New scientific paradigms for probiotics and prebiotics

The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics. Humans have evolved in symbiosis with an estimated 1014 resident microorganisms. However, as medicine has widely defined and explored the perpetrators of disease, including those of microbial origin, it has paid relatively little attention to the microbial cells that constitute the most abundant life forms associated with our body. Microbial metabolism in humans and animals constitutes an intense biochemical activity in the body, with profound repercussions for health and disease. As understanding of the human genome constantly expands, an important opportunity will arise to better determine the relationship between microbial populations within the body and host factors (including gender, genetic background, and nutrition) and the concomitant implications for health and improved quality of life. Combined human and microbial genetic studies will determine how such interactions can affect human health and longevity, which communication systems are used, and how they can be influenced to benefit the host. Probiotics are defined as live microorganisms which, when administered in adequate amounts confer a health benefit on the host.1 The probiotic concept dates back over 100 years, but only in recent times have the scientific knowledge and tools become available to properly evaluate their effects on normal health and well being, and their potential in preventing and treating disease. A similar situation exists for prebiotics, defined by this group as non-digestible substances that provide a beneficial physiological effect on the host by selectively stimulating the favorable growth or activity of a limited number of indigenous bacteria. Prebiotics function complementary to, and possibly synergistically with, probiotics. Numerous studies are providing insights into the growth and metabolic influence of these microbial nutrients on health. Today, the science behind the function of probiotics and prebiotics still requires more stringent deciphering both scientifically and mechanistically. The explosion of publications and interest in probiotics and prebiotics has resulted in a body of collective research that points toward great promise. However, this research is spread among such a diversity of organisms, delivery vehicles (foods, pills, and supplements), and potential health targets such that general conclusions cannot easily be made. Nevertheless, this situation is rapidly changing on a number of important fronts. With progress over the past decade on the genetics of lactic acid bacteria and the recent, 2,3 and pending, 4 release of complete genome sequences for major probiotic species, the field is now armed with detailed information and sophisticated microbiological and bioinformatic tools. Similarly, advances in biotechnology could yield new probiotics and prebiotics designed for enhanced or expanded functionality. The incorporation of genetic tools within a multidisciplinary scientific platform is expected to reveal the contributions of commensals, probiotics, and prebiotics to general health and well being and explicitly identify the mechanisms and corresponding host responses that provide the basis for their positive roles and associated claims. In terms of human suffering, the need for effective new approaches to prevent and treat disease is paramount. The need exists not only to alleviate the significant mortality and morbidity caused by intestinal diseases worldwide (especially diarrheal diseases in children), but also for infections at non-intestinal sites. This is especially worthy of pursuit in developing nations where mortality is too often the outcome of food and water borne infection. Inasmuch as probiotics and prebiotics are able to influence the populations or activities of commensal microflora, there is evidence that they can also play a role in mitigating some diseases. 5,6 Preliminary support that probiotics and prebiotics may be useful as intervention in conditions including inflammatory bowel disease, irritable bowel syndrome, allergy, cancer (especially colorectal cancer of which 75% are associated with diet), vaginal and urinary tract infections in women, kidney stone disease, mineral absorption, and infections caused by Helicobacter pylori is emerging. Some metabolites of microbes in the gut may also impact systemic conditions ranging from coronary heart disease to cognitive function, suggesting the possibility that exogenously applied microbes in the form of probiotics, or alteration of gut microecology with prebiotics, may be useful interventions even in these apparently disparate conditions. Beyond these direct intervention targets, probiotic cultures can also serve in expanded roles as live vehicles to deliver biologic agents (vaccines, enzymes, and proteins) to targeted locations within the body. The economic impact of these disease conditions in terms of diagnosis, treatment, doctor and hospital visits, and time off work exceeds several hundred billion dollars. The quality of life impact is also of major concern. Probiotics and prebiotics offer plausible opportunities to reduce the morbidity associated with these conditions. The following addresses issues that emerged from 8 workshops (Definitions, Intestinal Flora, Extra-Intestinal Sites, Immune Function, Intestinal Disease, Cancer, Genomics, and Second Generation Prebiotics), reflecting the current scientific state of probiotics and prebiotics. This is not a comprehensive review, however the study emphasizes pivotal knowledge gaps, and recommendations are made as to the underlying scientific and multidisciplinary studies that will be required to advance our understanding of the roles and impact of prebiotics, probiotics, and the commensal microflora upon health and disease management.

