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To gain insight into complex ion–molecule reactions induced by MeV-energy heavy ion irradiation of condensed matter, we performed a mass spectrometric study of secondary ions emitted from methanol microdroplet surfaces by 2.0 MeV C²⁺. We observed positive and negative secondary ions, including fragments, clusters, and reaction products. We found that a wider variety of negative ions than positive ions (such as C₂H⁻, C₂HO⁻, C₂H₅O⁻, and C₂H₃O₂⁻) were formed. We performed measurements for deuterated methanol (CH₃OD) droplets to identify the hydrogen elimination site of the intermediates involved in the reactions and to reveal the mechanism that generates various negative reaction product ions. Comparing the results of CH₃OD with CH₃OH droplets, we propose that the primary formation mechanism is association reactions of anion and neutral fragments, such as CH₃O⁻ + CO → C₂H₃O₂⁻. Quantum chemical calculations confirmed that the reactions can proceed with no barrier. This study provides new insights into the importance of rapid anion–molecule reactions among fragments as the mechanism that generates complex molecular species in fast heavy-ion-induced reactions.

Tetsu Tomita, Yui Sakamoto, Manabu Saito, Kojiro Hashimoto, Yasuki Ono, Kazuhiko Nakamura Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, JapanCorrespondence: Tetsu Tomita, Tel +81-172 39 5066, Fax +81-172 39 5067, Email ttomita1984@yahoo.co.jpBackground: We observed two cases of patients with schizophrenia who were treated with clozapine (250mg/day and 275mg/day, respectively) and showed neutropenia after receiving a COVID-19 vaccine (BNT162b2).Case Presentation: Case 1 is a twenty-two year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2017 and had been taking clozapine for 4 years. She received two doses of a COVID-19 vaccine and developed neutropenia (1850/mm3 (37.9% of white blood cell 4880/mm3)) 6 days after the second vaccination, but her neutropenia self-resolved naturally. Case 2 is a twenty year old woman with a diagnosis of schizophrenia. She enrolled in Clozaril® Patient Monitoring Service in 2020 and had been taking clozapine for 10 months. She received two doses of a COVID-19 vaccine and white blood cell and neutrocyte counts were below (3730/mm3 and 1440/mm3 (38.6%), respectively) the lower limits 3 days after the second vaccination. She had to discontinue clozapine according to the withdrawal definition (her neutrocyte count was < 1500/mm3), and her neutropenia self-resolved naturally.Conclusion: Physicians need to have a strict follow-up protocol in place for patients after vaccination for COVID-19.Keywords: clozapine, COVID-19, vaccine, neutropenia

In recent years, it has been reported that the prevalence of autism spectrum disorder (ASD) is increasing, but there are few research reports in Asia equivalent to those in Europe and the United States. Since large-scale epidemiological studies of neurodevelopmental disorders (NDDs) have not been conducted in Japan, the delay in early detection is conspicuous compared to other countries. Therefore, we started epidemiological studies in a medium-sized city (Hirosaki City) in northern Japan from 2013 to elucidate the prevalence of ASD and have been conducting a 9-year community cohort survey. In 2020, we published an adjusted prevalence of ASD of 3.2% at the age of 5 years, no change in 4-year incidence, and comorbidity of ASD. Since then, we have focused on sleep problems at the age of 5 years and have been studying the estimation of the prevalence of sleep disorders and the relationship with neurological development disorders. In this chapter, in addition to our research results since 2013, we will introduce the screening and support system in the community in Japan.

Supplemental Digital Content is available in the text., Objective Although autism spectrum disorder (ASD) occurs worldwide, most genomic studies on ASD were performed on those of Western ancestry. We hypothesized ASD-related copy number variations (CNVs) of Japanese individuals might be different from those of Western individuals. Methods Subjects were recruited from the Hirosaki 5-year-old children’s developmental health check-up (HFC) between 2013 and 2016 (ASD group; n = 68, control group; n = 124). This study conducted CNV analysis using genomic DNA from peripheral blood of 5-year-old Japanese children. Fisher’s exact test was applied for profiling subjects and CNV loci. Results Four ASD-related CNVs: deletion at 12p11.1, duplications at 4q13.2, 8p23.1 and 18q12.3 were detected (P = 0.015, 0.024, 0.009, 0.004, respectively). Specifically, the odds ratio of duplication at 18q12.3 was highest among the 4 CNVs (odds ratio, 8.13). Conclusions Four CNVs: microdeletion at 12p11.1, microduplications at 4q13.2, 8p23.1 and 18q12.3 were detected as ASD-related CNVs in Japanese children in this study. Although these CNVs were consistent with several reports by Western countries at cytoband levels, these did not consistent at detailed genomic positions and sizes. Our data indicate the possibility that these CNVs are characteristic of Japanese children with ASD. We conclude that Japanese individuals with ASD may harbor CNVs different from those of Western individuals with ASD.

