Rapporteur report: Mechanisms and interactions

The first two talks of this session described the basic characteristics of the interaction of ultrasound with matter, the first (by V.F. Humphrey) concentrating on the physical interactions, with the second (by W.D. O’Brien, Jr.) focusing on the biophysical effects and mechanisms. The regimes covered by the first and second talks were of primarily high-frequency (O(MHz)) ultrasound in liquids and tissue, respectively. In contrast, the third and final talk of the session (by M. Alves-Pereira) discussed observations made by her group of the vibroacoustic effects of low-frequency noise and infrasound, propagating through air, on humans and animals.     

Rapporteur report: Roundup, discussion and recommendations

There is a relative paucity of recent information regarding the long-term health effects associated with exposure to ultrasound, and to infrasound and low-frequency noise (LFN). For ultrasound, further epidemiological studies are recommended, and priority should be given to studies investigating the effects of handedness and to studies assessing possible subtle effects on brain function. These studies should reflect contemporary practises in diagnostic ultrasound and have sufficiently long follow-up periods to examine the possibility of effects into late adolescence or beyond. In the absence of a non-exposed control group, it would be advisable to make comparisons between a highly exposed group with a less exposed group, and to compare groups exposed at differing gestational stages. The effects associated with ultrasound contrast agents should also be studied, and the appropriateness of the thermal index (TI) and mechanical index (MI) should be reviewed. It is recommended that animal models should be used to investigate the effects of exposure at differing gestational ages on development, and modern cellular and molecular techniques used to investigate potential mechanisms of interaction. Although explicit morphological changes have been reported following occupational and experimental exposures to infrasound and low LFN, it was recommended that a thorough review of the relevant biological and health effects literature was necessary before specific proposals could be made. Uncertainties about the characterisation of these low frequencies also indicated the need to develop appropriate measurement techniques and protocols.     

Medical and non-medical protection standards for ultrasound and infrasound

Protection from inappropriate or hazardous exposure to ultrasound is controlled through international standards and national regulations. IEC standard 60601 part 1 establishes requirements for the mechanical, electrical, chemical and thermal safety for all electro-medical equipment. The associated part 2 standard for diagnostic medical ultrasonic equipment sets no upper limits on ultrasonic exposure. Instead, safety indices are defined that are intended to advise users on the degree of thermal and mechanical hazard. At present the display of these safety indices satisfies regulatory requirements in both the USA and Europe. Nevertheless there are reservations about the effectiveness of this approach to protection management. In the USA, there are national regulatory limits on diagnostic exposure, based on acoustic output from clinical equipment in use over 20 years ago. The IEC 60601 part 2 standard for therapeutic equipment sets 3 W cm⁻² as the limit on acoustic intensity. Transducer surface temperature is controlled for both diagnostic and therapy devices.

For airborne ultrasound, interim guidelines on limits of human exposure published by the IRPA are now 2 decades old. A limit on sound pressure level of 100 dB for the general population is recommended. The absence of protection standards for infrasound relates to difficulties in measurement at these low frequencies.     

Rapporteur report: Epidemiology

Three talks were presented in the session on “Epidemiology”. The first talk was a review of prenatal studies. The second talk presented epidemiological evidence from prenatal studies. The third talk presented general issues regarding the planning of an epidemiological study. It was noted that epidemiological studies of prenatal exposures use data from the early 1980s when ultrasound was first introduced for foetal scans. These studies did not show associations between prenatal ultrasound scanning and childhood cancer, reduced birth weight, impaired childhood growth or neurological development in childhood. However, there was a possible association between prenatal ultrasound scanning and left-handedness in boys. The aetiology of this association remains uncertain.     

Rapporteur report: implications for exposure guidelines

There is a paucity of information regarding the long-term health effects associated with exposure to static magnetic fields. Perceptual and other acute effects have been demonstrated above a threshold of about 2 T, and these form the basis for human exposure standards at present. Exposures well above this threshold are increasingly becoming more common as the technology associated with magnetic resonance imaging advances. Therefore, priority should be given to assessing the health risks associated with exposures to such fields. Studies should include a prospective cohort study investigating cancer risks of workers and patients exposed to fields in excess of 2 T, a study investigating effects on human cognitive performance from repeated exposures, and a molecular biology study investigating acute changes in genomic responses in volunteers exposed to fields of up to 8 T. Studies investigating the effects of long-term exposure on cancer, and on neurobehavioural development are also recommended using animals, where the use of transgenic models is encouraged. In addition, dosimetric studies should be conducted using high-resolution male, female and pregnant voxel phantoms, as should theoretical studies investigating the local currents induced in the eye and in the heart by movement during exposure. Finally, studies are recommended to investigate further the ability of static magnetic fields to significantly affect radical pair reactions in biological systems.     

