprofloxacin were also estimated with incurred samples; these samples were also analysed using liquid chromatography. The LODs determined with fortified and incurred samples were in close agreement. Given its rapid detection, good sensitivity to a wide range of antibiotics and ease of performance, the indirect conductimetric method developed here would seem to offer an appealing alternative to agar diffusion tests.

Animals↗
PubMed2004

A comparison of X-ray fluorescence and wet chemical analysis of air filter samples from a scrap lead smelting operation.

Personal and area air samples were taken at a scrap lead smelter operation in a bullet manufacturing facility. Samples were taken using the 37-mm styrene-acrylonitrile closed-face filter cassette (CFC, the current US standard device for lead sampling), the 37-mm GSP or "cone" sampler, the 25-mm Institute of Occupational Medicine (IOM) inhalable sampler, and the 25-mm Button sampler (developed at the University of Cincinnati). Polyvinylchloride filters were used for sampling. The filters were pre- and post-weighed, and analyzed for lead content using a field-portable X-ray fluorescence (XRF) analyzer. The filters were then extracted with dilute nitric acid in an ultrasonic extraction bath and the solutions were analyzed by inductively coupled plasma optical emission spectroscopy. The 25-mm filters were analyzed using a single XRF reading, while three readings on different parts of the filter were taken from the 37-mm filters. The single reading from the 25-mm filters was adjusted for the nominal area of the filter to obtain the mass loading, while the three readings from the 37-mm filters were inserted into two different algorithms for calculating the mass loadings, and the algorithms were compared. The IOM sampler was designed for material collected in the body of the sampler to be part of the collected sample as well as that on the filter. Therefore, the IOM sampler cassettes were rinsed separately to determine if wall-loss corrections were necessary. All four samplers gave very good correlations between the two analytical methods above the limit of detection of the XRF procedure. The limit of detection for the 25-mm filters (5 microg) was lower than for the 37-mm filters (10 microg). The percentage of XRF results that were within 25% of the corresponding ICP results was evaluated. In addition, the bias from linear regression was estimated. Linear regression for the Button sampler and the IOM sampler using single readings and the GSP using all tested techniques for total filter loading gave acceptable XRF readings at loadings equivalent to sampling at the OSHA 8-hour Action Level and Permissible Exposure Limit. However, the CFC only had acceptable results when the center reading corrected for filter area was used, which was surprising, and may be a result of a limited data set. In addition to linear regression, simple estimation of bias indicated reasonable agreements between XRF and ICP results for single XRF readings on the Button sampler filters, (82% of the individual results within criterion), and on the IOM sampler filters (77% or 61%--see text), and on the GSP sampler filters using the OSHA algorithm (78%). As a result of this pilot project, all three samplers were considered suitable for inclusion in further field research studies.

Air Pollutants, Occupational↗
PubMed2004

[Threshold].

Explore the source record for details and available documents.

Threshold Limit Values↗
PubMed2006

Effect thresholds and 'adequate control' of risks: The fatal flaws in the EU council's position on authorisation within REACH.

BACKGROUND: Preparation of the new European REACH (Registration, Evaluation and Authorisation of CHemicals) regulation on chemicals has reached a critical stage. Depending on how key elements of the legislative proposal are finalised, especially that on authorisation of uses of 'substances of very high concern', REACH could either provide an effective measure to drive innovation towards cleaner and safer alternatives, or instead lead to further avoidable chemical exposures on the basis of demonstrated 'adequate control' of risks. Given that some key indicators of human and wildlife reproductive health continue to decline in parts of Europe, while evidence for chemical exposure as a contributory factor grows, it will clearly be vital to get the legislation right. GOAL AND SCOPE: Whereas there is now a consensus between the European Parliament and Council of the European Union that uses of persistent, bioaccumulative and toxic (PBT) and very persistent and very bioaccumulative (vPvB) substances should only be permitted when no safer alternatives are available, major differences remain regarding the manner in which other 'substances of very high concern' (including substances which are carcinogenic, mutagenic or toxic to reproduction (CMRs) and endocrine disruptors) are addressed. This paper examines those differences in more detail and proposes some ways forward. METHODS: Using case studies of specific chemicals as examples, the paper critically evaluates the concepts of 'effect thresholds' and 'adequate control' of risks, which underpin the Council's proposal for many CMRs and endocrine disruptors. RESULTS: The subjectivity and uncertainties inherent in the threshold approach proposed by the Council, as illustrated by these case examples, bring its ability to ensure a high level of protection for the environment and human health into question: i. the nature and extent of toxic effects recorded depend on many different factors, including the type of test and conditions selected, the organisms exposed, the timing of exposure and precisely which effects are measured and over what timeframe. ii. doses considerably below 'no effect levels' for survival could nevertheless be causing significant impairment to health and/or reproductive success. iii. chemicals present in mixtures at levels below established thresholds for effects may, in combination, induce significant toxicological responses. DISCUSSION: Under the Council's current proposal, companies will be granted authorisations for some uses of CMRs and endocrine disruptors, even if safer alternatives without these properties are already on the market. The high level of evidence required for identification of substances as being of equivalent concern represents an additional weakness in the Council approach. CONCLUSIONS: Instead, a requirement (along the lines of the Parliament's proposals) to address the availability of alternatives in all cases, to use them when available and to initiate their development when not, represents a more robust, defensible and protective approach to the management of 'substances of very high concern'. The possibility for authorisation of essential uses would remain, while all avoidable uses and exposures would progressively be prevented and sustainable innovation supported. PERSPECTIVES: In the long run, this can only lead to a more sustainable future for the chemical industry in Europe, as well as delivering benefits of increased protection for our environment and health for generations to come.

Conservation of Natural Resources↗
PubMed2001

Noise level measurements in four Phoenix emergency departments.

