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Additional file 3.

Additional file 2.

[Background] Cleft lip and palate (cleft L/P) is one of the most common congenital anomalies and its etiology is assumed to be multifactorial. Recent epidemiological data involving a small number of participants suggested an association between perinatal exposure to heavy metals and cleft L/P in affected children. However, this association requires further investigation in a large cohort. [Methods] This nested case–control study used a dataset of The Japan Environment and Children’s Study, which is an ongoing research project to investigate the association between environmental factors and mother-child health. Participants were enrolled between 2011 and 2014. From the records of fetuses/children, we extracted data of isolated cleft L/P cases and matched children without cleft L/P at a ratio of 1:10. The exposures of interest were in utero exposure to four metals (mercury [Hg], lead [Pb], cadmium [Cd], and manganese [Mn]), which were sampled from mothers in the second/third trimester. Conditional logistic regression was used to assess the association between heavy metal exposure and isolated cleft L/P. Three sensitivity analyses were conducted to test the robustness of the findings, including the change in case definition and statistical methods. [Results] Of 104, 062 fetal records involving both live-birth and stillbirth, we identified 192 children with isolated cleft L/P and 1, 920 matched controls. Overall, the blood metal levels were low (for example, median Pb level was 5.85, 6.22, and 5.75 μg/L in the total cohort, cases, and controls, respectively). Univariate and multivariate analyses showed that levels of none of the four heavy metals in the mother’s blood during pregnancy were associated with the risk of cleft L/P in offspring; the adjusted odds ratios (per 1 μg/L increase) with 95% intervals were 0.96 (0.91–1.03), 1.01 (0.94–1.08), 1.00 (0.61–1.63) and 1.00 (0.97–1.03) for Hg, Pb, Cd and Mn, respectively. The results were consistent in all sensitivity analyses. [Conclusions] Exposure to these four metals during pregnancy was not associated with isolated cleft L/P at the low exposure level in our cohort., 子どもの健康と環境に関する全国調査（エコチル調査）＜妊婦の血中重金属濃度と生まれた子どもの口唇口蓋裂との関連について --エコチル調査＞. 京都大学プレスリリース. 2022-04-12.

Additional file 1 : Table S1 List of definitions. Table S2 Comorbidities coded under the ICD10 coding system (prevalence ≥ 10%) in patients diagnosed with gout and asymptomatic hyperuricemia (n = 276)

Contact with companion animals has been suggested to have important roles in enhancing child development. However, studies focused on child development and pet ownership at a very early age are limited. The purpose of the current study was to investigate child development in relation to pet ownership at an early age in a nationwide prospective birth cohort study: the Japan Environment and Children&rsquo, s Study. Associations between cat and dog ownership at six months and infant development at 12 months of age were examined in this study. Infant development was assessed using the Ages &amp, Stages QuestionnairesTM (ASQ-3) at 12 months. Among participants of (Japan Environment and Children&rsquo, s Study) JECS, those with available data of cat and dog ownership at six months and data for the ASQ-3 at 12 months were included (n = 78,868). Having dogs showed higher percentages of pass in all five domains measured by ASQ-3 (communication, gross motor, fine motor, problem-solving, and personal-social) compared to those who did not have dogs. Significantly decreased odds ratios (ORs) of developmental delays were observed in association with having dogs in all fix domains (communication: OR = 0.73, gross motor: OR = 0.86, fine motor: OR = 0.84, problem-solving: OR = 0.90, personal-social: OR = 0.83). This study suggested that early life dog ownership may reduce the risks of child developmental delays.

This paper describes a fuzzy control system for a gas cooling plant using a special-purpose fuzzy inference accelerator. The plant described had been manually controlled for over twenty years, with several failed attempts at automation. Long time lags, constantly changing system parameters, and uneven gas flow rates are some of the problems that our control system has successfully addressed. Actual working results from the plant's one and a half years of fuzzy control are presented that demonstrate the control system's reliability.