Standards for biodiversity: a proposal based on biodiversity standards for forest plantations

The 1992 Convention on Biological Diversity has not only focused attention on the concept of biodiversity it has also set expectations that the signatory nations will establish objectives. It is suggested here that the use of biodiversity standards could have a useful role in quantifying these objectives. The use of biodiversity standards is explored in connection with the levels of biodiversity In plantation forests. Forest plantations have been used for the basis of this investigation because such plantations could be used as large-scale experiments in which the use of standards, and the ecological monitoring of these standards, could be researched. The impact of intensive forestry practices on wildlife has often been the cause of concern and indeed controversy. Recently there has been a move towards the development of multipurpose forest plantations where management for recreation and wildlife takes place alongside management for timber. Some forest authorities are actively looking at ways of restoring levels of biodiversity in plantation forests. We suggest that if levels of biodiversity are to be restored, then forest managers must have something to aim for; that is, there must be a standard. The adoption of standards could provide a means whereby forest managers can meet biodiversity objectives. Standards may also enable managers to determine the effectiveness of those management practices which are intended to increase levels of biodiversity. We suggest a conceptual plan which combines a monitoring procedure with biodiversity objectives.     

Rapporteur report: cellular, animal and epidemiological studies of the effects of static magnetic fields relevant to human health

Three talks were presented in the session on “Cellular, Animal and Epidemiological Studies of the Effects of Static Magnetic Fields Relevant to Human Health”. The first talk presented the in vitro effects of static magnetic fields on cell cultures. The second talk presented the in vivo evidence obtained from animal studies. The final, third talk, presented the evidence obtained from epidemiological studies.

The overall conclusion of the three presentations and the following general discussion was that the scientific evidence available to date is weak and contains large gaps in knowledge either due to the poor quality of published studies or because of the lack of published research on certain health-related topics.

It was emphasized that the rapid development of new technological applications of static magnetic fields (e.g. magnetic levitation trains or magnetic resonance imaging—MRI) results in the human population at large, in certain occupations, and in a selected population of clinical patients being exposed to ever increasing static magnetic field strengths. It is of concern that the knowledge presently available concerning the health effects of these strong static magnetic fields is lagging a long way behind technological development.

In conclusion, it was suggested that there is an urgent need to perform new studies in all research areas (in vitro, in vivo and epidemiology) in order to fill the present gaps in knowledge and provide assurance that this technology will not cause any unwanted and unexpected health side effects.     

Water Quality Quantification: Basics and Implementation

Quantitative estimation of water quality and its relationships with management activities is a necessary step in efficient water resources management. However, water quality is typically defined in abstract terms and management activities are rarely quantified with respect to their impact on lake water quality. Here we show by demonstration of systems for Lake Kinneret, Israel and the Naroch Lakes of Belarus how water quality can be quantified in relation to lake management activities to be a part of sustainable management.     

The HUPO proteomics standards initiative--easing communication and minimizing data loss in a changing world

The amount of data currently being generated by proteomics laboratories around the world is increasing exponentially, making it ever more critical that scientists are able to exchange, compare and retrieve datasets when re-evaluation of their original conclusions becomes important. Only a fraction of this data is published in the literature and important information is being lost every day as data formats become obsolete. The Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) was tasked with the creation of data standards and interchange formats to allow both the exchange and storage of such data irrespective of the hardware and software from which it was generated. This article will provide an update on the work of this group, the creation and implementation of these standards and the standards-compliant data repositories being established as result of their efforts.     

Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results

Informatics standards and controlled vocabularies are essentialfor allowing information technology to help exchange, manage,interpret and compare large data collections. In a rapidly evolvingfield, the challenge is to work out how best to describe, butnot prescribe, the use of these technologies and methods. AMetabolomics Standards Workshop was held by the US NationalInstitutes of Health (NIH) to bring together multiple ongoingstandards efforts in metabolomics with the NIH research community.The goals were to discuss metabolomics workflows (methods, technologiesand data treatments) and the needs, challenges and potentialapproaches to developing a Metabolomics Standards Initiativethat will help facilitate this rapidly growing field which hasbeen a focus of the NIH roadmap effort. This report highlightsspecific aspects of what was presented and discussed at the1st and 2nd August 2005 Metabolomics Standards Workshop.      

Clinical standards for growth in height of Belgian boys and girls,aged 2 to 18 years

The present paper presents the first clinical standard for growth in height of Belgian boys and girls, based on purely longitudinal data. Growth charts are provided with centiles of height for age along with growth curves of the typical early, average and late maturing child in the population. These new standards show the classical features of cross-sectional standards, but above that, they also provide information about the variability in individual growth patterns, as a result of variation in maturation. Average adult height is 176.6 cm (SD=6.3 cm) in boys and 163.3 cm (SD=5.7 cm) in girls. The representativity of these new standards with respect to the actual Belgian population has been by comparison with recent cross-sectional data, collected on a large number of subjects. These standards should be applied in all situations where interest lies in the evaluation of the normality of a child's growth pattern over some length of time and will therefore find their usefulness in clinical follow-up studies of growth.     

Data standards for proteomics: mitochondrial two-dimensional polyacrylamide gel electrophoresis data as a model system

Proteomics has emerged as a major discipline that led to a re-examination of the need for consensus and a nationally sanctioned set of proteomics technology standards. Such standards for databases and data reporting may be applied to two-dimensional polyacrylamide gel electrophoresis (2D PAGE) technology as a pilot project for assessing global and national needs in proteomics, and the role of the National Institute of Standards and Technology (NIST) and other similar standards and measurement organizations. The experience of harmonizing the heterogeneous data included in the Protein Data Bank (PDB) provides a paradigm for technology in an area where significant heterogeneity in technical detail and data storage has evolved. Here we propose an approach toward standardizing mitochondrial 2D PAGE data in support of a globally relevant proteomics consensus.     

FDA and NIST collaboration on standards development activities supporting innovation and translation of regenerative medicine products

The development of standards for the field of regenerative medicine has been noted as a high priority by several road-mapping activities. Additionally, the U.S. Congress recognizes the importance of standards in the 21st Century Cure Act. Standards will help to accelerate and streamline cell and gene therapy product development, ensure the quality and consistency of processes and products, and facilitate their regulatory approval. Although there is general agreement for the need of additional standards for regenerative medicine products, a shared understanding of standards is required for real progress toward the development of standards to advance regenerative medicine. Here, we describe the roles of standards in regenerative medicine as well as the process for standards development and the interactions of different entities in the standards development process. Highlighted are recent coordinated efforts between the U.S. Food and Drug Administration and the National Institute of Standards and Technology to facilitate standards development and foster science that underpins standards development.     

Clinical standards for growth velocity in height of Belgian boys and girls,aged 2 to 18 years

The present paper presents the first clinical standards for growth velocity in height of Belgian boys and girls, based on purely longitudinal data. Growth charts are provided with centiles of height for age, along with the growth velocity curves of the typical early, average and late maturing child in the population. These new growth velocity standards provide centile lines which allow to judge whether a child's growth velocity over a one-year interval lies within the limits of normal variation for his age, irrespective of his stage of maturation. They also provide information about variability in the individual patterns of growth velocity in the population and can, as such, also be used to evaluate the normality of a child's pattern in growth velocity over a longer period of time. Age at peak velocity occured in 95% of the children within an age range of about 4 years. The average age at peak height velocity at puberty was 14.0 years (S.D.=1.0) in boys and 11.6 years (S.D.=0.9) in girls. Peak height velocity was in the average 9.1 cm/year (S.D.=1.4) in boys and 7.5 cm/year (S.D.=1.1) in girls. The representativity of these new standards with respect to the actual Belgian population was tested by comparison with recent cross-sectional data, collected on a large number of subjects. These new charts will find useful applications in longitudinal health screening surveys, and in clinical follow-up studies, where interest lies in the examination of a child's growth retardation in relation to some disease, or catch-up growth, as a response to subsequent medical treatment.     