Although research has demonstrated associations between motor coordination difficulties and psychological problems in school-age children, including emotional and behavioral problems, longitudinal changes in these problems in children with motor coordination difficulties are not fully understood.The current study aimed to identify patterns in the trajectory of emotional and behavioral problems in school-age children with motor coordination difficulties, and to elucidate the effect of co-existing neurodevelopmental traits on the occurrence and course of these problems.Using the Developmental Coordination Disorder Questionnaire, 773 children were defined as cases with motor coordination difficulties and followed for 4 years, from 6 to 10 years of age. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire completed by children's parents or guardians.We identified four trajectory patterns of emotional and behavioral problems. Children with higher autism spectrum disorder and attention deficit hyperactivity disorder traits were more likely to be assigned to poor prognostic trajectory patterns.Our findings emphasize the importance of assessing emotional and behavioral problems and co-existing neurodevelopmental traits in children with motor coordination difficulties in early elementary school.

ImportanceHeterogeneous mental health outcomes during the COVID-19 pandemic are recognized in the general population, but it has not been systematically assessed in youth with neurodevelopmental disorders (NDD), including autism spectrum (ASD).ObjectiveIdentify subgroups of youth with ASD/NDD based on the pandemic impact on symptoms and service changes, as well as predictors of outcomes.Design, Setting, and ParticipantsThis is a naturalistic observational study conducted across 14 North American and European clinical and/or research sites. Parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) adapted for Autism and Related Neurodevelopmental Conditions (AFAR) were cross-sectionally collected from April to October 2020. The sample included 1275, 5-21 year-old youth with ASD and/or NDD who were clinically well-characterized prior to the pandemic.Main Outcomes and MeasuresTo identify impact subgroups, hierarchical clustering analyzed eleven AFAR factors measuring pre- to pandemic changes in clinically relevant symptoms and service access. Random forest classification assessed the relative contribution in predicting subgroup membership of 20 features including socio-demographics, pre-pandemic service, and clinical severity along with indices of COVID-19 related experiences and environments empirically-derived from AFAR parent responses and global open sources.ResultsClustering analyses revealed four ASD/NDD impact subgroups. One subgroup - broad symptom worsening only (20% of the aggregate sample) - included youth with worsening symptoms that were above and beyond that of their ASD/NDD peers and with similar service disruptions as those in the aggregate average. The three other subgroups showed symptom changes similar to the aggregate average but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Pre-pandemic factors (e.g., number of services), pandemic environments and experiences (e.g., COVID-19 cases, related restrictions, COVID-19 Worries), and age emerged in unique combinations as distinct protective or risk factors for each subgroup. Together they highlighted the role of universal risk factors, such as risk perception, and the protective role of services before and during the pandemic, in middle childhood.Conclusions and RelevanceConcomitant assessment of changes in both symptoms and services access is critical to understand heterogeneous impact of the pandemic on ASD/NDD youth. It enabled the delineation of pathways to risk and resilience that include universal and ASD/NDD specific contributors.

We report first experimental results on the orientation effect of fast diatomic molecular projectiles on secondary ion emission processes for 3.6-MeV C2+ traversing a self-supporting target of phenylalanine (Phe) film evaporated on a carbon foil. Coincidence measurements were performed on the image of fragments resulting from the Coulomb explosion of C2+ projectiles and the time-of-flight mass spectrometry of secondary ions emitted from the Phe film. We compared the secondary ion yield for C2+ projectiles with parallel and perpendicular orientations to the beam direction. The parallel orientation was found to enhance the secondary ion yield by a factor of approximately 1.1 compared with that for the perpendicular orientation. This enhancement corresponds to an increase in the average charge of Coulomb-exploded fragments. This finding implies that there is a linear correlation between the electronic energy deposition causing secondary ion production and the effective charge number of the incident molecular ions which interact with biomolecular targets.

The aims of this study were to identify sensory processing profiles specific to preschoolers with DCD in a community sample and examine the association of sensory processing problems with motor coordination difficulties in these children. Sixty-three 5-year-old children with DCD and without other neurodevelopmental disorders and 106 age-matched typically developing children participated in this study. Sensory processing problems were assessed using the Sensory Profile. Our results demonstrated problems in wide sensory processing patterns (low registration, sensitivity and avoiding) and areas (auditory, vestibular, touch and oral) in children with DCD compared with typically developing children. Additionally, the association of problems in sensory processing patterns (sensitivity and avoiding) and areas (touch and auditory) with motor coordination difficulties were identified in children with DCD alone. Our findings indicate that sensory processing abnormalities may contribute to the pathophysiology of DCD, suggesting the importance of assessing sensory processing functions in children with DCD. Electronic supplementary material The online version of this article (10.1007/s10578-020-01013-5) contains supplementary material, which is available to authorized users.

