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Congenital defects of bile acid synthesis are rare disorders that cause progressive liver dysfunction. Prolonged neonatal hyperinsulism (PNH) is a separate entity that leads to persistent hypoglycemia secondary to stress. We present a 4-month-old infant who presented with liver failure secondary to a bile acid synthesis defect. The patient’s liver failure resolved with oral cholic acid therapy. This patient also developed PNH, which slowly resolved over time. This case illustrates a possible relationship between cholestatic liver failure and PNH. This relationship may help define specific stressors that increase the likelihood of developing PNH.

We are grateful to the editor and reviewers for this opportunity to respond to the five essays reviewing two recent books comparing regulation in the US and Europe: The Politics of Precaution: Regulating Health, Safety, and Environmental Risks in Europe and the United States, and The Reality of Precaution: Comparing Risk Regulation in the United States and Europe. We agree with reviewer Maria Weimer and with David Vogel that both of these books help create a research agenda for comparative studies of regulation, including studies of relative precaution, by developing theoretical explanations and a systematic basis for collecting data to test them. We also agree with reviewer Susan Rose-Ackerman that comparative studies of regulation should examine not only relative precaution, but more broadly the interrelationships among precaution, proportionality, impact assessment, cost-benefit analysis, and other analytic frameworks – and the value choices embedded in them. We addressed those important issues in the concluding chapter of our book, but they certainly deserve additional inquiry. And we thank Fabrizio Cafaggi for his extensive review of our book in an earlier issue of this journal; there he emphasized our book’s contribution to the evolving understanding of transnational regulatory networks. Both books undertake a descriptive comparison of relative precaution in American and European regulation over the past several decades. The two books differ in their findings, and in the evidence on which those findings rest. We thank reviewers Susan RoseAckerman, Adam Burgess, and Jane K. Winn for acknowledging the strong empirical evidence of actual policymaking that is assembled in our book. We disagree, however, with the reviewers who allege that our book has somehow “missed the wood for the trees” or cast “empiricism” against “humanism”, ostensibly because Europe yearns to define its “identity” as precautionary or because European regulation “feels” more precautionary. In our view, it is a mistake to confuse rhetoric with reality, or feelings with actions, and it is an illusion to conflate political aspirations with actual policymaking. That is why we studied actual policies: to test whether they reflect the political rhetoric or not. To characterize the forest and see whether it has moved, one must examine a representative sample of the trees – which is what we have done. To compare regulatory policies, one must actually study the policies and avoid being seduced by aspirational rhetoric and symbolic politics which are not themselves evidence of real regulation. * Jonathan B. Wiener is Perkins Professor of Law at Duke Law School, Professor of Environmental Policy at the Nicholas School of the Environment, and Professor of Public Policy at the Sanford School of Public Policy, at Duke University and a University Fellow of Resources for the Future (RFF). Brendon Swedlow is an Associate Professor in the Department of Political Science, at Northern Illinois University. James K. Hammitt is Professor of Economics and Decision Sciences at the Department of Health Policy and Management, Harvard School of Public Health, and visiting professor at the Toulouse School of Economics (LERNA-INRA). Michael D. Rogers is a former member of the Bureau of European Policy Advisers, at the European Commission. Peter H. Sand is lecturer in International Environmental Law at the University of Munich.

Technology Assessment (TA) is the study and evaluation of new technologies with the objective of understanding the likely impacts (costs and benefits) of these technologies on society and the environment – with the explicit aim of improving regulatory decision making concerning these technologies. This is a prospective exercise helping to ensure that “better” regulatory decisions are made by decision makers. TA and “TA like” activities are embedded within the main EU institutions. The Commission carries out Regulatory Impact Assessments on every significant regulatory proposal. It also has at its disposal a range of advisory groups which includes the European Group on Ethics in Science and New Technologies and the Institute for Prospective Technological Studies. The European Parliament has its own TA unit – the Science and Technology Options Assessment unit. The institutions are committed to quality, transparency and effectiveness in their use of expert groups and all such assessments are published on the internet. Occasionally full citizens’ consultations are carried out but this is not a formal requirement. Recent changes in the regulatory development process have emphasised the concept of “smarter” regulations. This concept is concerned not just with prospective analyses in advance of new regulations but also with the retrospective evaluation of existing regulations asking the question“Did they meet the need that was the raison d’être for enacting the regulation under consideration.”The distinction highlighted by Churchill [2] that experts should advise but not decide is intended to ensure that regulators take account of aspects other than the expert view. Nevertheless, it is essential that expert groups have the right to introduce advice thatmight otherwise be overlooked by the regulators, as is the case in a number of expert groups in the EU institutions.

