Wigner-Araki-Yanase Theorem for Continuous and Unbounded Conserved Observables.

The Wigner-Araki-Yanase (WAY) theorem states that additive conservation laws imply the commutativity of exactly implementable projective measurements and the conserved observables of the system. Known proofs of this theorem are only restricted to bounded or discrete-spectrum conserved observables of the system and are not applicable to unbounded and continuous observables like a momentum operator. In this Letter, we present the WAY theorem for possibly unbounded and continuous conserved observables under the Yanase condition, which requires that the probe positive operator-valued measure should commute with the conserved observable of the probe system. As a result of this WAY theorem, we show that exact implementations of the projective measurement of the position under momentum conservation and of the quadrature amplitude using linear optical instruments and photon counters are impossible. We also consider implementations of unitary channels under conservation laws and find that the conserved observable L_{S} of the system commutes with the implemented unitary U_{S} if L_{S} is semibounded, while U_{S}^{†}L_{S}U_{S} can shift up to possibly nonzero constant factor if the spectrum of L_{S} is upper and lower unbounded. We give simple examples of the latter case, where L_{S} is a momentum operator.

Safety assessment of L-Arg oral intake in healthy subjects: a systematic review of randomized control trials.

L-Arg is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no-observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or/one-time dose), and the treatment duration was 1-84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: - 0.02-0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose using a weighted change-point regression model (UMIN000046133).Registration and protocol: Umin.ac.jp as UMIN000046133.

A change-point regression approach for estimating no observed adverse effect level from systematic review.

Systematic reviews can be used not only to evaluate the efficacy and usefulness of a drug or food ingredient, but also as a safety assessment method. One of the aims of safety assessment is to estimate the no observed adverse effect level and the lowest observed adverse effect level. However, no methodology to statistically estimate the no observed adverse effect level from systematic review results has yet been reported. Estimation of the no observed adverse effect level involves a search for the dose above which adverse events occur is even exploration of the thresholds in dose response. To search for the dose above which adverse events occur, we examined an estimation method using the weighted change-point regression model, which includes the weights of each study used for systematic reviews in the model. This model could be applied to safety data of an omega-3 study in the form of a systematic review. We demonstrated that the dose response to omega-3 intake regarding adverse events had a threshold value and that the no observed adverse effect level could be estimated using the developed model.

Safety assessment of L-lysine oral intake: a systematic review.

Currently, the use of amino acids in supplements and functional foods is increasing globally. However, there are no guidelines for the upper limit of ingestion for the safe use of these amino acids. Safety evaluation of chemical substances is generally performed through non-clinical and clinical studies. However, amino acids that have these safety data are limited. Therefore, we used a systematic review approach for evaluating the safety of amino acids. In the present study, we evaluated the safety of L-lysine added to an ordinary diet in humans. Using PubMed, Cochrane Library, Ichushi Web, and EBSCOhost as search databases, we comprehensively searched human studies on oral ingestion of L-lysine. Ultimately, 71 studies were selected for evaluation. Of these, 12 studies were of relatively high quality with Jadad scores ≥ 3. The dose range of L-lysine in the selected studies was 16.8-17,500 mg/day, and the range of dosing period was 1-1095 days. The observed adverse events were mainly subjective symptoms related to the gastrointestinal tract such as nausea, stomachache, and diarrhea. The provisional no-observed-adverse-effect level obtained based on these gastrointestinal symptoms was 6000 mg/person/day. Integrated analysis of the risk for developing gastrointestinal symptoms revealed that the risk ratio was 1.02 (95% CI, 0.96-1.07; p = 0.49); thus, no significant increase was observed. (UMIN000028914).