Investigations on the effect of amino acids on acrylamide, pyrazines, and Michael addition products in model systems

Acrylamide and pyrazine formation, as influenced by the incorporation of different amino acids, was investigated in sealed low-moisture asparagine-glucose model systems. Added amino acids, with the exception of glycine and cysteine and at an equimolar concentration to asparagine, increased the rate of acrylamide formation. The strong correlation between the unsubstituted pyrazine and acrylamide suggests the promotion of the formation of Maillard reaction intermediates, and in particular glyoxal, as the determining mode of-action. At increased amino acid concentrations, diverse effects were observed. The initial rates of acrylamide formation remained high for valine, alanine, phenylalanine, tryptophan, glutamine, and Ieucine, while a significant mitigating effect, as evident from the acrylamide yields after 60 min of heating at 160 degrees C, was observed for proline, tryptophan, glycine, and cysteine. The secondary amine containing amino acids, proline and tryptophan, had the most profound mitigating effect on acrylamide after 60 min of heating. The relative importance of the competing effect of added amino acids for alpha-dicarbonyls and acrylamide-amino, acid alkylation reactions is discussed and accompanied by data on the relative formation rates of selected amino acid-AA adducts.

Measurement of acrylamide and its precursors in potato, wheat, and rye model systems

The relationship between acrylamide and its precursors, namely, free asparagine and reducing sugars, was studied in cakes made from potato flake, wholemeal wheat, and wholemeal rye, cooked at 180 degreesC, from 5 to 60 min. Between 5 and 20 min, major losses of asparagine, water, and total reducing sugars were accompanied by large increases in acrylamide, which maximized in all three products between 25 and 30 min, followed by a slow linear reduction. Acrylamide formation did not occur to a large degree until the moisture contents of the cakes fell below 5%. Linear relationships were observed for acrylamide formation with the residual levels of asparagine and reducing sugars for all three food materials.

Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise

Recent brain imaging studies using functional magnetic resonance imaging (fMRI) have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices) during meditation (versus rest). During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ), and right posterior superior temporal sulcus (pSTS) in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in response to emotional stimuli.

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

Background: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. Method: 2 7 children who had a sibling with AS were administered the children's version of the 'Eyes Test'(Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. Results: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. Discussion: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

Design of a minimum variance multiple input-multiple output neuro self-tuning proportional-integral-derivative controller for non-linear dynamic systems

In this study a minimum variance neuro self-tuning proportional-integral-derivative (PID) controller is designed for complex multiple input-multiple output (MIMO) dynamic systems. An approximation model is constructed, which consists of two functional blocks. The first block uses a linear submodel to approximate dominant system dynamics around a selected number of operating points. The second block is used as an error agent, implemented by a neural network, to accommodate the inaccuracy possibly introduced by the linear submodel approximation, various complexities/uncertainties, and complicated coupling effects frequently exhibited in non-linear MIMO dynamic systems. With the proposed model structure, controller design of an MIMO plant with n inputs and n outputs could be, for example, decomposed into n independent single input-single output (SISO) subsystem designs. The effectiveness of the controller design procedure is initially verified through simulations of industrial examples.