The ‘modern’ approach to risk management fails with increasing scientific uncertainty. Risk regulators have responded to this difficulty by invoking the precautionary principle (PP). Under the PP, the bridge from risk assessment to risk management involves scenarios which use retrospective analyses to decide on future actions in order to avoid prospective harm. This new approach is termed ‘post‐modern’ by some observers. In response to such ‘post‐modern’ risks, the EU incorporated the PP into its primary law in 1992 and issued an explanatory Communication on the PP in 2000. The Communication presented five criteria that should govern precautionary actions and these criteria are now reflected in secondary laws in a number of sectors. Critically, the practical application of this body of law is being clarified through the case law of the EU courts. PP case law up to the end of 2008 is critically analysed in the light of the five criteria set out in the Commission’s Communication. It is found that the first ...

The European regulation of genetically modified plants is a particular example of technological risk management that has become an essential part of the management of change. The role of regulators in this management process, when there are demands for regulatory action concerning unquantified (and sometimes unquantifiable) technological risks – with regulation under conditions of uncertainty – is explored. Where the retrospective evidence concerning a postulated risk scenario is sparse, the precautionary principle (PP) may be invoked. The origins of the European regulatory system, which applied until 17 October 2002 (Directive 90/220), why this has been revised (Directive 2001/18) and the probable impact of this revision are described. This is illustrated with risk assessments that have accompanied submissions for marketing approval for genetically modified plants under Directive 90/220. Some of the problems associated with the PP and the regulation of GM plants are discussed.

The International Glutamate Technical Committee (IGTC) wishes to comment on a recent publication in the Journal entitled “Genotoxicity of monosodium glutamate” (authored by Ataseven N, Yuzbasioglu D, Keskin AC and Unal F) (Ataseven et al. 2016). In particular, we wish to highlight that, in our considered view, the results of this study were inappropriately discussed and that references were selectively used.

The European Commission has proposed a radical new policy for the regulation of chemicals in the EU in the form of a White Paper. The current system has separate regulatory provisions for "new" chemicals (introduced to the market since September 18, 1981) and "existing" chemicals (on the market before September 18,1981). The proposed future policy will have a single unified regulatory system for all chemicals, which should result in better regulation of chemicals in the EU single market. It will be better because risk assessments will be targeted at the chemicals of greatest concern. Furthermore, the system will be streamlined, making regulatory decisions faster, and thus reducing the so-called burden of the past (the large number of chemicals that have never been assessed for their risks to human health or the environment). The new system incorporates the precautionary principle, which will be applied where there is an early indication of unacceptable risk or where there is undue delay in the regulatory process. Moreover, the new strategy is intended to promote greater transparency for all stakeholders.

The regulation of health and environmental risks has generated transatlantic contro- versy concerning precaution and the precautionary principle (PP). Conventional wisdom sees the European Union endorsing the PP and proactively regulating uncertain risks, while the United States opposes the PP and waits for evidence of harm before regu- lating. Without favouring either approach, this paper critically analyses the conventional depiction of transatlantic divergence. First, it reviews several different versions of the PP and their different implications. Second, it broadens the transatlantic comparison of precaution beyond the typical focus on single-risk examples, such as genetically modi- eed foods. Through case studies, including hormones in beef and milk production and mad cow disease in beef and in blood donations, as well as reference to a wider array of risks, the paper demonstrates that relative precaution varies enormously. Sometimes the EU is more precautionary than the US (such as regarding hormones in beef), while sometimes the US is more precautionary than the EU (such as regarding mad cow disease in blood). Thus, neither the EU nor the US can claim to be categorically 'more precautionary' than the other. The real pattern is complex and risk-speciec. Third, the paper seeks explanations for this complex pattern in eve sets of hypotheses: optimal tailoring on the merits, political systems, risk perceptions, trade protectionism, and legal systems. None of these hypotheses fully explains the observed complex pattern of rela- tive transatlantic precaution. The paper concludes that differences in relative precaution depend more on the context of the particular risk than on broad differences in national regulatory regimes.

