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.

The decomposition of some RDX and HMX based materials in the one dimensional time to explosion apparatus. Part 2. Estimating the violence of the cook-off event

Various methods of assessment have been applied to the One Dimensional Time to Explosion (ODTX) apparatus and experiments with the aim of allowing an estimate of the comparative violence of the explosion event to be made. Non-mechanical methods used were a simple visual inspection, measuring the increase in the void volume of the anvils following an explosion and measuring the velocity of the sound produced by the explosion over 1 metre. Mechanical methods used included monitoring piezo-electric devices inserted in the frame of the machine and measuring the rotational velocity of a rotating bar placed on the top of the anvils after it had been displaced by the shock wave. This last method, which resembles original Hopkinson Bar experiments, seemed the easiest to apply and analyse, giving relative rankings of violence and the possibility of the calculation of a “detonation” pressure.

Assessing the impact of the 'Decoupling' reform of the common agricultural policy on Irish farmers' off-farm labour market participation decisions

This paper assesses the impact of the 'decoupling' reform of the Common Agricultural Policy on the labour allocation decisions of Irish farmers. The agricultural household decision-making model provides the conceptual and theoretical framework to examine the interaction between government subsidies and farmers' time allocation decisions. The relationship postulated is that 'decoupling' of agricultural support from production would probably result in a decline in the return to farm labour but it would also lead to an increase in household wealth. The effect of these factors on how farmers allocate their time is tested empirically using labour participation and labour supply models. The models developed are sufficiently general for application elsewhere. The main findings for the Irish situation are that the decoupling of direct payments is likely to increase the probability of farmers participating in the off-farm employment market and that the amount of time allocated to off-farm work will increase.

Night-time tropospheric chemistry of the unsaturated alcohols (Z)-pent-2-en-1-ol and pent-1-en-3-ol: Kinetic studies of reactions of NO3 and N2O5 with stress-induced plant emissions

The night-time tropospheric chemistry of two stress-induced volatile organic compounds (VOCs), (Z)-pent-2-en-1-ol and pent-1-en-3-ol, has been studied at room temperature. Rate coefficients for reactions of the nitrate radical (NO3) with these pentenols were measured using the discharge-flow technique. Because of the relatively low volatility of these compounds, we employed off-axis continuous-wave cavity-enhanced absorption spectroscopy for detection of NO3 in order to be able to work in pseudo first-order conditions with the pentenols in large excess over NO3. The rate coefficients were determined to be (1.53 +/- 0.23) x 10(-13) and (1.39 +/- 0.19) x 10(-14) cm(3) molecule(-1) s(-1) for reactions of NO3 with (Z)-pent-2-en-1-ol and pent-1-en-3-ol. An attempt to study the kinetics of these reactions with a relative-rate technique, using N2O5 as source of NO3 resulted in significantly higher apparent rate coefficients. Performing relative-rate experiments in known excesses of NO2 allowed us to determine the rate coefficients for the N2O5 reactions to be (5.0 +/- 2.8) x 10(-19) cm(3) molecule(-1) s(-1) for (Z)-pent-2-en-1-ol, and (9.1 +/- 5.8) x 10(-19) cm(3) molecule(-1) s(-1) for pent-1-en-3-ol. We show that these relatively slow reactions can indeed interfere with rate determinations in conventional relative-rate experiments.

Evaluation of the time resolved fluorescence immunoassay (TRFIA) for the detection of varicella zoster virus (VZV) antibodies following vaccination of healthcare workers

Determination of varicella zoster virus (VZV) immunity in healthcare workers without a history of chickenpox is important for identifying those in need of vOka vaccination. Post immunisation, healthcare workers in the UK who work with high risk patients are tested for seroconversion. To assess the performance of the time-resolved fluorescence immunoassay (TRFIA) for the detection of antibody in vaccinated as well as unvaccinated individuals, a cut-off was first calculated. VZV-IgG specific avidity and titres six weeks after the first dose of vaccine were used to identify subjects with pre-existing immunity among a cohort of 110 healthcare workers. Those with high avidity (≥60%) were considered to have previous immunity to VZV and those with low or equivocal avidity (<60%) were considered naive. The former had antibody levels ≥400mIU/mL and latter had levels <400mIU/mL. Comparison of the baseline values of the naive and immune groups allowed the estimation of a TRFIA cut-off value of >130mIU/mL which best discriminated between the two groups and this was confirmed by ROC analysis. Using this value, the sensitivity and specificity of TRFIA cut-off were 90% (95% CI 79-96), and 78% (95% CI 61-90) respectively in this population. A subset of samples tested by the gold standard Fluorescence Antibody to Membrane Antigen (FAMA) test showed 84% (54/64) agreement with TRFIA.