Metabolomics standards initiative: ontology working group work in progress

In this article we present the activities of the Ontology Working Group (OWG) under the Metabolomics Standards Initiative (MSI) umbrella. Our endeavour aims to synergise the work of several communities, where independent activities are underway to develop terminologies and databases for metabolomics investigations. We have joined forces to rise to the challenges associated with interpreting and integrating experimental process and data across disparate sources (software and databases, private and public). Our focus is to support the activities of the other MSI working groups by developing a common semantic framework to enable metabolomics-user communities to consistently annotate the experimental process and to enable meaningful exchange of datasets. Our work is accessible via a public webpage and a draft ontology has been posted under the Open Biological Ontology umbrella. At the very outset, we have agreed to minimize duplications across omics domains through extensive liaisons with other communities under the OBO Foundry. This is work in progress and we welcome new participants willing to volunteer their time and expertise to this open effort. See the MSI Ontology Working Group website for a complete list of members and contributors. Web URL:     

Cultural and health influences on building,housing, and community standards: Cost implications for the human habitat

International research and practices are reviewed with regard to cultural, social, economic, health, and physical-technological features of needs, standards, and codes regulating the residential environment. Housing and building codes, as well as zoning and subdivision ordinances, are influenced by nonscientific considerations that have significant cost and other policy implications. Noxious and promotive influences are examined for public health codes regulating potable water, waste disposal, and safety in the home, as well as density and congestion for cities, neighborhoods, and individual dwelling units. Density is distinguished from congestion, and the policy implications of both are examined. Cost-benefit ratios indicate that many standards can be appreciably lowered. Vague definitions of health, as adopted by WHO, also invite costinducing moral judgments.     

Rapid synthesis of partially O-methylated alditol acetate standards for GC-MS: some relative activities of hydroxyl groups of methyl glycopyranosides on Purdie methylation

Mixtures containing the majority of partially O-methylated alditol acetates (PMAAs), necessary for the GC-MS based identification of glycosidic linkages in oligo- and polymeric structures were prepared. Rha, Fuc, Rib, Ara, Xyl, Man, Gal, and Glc were converted to their Me glycosides, and the products were progressively O-methylated using the Purdie reagent at 25 degrees C. Resulting PMGs were assayed by TLC and at times that were optimum for formation of mono-O-methyl derivatives and later for higher degrees of methylation; they were converted to PMAAs, in a process incorporating NaB(2)H(4) reduction. The majority of these can be used as standards for simultaneous identification of pyranosides and some furanosyl units particularly in heteropolysaccharides. The relative reactivities of OH-groups were determined by GC-MS as: Me alpha- and beta-Glcp, HO-2>HO-4>HO-3>HO-6, Me alpha- and beta-Galp, HO-3>HO-2>HO-4>HO-6, Me alpha-Manp, HO-3>HO-2>HO-4>HO-6, Me beta-Manp, HO-3>HO-4HO-6>HO-2, Me alpha-Rhap, OH-3>OH-2>OH-4; Me alphabeta-Fucp, OH-2>OH-3>OH-4, and Me alphabeta-Xylp, OH-2>OH-4>OH-3. The results differ from those obtained with Haworth, Hakomori, and Ciucanu methylation techniques, although some similarities occurred with the more rapid Kuhn method.     

The use of isochronal reference standards in phase and modulation fluorescence lifetime measurements

Errors in phase and modulation lifetime measurements observed with the only commercially available instrument are readily apparent when the Debye-Sears modulation tank is not perfectly tuned. Unfortunately, we have found that exact tuning was extremely difficult to achieve and maintain. We report that these errors could be reduced by using single-lifetime (homogeneous) reference standards whose fluorescence lifetime approximated that of the unknown sample (isochronal standards). A number of useful standards are suggested. In the proposed method, the phase shift and relative modulation of the sample emission are measured using the isochronal standard as a reference to determine the effective characteristics of the sinusoidal excitation. The importance of the improvement in accuracy accomplished by the proposed methods is illustrated by the accurate resolution of fluorescence lifetime heterogeneity for two known heterogeneous samples.