Uncertainty, the precautionary principle and scenario are three important concepts in current regulatory debates concerned with risk management. In this paper, each concept is described in relation to its regulatory context and a linkage between the three concepts is established. Three scenarios relating to increasing scientific and technical uncertainty are presented. The most obvious regulatory approach to uncertainty is to ban a product, process or substance under the aegis of the precautionary principle. However, this may not be appropriate in all cases and a range of other possible policy responses to uncertainty are discussed and avenues for further research suggested.

Antiretroviral therapy may lead to decreased shedding of human immunodeficiency virus type 1 (HIV-1) in genital secretions. Thirty men, 19 receiving amprenavir and 11 receiving amprenavir, zidovudine, and lamivudine, donated blood and semen while undergoing treatment, to evaluate the effects of these medications on HIV-1 shedding in semen. Before therapy, 4 men had HIV-1 RNA levels in seminal plasma >6.0 log10 (1 million) copies/mL, markedly higher than levels in blood plasma. Most men (77%) had HIV-1 RNA levels in seminal plasma below the limit of quantification during therapy. Amprenavir alone suppressed HIV-1 RNA levels to

Please see related articles and author responses: http://www.nutritionandmetabolism.com/content/9/1/50http://www.nutritionandmetabolism.com/content/10/1/10http://www.nutritionandmetabolism.com/content/10/1/13 ABSTRACT: The article entitled "Monosodium glutamate (MSG) intake is associated with the prevalence of metabolic syndrome in a rural Thai population", concluded that higher amounts of individual's MSG consumption are associated with the risk of having the metabolic syndrome and being overweight independent of other major determinants. However, this epidemiological study is the only study indicating such a relationship between MSG intake and the prevalence of metabolic syndrome and there is no direct supporting evidence for a causal relationship between MSG intake and prevalence of metabolic syndrome. This study does not indicate that MSG causes metabolic syndrome. Furthermore, there are several questionable points concerning study methods. Further carefully designed studies taking into account all glutamate sources are necessary to demonstrate the relationship between overweight, metabolic syndrome, MSG intake and umami sensitivity.

A theoretical analysis of composite electrodes consisting of a mixture of an intercalation host and a solid electrolyte has suggested that the effective ionic conductivity of the latter should directly influence the apparent chemical diffusion coefficient of the electroactive species in the electrode. This investigation has measured the dependence of the apparent chemical diffusion coefficient on the particle size, electrode composition and electrode thickness of a model composite electrode consisting of niobium disulphide with a range of silver ion conducting glasses. The theoretical model is validated to a limited extent and deviations are ascribed to the predominant influence of diffusion in the host particles.

Twenty-six strains of Leishmania were isolated from cutaneous lesions in humans in 3 different geographical areas of Ecuador. The species were identified by enzyme electrophoresis as Leishmania braziliensis, L. panamensis, L. guyanensis, L. mexicana, and L. amazonensis.

Three categories of uncertainty in relation to risk assessment are defined; uncertainty in effect, uncertainty in cause, and uncertainty in the relationship between a hypothesised cause and effect. The Precautionary Principle (PP) relates to the third type of uncertainty. Three broad descriptions of the PP are set out, uncertainty justifies action, uncertainty requires action, and uncertainty requires a reversal of the burden of proof for risk assessments. The application of the PP is controversial but what matters in practise is the precautionary action (PA) that follows. The criteria by which the PAs should be judged are detailed. This framework for risk assessment and management under uncertainty is then applied to the envisaged European system for the regulation of chemicals. A new EU regulatory system has been proposed which shifts the burden of proof concerning risk assessments from the regulator to the producer, and embodies the PP in all three of its main regulatory stages. The proposals are critically discussed in relation to three chemicals, namely, atrazine (an endocrine disrupter), cadmium (toxic and possibly carcinogenic), and hydrogen fluoride (a toxic, high-production-volume chemical). Reversing the burden of proof will speed up the regulatory process but the examples demonstrate that applying the PP appropriately, and balancing the countervailing risks and the socio-economic benefits, will continue to be a difficult task for the regulator. The paper concludes with a discussion of the role of precaution in the management of change and of the importance of trust in the effective regulation of uncertain risks.