On variational data assimilation in continuous time

Variational data assimilation in continuous time is revisited. The central techniques applied in this paper are in part adopted from the theory of optimal nonlinear control. Alternatively, the investigated approach can be considered as a continuous time generalization of what is known as weakly constrained four-dimensional variational assimilation (4D-Var) in the geosciences. The technique allows to assimilate trajectories in the case of partial observations and in the presence of model error. Several mathematical aspects of the approach are studied. Computationally, it amounts to solving a two-point boundary value problem. For imperfect models, the trade-off between small dynamical error (i.e. the trajectory obeys the model dynamics) and small observational error (i.e. the trajectory closely follows the observations) is investigated. This trade-off turns out to be trivial if the model is perfect. However, even in this situation, allowing for minute deviations from the perfect model is shown to have positive effects, namely to regularize the problem. The presented formalism is dynamical in character. No statistical assumptions on dynamical or observational noise are imposed.

Sensitivity and out-of-sample error in continuous time data assimilation

Data assimilation refers to the problem of finding trajectories of a prescribed dynamical model in such a way that the output of the model (usually some function of the model states) follows a given time series of observations. Typically though, these two requirements cannot both be met at the same time–tracking the observations is not possible without the trajectory deviating from the proposed model equations, while adherence to the model requires deviations from the observations. Thus, data assimilation faces a trade-off. In this contribution, the sensitivity of the data assimilation with respect to perturbations in the observations is identified as the parameter which controls the trade-off. A relation between the sensitivity and the out-of-sample error is established, which allows the latter to be calculated under operational conditions. A minimum out-of-sample error is proposed as a criterion to set an appropriate sensitivity and to settle the discussed trade-off. Two approaches to data assimilation are considered, namely variational data assimilation and Newtonian nudging, also known as synchronization. Numerical examples demonstrate the feasibility of the approach.

Time-resolved gas-phase kinetic, quantum chemical, and RRKM studies of reactions of silylene with alcohols

Time-resolved kinetic studies of silylene, SiH2, generated by laser flash photolysis of 1-silacyclopent-3-ene and phenylsilane, have been carried out to obtain rate constants for its bimolecular reactions with methanol, ethanol, 1-propanol, 1-butanol and 2-methyl-1-butanol. The reactions were studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at room temperature. In the study with methanol several buffer gases were used. All five reactions showed pressure dependences characteristic of third body assisted association reactions. The rate constant pressure dependences were modelled using RRKM theory, based on Eo values of the association complexes obtained by ab initio calculation (G3 level). Transition state models were adjusted to fit experimental fall-off curves and extrapolated to obtain k∞ values in the range 1.9 to 4.5 × 10-10 cm3 molecule-1 s-1. These numbers, corresponding to the true bimolecular rate constants, indicate efficiencies of between 16 and 67% of the collision rates for these reactions. In the reaction of SiH2 + MeOH there is a small kinetic component to the rate which is second order in MeOH (at low total pressures). This suggests an additional catalysed reaction pathway, which is supported by the ab initio calculations. These calculations have been used to define specific MeOH-for-H2O substitution effects on this catalytic pathway. Where possible our experimental and theoretical results are compared with those of previous studies.

Tropical Atlantic variability modes (1979–2002). Part I: Time-evolving SST modes related to West African rainfall

This work presents a description of the 1979–2002 tropical Atlantic (TA) SST variability modes coupled to the anomalous West African (WA) rainfall during the monsoon season. The time-evolving SST patterns, with an impact on WA rainfall variability, are analyzed using a new methodology based on maximum covariance analysis. The enhanced Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) dataset, which includes measures over the ocean, gives a complete picture of the interannual WA rainfall patterns for the Sahel dry period. The leading TA SST pattern, related to the Atlantic El Niño, is coupled to anomalous precipitation over the coast of the Gulf of Guinea, which corresponds to the second WA rainfall principal component. The thermodynamics and dynamics involved in the generation, development, and damping of this mode are studied and compared with previous works. The SST mode starts at the Angola/Benguela region and is caused by alongshore wind anomalies. It then propagates westward via Rossby waves and damps because of latent heat flux anomalies and Kelvin wave eastward propagation from an off-equatorial forcing. The second SST mode includes the Mediterranean and the Atlantic Ocean, showing how the Mediterranean SST anomalies are those that are directly associated with the Sahelian rainfall. The global signature of the TA SST patterns is analyzed, adding new insights about the Pacific– Atlantic link in relation to WA rainfall during this period. Also, this global picture suggests that the Mediterranean SST anomalies are a fingerprint of large-scale forcing. This work updates the results given by other authors, whose studies are based on different datasets dating back to the 1950s, including both the wet and the dry Sahel periods.