Modelling complex systems for project planning - A semiotics motivated method

A large and complex IT project may involve multiple organizations and be constrained within a temporal period. An organization is a system comprising of people, activities, processes, information, resources and goals. Understanding and modelling such a project and its interrelationship with relevant organizations are essential for organizational project planning. This paper introduces the problem articulation method (PAM) as a semiotic method for organizational infrastructure modelling. PAM offers a suite of techniques, which enables the articulation of the business, technical and organizational requirements, delivering an infrastructural framework to support the organization. It works by eliciting and formalizing (e. g. processes, activities, relationships, responsibilities, communications, resources, agents, dependencies and constraints) and mapping these abstractions to represent the manifestation of the "actual" organization. Many analysts forgo organizational modelling methods and use localized ad hoc and point solutions, but this is not amenable for organizational infrastructures modelling. A case study of the infrared atmospheric sounding interferometer (IASI) will be used to demonstrate the applicability of PAM, and to examine its relevancy and significance in dealing with the innovation and changes in the organizations.

The application of implant technology for cybernetic systems

Objective: To assess the usefulness, compatibility, and long-term operability of a microelectrode array into the median nerve of the left arm of a healthy volunteer, including perception of feedback stimulation and operation of an instrumented prosthetic hand. Setting: The study was carried out from March 14 through June 18, 2002, in England and the United States. Results: The blindfolded subject received feedback information, obtained from force and slip sensors on the prosthetic hand, and subsequently used the implanted device to control the hand by applying an appropriate force to g rip an unseen object. Operability was also demonstrated remotely via the Internet, with the subject in New York, NY, and the prosthetic hand in Reading, England. Finally, the subject was able to control an electric wheelchair, via decoded signals from the implant device, to select the direction of travel by opening and closing his hand. The implantation did not result in infection or any perceivable loss of hand sensation or motion control. The implant was finally extracted because of mechanical fatigue of the percutaneous connection. Further testing after extraction has not indicated any measurable long-term defects in the subject. Conclusions: This implant may allow recipients to have abilities they would otherwise not possess. The response to stimulation improved considerably during the trial, suggesting that the subject learned to process the incoming information more effectively.

A comparison of stratosphere-troposphere transport in convection-permitting and convection-parameterizing simulations of three mesoscale convective systems

The transport of stratospheric air into the troposphere within deep convection was investigated using the Met Office Unified Model version 6.1. Three cases were simulated in which convective systems formed over the UK in the summer of 2005. For each of these three cases, simulations were performed on a grid having 4 km horizontal grid spacing in which the convection was parameterized and on a grid having 1 km horizontal grid spacing, which permitted explicit representation of the largest energy-containing scales of deep convection. Cross-tropopause transport was diagnosed using passive tracers that were initialized above the dynamically defined tropopause (2 potential vorticity unit surface) with a mixing ratio of 1. Although the synoptic-scale environment and triggering mechanisms varied between the cases, the total simulated transport was similar in all three cases. The total stratosphere-to-troposphere transport over the lifetime of the convective systems ranged from 25 to 100 kg/m2 across the simulated convective systems and resolutions, which corresponds to ∼5–20% of the total mass located within a stratospheric column extending 2 km above the tropopause. In all simulations, the transport into the lower troposphere (defined as below 3.5 km elevation) accounted for ∼1% of the total transport across the tropopause. In the 4 km runs most of the transport was due to parameterized convection, whereas in the 1 km runs the transport was due to explicitly resolved convection. The largest difference between the simulations with different resolutions occurred in the one case of midlevel convection considered, in which the total transport in the 1 km grid spacing simulation with explicit convection was 4 times that in the 4 km grid spacing simulation with parameterized convection. Although the total cross-tropopause transport was similar, stratospheric tracer was deposited more deeply to near-surface elevations in the convection-parameterizing simulations than in convection-permitting simulations.