Management of antiretroviral treatment failure in patients receiving protease inhibitor (PI)-containing regimens is a therapeutic challenge.To assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen.Multicenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks.Thirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States.A total of 481 human immunodeficiency virus (HIV)-infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL.Selectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil.Primary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility.Of 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P =.002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P.001). Baseline HIV-1 hypersusceptibility to efavirenz (or = 0.4-fold difference in susceptibility compared with reference virus) was associated with suppression of viral load at 24 weeks to below 200 copies/mL (odds ratio [OR], 3.49; 95% confidence interval [CI], 1.62-7.33; P =.001), and more than 10-fold reduction in efavirenz susceptibility, with less likelihood of suppression at 24 weeks (OR, 0.28; 95% CI, 0.09-0.87; P =.03).In this study of antiretroviral-experienced patients with advanced immunodeficiency, viral load suppression to below 200 copies/mL was achieved in 31% of patients with regimens containing 4 or 5 new drugs. Use of 2 PIs, being naive to NNRTIs, and baseline hypersusceptibility to efavirenz were associated with a favorable outcome.

We measured the effect of 3 d of creatine (Cr) supplementation on repeated sprint performance and thigh muscle volume in elite power athletes.Ten male (mean +/- standard deviation of body mass and percentage of fat (81.1 +/- 10.5 kg and 9.8 +/- 3.5) and ten female (58.4 +/- 5.3 kg and 15.0 +/- 3.4) athletes were matched for sex and 10-s cycle sprint scores, paired by rank, and randomly assigned to the Cr or placebo (P) group. Subjects completed six maximal 10-s cycle sprints interspersed with 60 s of recovery before and after 3 d of Cr (0.35 g/kg of fat-free mass) or P (maltodextrin) ingestion. Before and after supplementation, 10 contiguous transaxial images of both thighs were obtained with magnetic resonance imaging.Cr supplementation resulted in statistically significant increases in body mass (0.9 +/- 0.1 kg, P0.03), total work during the first sprint (P0.04), and peak power during sprints 2 to 6 (P0.10). As expected, total work and peak power values for males were greater than those for their female counterparts during the initial sprint (P0.02); however, the reverse was true during the last three sprints (P0.01). Imaging data showed a 6.6% increase in thigh volume in five of six Cr subjects (P = 0.05).These data indicate that 3 d of Cr supplementation can increase thigh muscle volume and may enhance cycle sprint performance in elite power athletes; moreover, this effect is greater in females as sprints are repeated.

ContextManagement of antiretroviral treatment failure in patients receiving protease inhibitor (PI)–containing regimens is a therapeutic challenge.ObjectiveTo assess whether adding a second PI improves antiviral efficacy of a 4-drug combination in patients with virologic failure while taking a PI-containing regimen.DesignMulticenter, randomized, 4-arm trial, double-blind and placebo-controlled for second PI, conducted between October 1998 and April 2000, for which there was a 24-week primary analysis with extension to 48 weeks.SettingThirty-one participating AIDS (acquired immunodeficiency syndrome) Clinical Trials Units in the United States.ParticipantsA total of 481 human immunodeficiency virus (HIV)–infected persons with prior exposure to a maximum of 3 PIs and viral load above 1000 copies/mL.InterventionSelectively randomized assignment (per prior PI exposure) to saquinavir (n = 116); indinavir (n = 69); nelfinavir (n = 139); or placebo twice per day (n = 157); in combination with amprenavir, abacavir, efavirenz, and adefovir dipivoxil.Main Outcome MeasuresPrimary efficacy analysis involved the proportion with viral load below 200 copies/mL at 24 weeks. Other measures were changes in viral load and CD4 cell count from baseline, adverse events, and HIV drug susceptibility.ResultsOf 481 patients, 148 (31%) had a viral load below 200 copies/mL at week 24. The proportions of patients with a viral load below 200 copies/mL in the saquinavir, indinavir, nelfinavir, and placebo arms were 34% (40/116), 36% (25/69), 34% (47/139), and 23% (36/157), respectively. The proportion in the combined dual-PI arms was higher than in the amprenavir-plus-placebo arm (35% [112/324] vs 23% [36/157], respectively; P = .002). Overall, a higher proportion of nonnucleoside reverse transcriptase inhibitor (NNRTI)–naive patients had a viral load below 200 copies/mL compared with NNRTI-experienced patients (43% [115/270] vs 16% [33/211], respectively; P