CP-OQAM-OFDM based SC-FDMA: adjustable user bandwidth and space-time coding

The discrete Fourier transmission spread OFDM DFTS-OFDM) based single-carrier frequency division multiple access (SC-FDMA) has been widely adopted due to its lower peak-to-average power ratio (PAPR) of transmit signals compared with OFDM. However, the offset modulation, which has lower PAPR than general modulation, cannot be directly applied into the existing SC-FDMA. When pulse-shaping filters are employed to further reduce the envelope fluctuation of transmit signals of SC-FDMA, the spectral efficiency degrades as well. In order to overcome such limitations of conventional SC-FDMA, this paper for the first time investigated cyclic prefixed OQAMOFDM (CP-OQAM-OFDM) based SC-FDMA transmission with adjustable user bandwidth and space-time coding. Firstly, we propose CP-OQAM-OFDM transmission with unequally-spaced subbands. We then apply it to SC-FDMA transmission and propose a SC-FDMA scheme with the following features: a) the transmit signal of each user is offset modulated single-carrier with frequency-domain pulse-shaping; b) the bandwidth of each user is adjustable; c) the spectral efficiency does not decrease with increasing roll-off factors. To combat both inter-symbolinterference and multiple access interference in frequencyselective fading channels, a joint linear minimum mean square error frequency domain equalization using a prior information with low complexity is developed. Subsequently, we construct space-time codes for the proposed SC-FDMA. Simulation results confirm the powerfulness of the proposed CP-OQAM-OFDM scheme (i.e., effective yet with low complexity).

The transatlantic dimensions of the time lord: Doctor Who and the relationships between British and North American television

This chapter explores some of the textual specificity of the Steven Moffat/Matt Smith Doctor Who, in relation to its positioning within the current transatlantic television landscape. The chapter develops further the existing scholarship on Doctor Who, by both offering a critical assessment of the transatlantic dimensions of the Moffat/Smith-era Doctor Who, and by challenging some of the existing critical arguments about Doctor Who's transatlantic dimensions. Particular attention is paid to the casting, physicality and costuming of actor Matt Smith as the Doctor in relation to notions of Britishness.

A simple framework for assessing the trade-off between the climate impact of aviation carbon dioxide emissions and contrails for a single flight

Persistent contrails are an important climate impact of aviation which could potentially be reduced by re-routing aircraft to avoid contrailing; however this generally increases both the flight length and its corresponding CO emissions. Here, we provide a simple framework to assess the trade-off between the climate impact of CO emissions and contrails for a single flight, in terms of the absolute global warming potential and absolute global temperature potential metrics for time horizons of 20, 50 and 100 years. We use the framework to illustrate the maximum extra distance (with no altitude changes) that can be added to a flight and still reduce its overall climate impact. Small aircraft can fly up to four times further to avoid contrailing than large aircraft. The results have a strong dependence on the applied metric and time horizon. Applying a conservative estimate of the uncertainty in the contrail radiative forcing and climate efficacy leads to a factor of 20 difference in the maximum extra distance that could be flown to avoid a contrail. The impact of re-routing on other climatically-important aviation emissions could also be considered in this framework.

The impact of number mismatch and passives on the real-time processing of relative clauses

Language processing plays a crucial role in language development, providing the ability to assign structural representations to input strings (e.g., Fodor, 1998). In this paper we aim at contributing to the study of children's processing routines, examining the operations underlying the auditory processing of relative clauses in children compared to adults. English-speaking children (6–8;11) and adults participated in the study, which employed a self-paced listening task with a final comprehension question. The aim was to determine (i) the role of number agreement in object relative clauses in which the subject and object NPs differ in terms of number properties, and (ii) the role of verb morphology (active vs. passive) in subject relative clauses. Even though children's off-line accuracy was not always comparable to that of adults, analyses of reaction times results support the view that children have the same structural processing reflexes observed in adults.

The development of time-based prospective memory in childhood: the role of working memory updating

This large-scale study examined the development of time-based prospective memory (PM) across childhood and the roles that working memory updating and time monitoring play in driving age effects in PM performance. One hundred and ninety-seven children aged 5 to 14 years completed a time-based PM task where working memory updating load was manipulated within individuals using a dual task design. Results revealed age-related increases in PM performance across childhood. Working memory updating load had a negative impact on PM performance and monitoring behavior in older children, but this effect was smaller in younger children. Moreover, the frequency as well as the pattern of time monitoring predicted children’s PM performance. Our interpretation of these results is that processes involved in children’s PM may show a qualitative shift over development from simple, nonstrategic monitoring behavior to more strategic monitoring based on internal temporal models that rely specifically on working memory updating resources. We discuss this interpretation with regard to possible trade-off effects in younger children as well as alternative accounts.

Unrestricted Skyrme-tensor time-dependent Hartree-Fock model and its application to the nuclear response from spherical to triaxial nuclei

The nuclear time-dependent Hartree-Fock model formulated in three-dimensional space, based on the full standard Skyrme energy density functional complemented with the tensor force, is presented. Full self-consistency is achieved by the model. The application to the isovector giant dipole resonance is discussed in the linear limit, ranging from spherical nuclei (16O and 120Sn) to systems displaying axial or triaxial deformation (24Mg, 28Si, 178Os, 190W and 238U). Particular attention is paid to the spin-dependent terms from the central sector of the functional, recently included together with the tensor. They turn out to be capable of producing a qualitative change on the strength distribution in this channel. The effect on the deformation properties is also discussed. The quantitative effects on the linear response are small and, overall, the giant dipole energy remains unaffected. Calculations are compared to predictions from the (quasi)-particle random-phase approximation and experimental data where available, finding good agreement