OBJECTIVE: Our objective was to compare the noise levels in 4 Phoenix-area emergency departments with published safety and comfort standards for noise levels. METHODS: A device used to record sound levels was placed in the nurses' station of 4 Phoenix-area emergency departments for brief periods. Readings were compared with published safety and comfort standards. RESULTS: Noise levels measured in the 4 emergency departments were higher than levels at which one can work comfortably. All the noise levels measured approached or exceeded levels that can cause feelings of annoyance ad other negative effects in individuals. DISCUSSION: A comparison of actual noise levels in 4 local emergency departments with published safety and comfort standards found that 100% of the tested departments were too noisy. Anyone who spends any time exposed to this level of noise is subject to deleterious physical and psychological effects.

Arizona↗
PubMed2005

Postural control and detection of slip/fall initiation in the elderly population.

One of the common causes of morbidity and mortality in workplaces is related to slips or falls. Reaction to external disturbances, such as slips or falls, requires a process of perturbation detection and control of motion changes. Postural control is a common mechanism to compensate unexpected displacements of the body. The ability of postural control diminishes with ageing or neuropathy. In this study, two controlled groups, diabetics and non-diabetics in the elderly population, were investigated to compare how different postural control mechanisms would relate to the detection of perturbation and regain of balance. The ultra-low-vibration Sliding Linear Investigative Platform for Analyzing Lower Limb Stability SYSTEM was used to measure the biomechanical changes of posture and perturbation detection. In phase 1 of the analysis, static measures during quiet standing were considered to investigate the relationship between postural stability and perturbation detection capability. In phase 2 of the analysis, dynamic measures during an occurrence of perturbation were analysed. Statistical tests and linear logistic regression models were applied to find differences of postural control mechanisms and to build a predictive model for perturbation detection quantitatively. It is anticipated that the results of this study will contribute to more comprehensive understanding of postural control mechanisms and design of slip/fall prevention programmes.

Acceleration↗
PubMed1999

Toxicity evaluation of petroleum blending streams: reproductive and developmental effects of light catalytic cracked naphtha distillate in rats.

A distillate of light catalytic cracked naphtha (CAS number 64741-55-5, LCCN-D), administered by inhalation, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, following a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. LCCN-D was administered as a vapor, 6 h/d, 7 d/wk at target concentrations of 0, 750, 2500 or 7500 ppm to female rats for approximately 7 wk from 2 wk prior to mating, during mating through gestational d 19, and to males beginning 2 wk prior to mating for 8 consecutive weeks. Dams and litters were sacrificed on postnatal d 4, and males were sacrificed within the following week. Parental systemic effects observed at the 7500 ppm exposure level were increased kidney weights and relative liver weights in males and increased spleen weights in high-dose females. Livers and spleens from rats in the high-dose group were normal in appearance at necropsy. IncreaSed kidney weights in high-dose males were indicative of male-rat-specific light hydrocarbon nephropathy. No test-related microscopic changes were observed in the reproductive organs or nasal turbinate tissues of either sex. Reproductive performance was unaffected by treatment with LCCN-D. Fertility index was > or =90% in all dose groups. There were no exposure-related differences in implantation sites and live pups per litter, and no gross abnormalities were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was > or =97%; the high-dose group had more male than female pups at birth and at d 4 postpartum. Under the conditions of this study, the no-observable-adverse-effect level (NOAEL) for exposure to light catalytic cracked naphtha distillate for parental toxicity was 2500 ppm and the NOAEL for reproductive performance and developmental toxicity was 7500 ppm.

Alkanes↗
PubMedDate not supplied

Thresholds in chemical carcinogenesis: what are animal experiments telling us?

It appears that the controversy over whether animal experiments demonstrate a threshold for carcinogenicity from chemicals was due to an error in plotting dose response. A linear (arithmetic) scale for the dose of chemicals obscures effects at doses below those used in the experiment and distorts the effect seen over the range of doses used. Gaddum (Nature 156: 463, 1946) pointed out that, empirically, dose should be on a logarithmic scale to effect a linear quantal response. It now is proposed that this logarithmic relationship of dose to effect has a sound basis in chemical thermodynamics (Waddell, Toxicol Sci 68: 275-279, 2002). When the results of major studies (e.g., ED01, etc.) done in the past were reanalyzed with this in mind using the Rozman et al scale (Drug Metab Rev 28: 29-52, 1996), which has a logarithmic scale down to one molecule (10(0)), unequivocal thresholds were demonstrated. Many animal studies now have been reanalyzed by this procedure (e.g., Waddell, Toxicol Sci 72: 158-163, 2003; Waddell, Food Chem Toxicol, in press; Waddell, Hum Exp Toxicol, in press); these studies show thresholds for carcinogenicity at doses ranging from 10(17.1) to 10(21.92) molecules/kg/day. These results require a complete reevaluation of human risk assessment for carcinogenesis from chemicals and a redirection of basic research to discover the system, or systems, that are overwhelmed at these thresholds.

Animals↗
PubMed2005

Thresholds as a unifying theme in regulatory toxicology.

The scientific basis for the US Food and Drug Administration (FDA) threshold of regulation is discussed in relation to its toxicological testing recommendations for food contact substances and the existing methods it employs for exposure estimation. A case is made that the FDA's threshold of regulation is a natural extension of its toxicity testing regime. The genetic toxicity tests recommended in the exposure-based toxicological testing framework for food contact substances are examined regarding their ability to predict positively carcinogens of varying potency. In addition, the computational toxicology program MULTICASE v. 3.1 is also examined for its ability to predict positively carcinogens of varying potency. It is concluded that MULTICASE can provide equivalent results to genetic toxicity tests at the lowest dietary concentrations.

Carcinogenicity Tests↗