Foreword - Notes on the Contributors - PART 1: INTERNATIONAL PERSPECTIVES - The Greening of American Industry R.D.Shelton - The Greening of Japanese Industry H.Nishimura - The Greening of European Industry R.Bryssinck - PART 2: ENVIRONMENTAL MANAGEMENT - Environmental Management: Issues and Approaches for an Organisation A.Krol - Environmental Management In an Industrial Group J.L.Mata - PART 3: TECHNOLOGY - Best Available Technology A.Fulton - The Technology of Industrial Waste Management D.Blane - PART 4: A CASE STUDY: FLUE GAS DESULPHURISATION - The Ispra Flue Gas Desulphurisation Process: Research, Development and Marketing Aspects D.van Velzen - The Chiyoda Flue Gas Desulphurisation Process (Thoroughbred): Research, Development and Commercialisation H.Yanagioka - PART 5: TOWARDS SUSTAINABILITY - Profit from Cleaner Production N.Johnston - High Tech Methodology for Residual Water E.Hermana - The Environment and the Automobile Industry: The Clean Car for Tomorrow A.Guimier - Industry and Ecology In the Context of Sustainable Development H.Furstenwerth - PART 6: THE ROLE OF FINANCIAL INSTITUTIONS - The Role of Financial Institutions: Encouraging Improved Environmental Performance H.J.Thompson - The Role of Financial Institutions: Specific Actions Developed by BEX J.Ibarrola - PART 7: THE ROLE OF THE REGULATORS - Market Based Instruments H.Landis Gabel - The Emerging Regulatory Pattern H.Jankowski - The Greening of Industry: Changing Attitudes: The Industrial Policy Point of View I.Baschab - Index

A theoretical analysis of the behaviour of a composite electrode consisting of a solid electrolyte and an insertion electrode material has suggested that the apparent chemical diffusion coefficient of the insertion metal should vary directly with the effective ionic conductivity of the composite. This effect has been studied using composites of NbS 2 and a range of silver-ion-conducting glasses. The very small dependence on conductivity found for this system is tentatively ascribed to a non-equilibrium intercalation which varies with depth in the composite region for low conductance glasses.

A statistical computer model of mixed phase electrode systems has been reformulated to extend its applicability to include standard percolation conditions, and the effects of changing composition and lattice dimensions have been investigated. When both phases are present at volume percentages above a certain critical value, the effective interfacial area of the mixed phase region can be raised indefinitely by increasing the thickness of the region. Below this limit a steady reduction in the ‘efficiency’ of the mixed phase region, rather than the abrupt cut-off suggested by percolation theory, is predicted.

Eighteen patients received 1,250 mg of allopurinol riboside (AR) four times daily for 28 d. Nine of the patients concurrently received 500 mg probenecid (PB) four times daily. Cure was assessed clinically and parasitologically. Patients who had culture-positive and nonhealing lesions 3 mo after therapy received pentavalent antimony. Of the nine patients who received AR alone, four (44%) had clinical improvement at the end of therapy and two (22%) were culture-negative. A third patient became culture negative at 2 mo after therapy. The culture-negative patients were completely healed at 1 mo and remained so at 1 y after therapy. Of the nine patients who received AR plus PB, four had complete healing and two had clinical improvement at the end of therapy; however, all patients remained culture-positive. At 2-3 mo after therapy, six (67%) of the patients were completely healed, and of these, five (56%) were culture-negative. The drug was well-tolerated.

A general synthesis of a number of diethyl coumarin-3-phosphonates (3) has been achieved using titanium tetrachloride-pyridine as the condensing agent.