Validation of short tandem repeat analysis for the investigation of cases of disputed paternity

This study details validation of two separate multiplex STR systems for use in paternity investigations. These are the Second Generation Multiplex (SGM) developed by the UK Forensic Science Service and the PowerPlex 1 multiplex commercially available from Promega Inc. (Madison, WI, USA). These multiplexes contain 12 different STR systems (two are duplicated in the two systems). Population databases from Caucasian, Asian and Afro-Caribbean populations have been compiled for all loci. In all but two of the 36 STR/ethnic group combinations, no evidence was obtained to indicate inconsistency with Hardy-Weinberg (HW) proportions. Empirical and theoretical approaches have been taken to validate these systems for paternity testing. Samples from 121 cases of disputed paternity were analysed using established Single Locus Probe (SLP) tests currently in use, and also using the two multiplex STR systems. Results of all three test systems were compared and no non-conformities in the conclusions were observed, although four examples of apparent germ line mutations in the STR systems were identified. The data was analysed to give information on expected paternity indices and exclusion rates for these STR systems. The 12 systems combined comprise a highly discriminating test suitable for paternity testing. 99.96% of non-fathers are excluded from paternity on two or more STR systems. Where no exclusion is found, Paternity Index (PI) values of > 10,000 are expected in > 96% of cases.

Can social interaction skills be taught by a social agent? The role of a robotic mediator in autism therapy

Increasingly socially intelligent agents (software or robotic) are used in education, rehabilitation and therapy. This paper discusses the role of interactive, mobile robots as social mediators in the particular domain of autism therapy. This research is part of the project AURORA that studies how mobile robots can be used to teach children with autism basic interaction skills that are important in social interactions among humans. Results from a particular series of trials involving pairs of two children and a mobile robot are described. The results show that the scenario with pairs of children and a robot creates a very interesting social context which gives rise to a variety of different social and non-social interaction patterns, demonstrating the specific problems but also abilities of children with autism in social interactions. Future work will include a closer analysis of interactional structure in human-human and robot-human interaction. We outline a particular framework that we are investigating.

Modelling and control of Hammerstein system using B-spline approximation and the inverse of De Boor algorithm

In this article a simple and effective controller design is introduced for the Hammerstein systems that are identified based on observational input/output data. The nonlinear static function in the Hammerstein system is modelled using a B-spline neural network. The controller is composed by computing the inverse of the B-spline approximated nonlinear static function, and a linear pole assignment controller. The contribution of this article is the inverse of De Boor algorithm that computes the inverse efficiently. Mathematical analysis is provided to prove the convergence of the proposed algorithm. Numerical examples are utilised to demonstrate the efficacy of the proposed approach.

An analytical framework for appraising Integrated Arable Farming Systems

Integrated Arable Farming Systems are examined from the perspective of the farmer considering the use of such techniques, and data are presented which suggest that the uptake of the approach may expose the manager to a greater degree of risk. Observations are made about the possible uptake of such systems in the UK and the implications this may have for agricultural and environmental policy in general.

The economic theory of international supply chains: a systems view

This paper offers an integrated analysis of out-sourcing, off-shoring and foreign direct investment within a systems view of international business. This view takes the supply chain rather than the firm as the basic unit of analysis. It argues that competition in the global economy selects supply chains that maximise the joint profit of all the firms in the chain. The systems view is compared with the firm-centred view commonly used in strategy literature. The paper shows that a firm’s strategy must be embedded within an efficient supply chain strategy, and that this strategy must be negotiated with, rather than imposed upon, other firms. The paper analyses the conditions under which various supply chain strategies - and by implication various firm-level strategies - are efficient. Only by adopting a systems view of supply chains is it possible to determine which firm-level strategies will succeed in a volatile global economy.

The kinetics of thermal generation of flavour

Control and optimization of flavor is the ultimate challenge for the food and flavor industry. The major route to flavor formation during thermal processing is the Maillard reaction, which is a complex cascade of interdependent reactions initiated by the reaction between a reducing sugar and an amino compd. The complexity of the reaction means that researchers turn to kinetic modeling in order to understand the control points of the reaction and to manipulate the flavor profile. Studies of the kinetics of flavor formation have developed over the past 30 years from single- response empirical models of binary aq. systems to sophisticated multi-response models in food matrixes, based on the underlying chem., with the power to predict the formation of some key aroma compds. This paper discusses in detail the development of kinetic models of thermal generation of flavor and looks at the challenges involved in predicting flavor.