The central symptom of autism spectrum disorder (ASD) is deficiency in social communication, which is generally viewed as being caused by pragmatic impairment (PI). PI is difficulty in using language appropriately in social situations. Studies have confirmed that PI is the result of neurological, cognitive, linguistic, and sensorimotor dysfunctions involving intricately intertwined factors. To elucidate the whole picture of this impairment, an approach from a multifaceted perspective fusing those factors is necessary. To this end, comprehensive PI mapping is a must, since no comprehensive mapping has yet been developed. The aim of this research is to present a model of annotation scheme development and corpus construction to efficiently visualize and quantify for statistical investigation occurrences of PI, which enables comprehensive mapping of PI in the spoken language of Japanese ASD individuals. We constructed system networks (lexicogrammatical option systems speakers make choices from) in the theoretical framework of Systemic Functional Linguistics, from which we developed an annotation scheme to comprehensively cover PI. Since system network covers all possible lexicogrammatical choices in linguistic interaction, it enables a comprehensive view of where and in what lexicogrammar PI occurs. Based on this annotation scheme, we successfully developed the Corpus of ASD + Typically Developed Spoken Language consisting of texts from 1,187 audiotaped tasks performed by 186 ASD and 106 typically developed subjects, accommodating approximately 1.07 million morphemes. Moreover, we were successful in the automatization of the annotation process by machine learning, accomplishing a 90 percent precision rate. We exemplified the mapping procedure with a focus on the spoken use of negotiating particles. Our model corpus is applicable to any language by incorporating our method of constructing the annotation scheme, and would give impetus to defining PI from a cross-linguistic point of view, which is needed because PI of ASD reflects cross-linguistic differences.

We present experimental results that show the secondary-ion yield depends on the structure and orientation of incident cluster ions. A beam of carbon-cluster ions ${{\mathrm{C}}_{n}}^{+}$ ($n\ensuremath{\le}4$) with an energy of 0.9 MeV per atom, which were obtained from a tandem electrostatic accelerator, was incident on a glycine target deposited on a carbon foil. The structure and orientation of the cluster ions after passing through the target were determined by the Coulomb explosion imaging method, and the positive secondary ions were simultaneously measured by time-of-flight mass spectrometry. When looking at the orientation dependence of linear structured ${{\mathrm{C}}_{2}}^{+}, {{\mathrm{C}}_{3}}^{+}$, and ${{\mathrm{C}}_{4}}^{+}$ projectiles, parallel orientations with respect to the beam direction were found to enhance the secondary-ion yield compared with perpendicular orientations. Additionally, comparison of the structure dependence of ${{\mathrm{C}}_{3}}^{+}$ and ${{\mathrm{C}}_{4}}^{+}$ projectiles with linear and ring structures showed that the secondary-ion yield was larger for linear structures. Interestingly, there was a clear correlation between the secondary-ion yield and the deposited energy density in the cluster-ion track. The energy density was calculated with electronic stopping power for incident cluster ions using linear-response dielectric theory and the cross section of the track of the incident cluster considering its geometrical structure and orientation. These results suggest that the deposited energy density in the cluster-ion track is a key parameter in the secondary-ion emission process induced by swift cluster-ion impacts.

Special Issue: Proceedings of the 19th International Conference on the Physics of Highly Charged Ions (HCI 2018), Caparica, Lisboa, Portugal, 3‐7 September 2018

Objectives: Sleep disturbances are often associated with emotional/behavioral problems in young children, but whether the association differs among Asian countries remains unknown. This study aimed to investigate the association between sleep disturbances and emotional/behavioral problems in Chinese and Japanese preschoolers and to explore potential differences.Methods: Participants were 1,020 Chinese preschoolers from 10 cities and 438 Japanese preschoolers from 1 city aged 4 to 5 years. Parents filled out the Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ).Results: Chinese children with sleep disturbances (defined as total CSHQ score >41) demonstrated more peer problems than children without, while there was no such difference in Japanese preschoolers. Domains of sleep disturbances associated with emotional/behavioral problems in Chinese children were sleep disordered breathing and daytime sleepiness, yet in Japanese children were sleep anxiety and night wakings. Children with a higher score of sleep anxiety showed more emotional problems in Japan, but fewer conduct problems in China.Conclusions: Sleep disturbances were associated with emotional/behavioral problems in preschoolers with differences between China and Japan, indicating subcultural differences in preschoolers' sleep within Asian countries.Abbreviations: CSHQ: Children's Sleep Habits Questionnaire; SDQ: Strengths and Difficulties Questionnaire; ANCOVA: analysis of covariance; SD: standard deviation; CI: confidence interval.

A time-of-flight elastic recoil detection analysis measurement system has been developed for analyzing the light elements in thin films. The system consists of two time detectors and a silicon detector, and the energy and time-of-flight of recoil ions are measured simultaneously. This system has been tested using He, C, and Cu beams with energies between 2 and 20 MeV. Depth resolutions at the surface of a thin carbon layer were 1.3 ± 0.1 nm with a 2-MeV 4He beam and 1.6 ± 0.2 nm with a 5-MeV 63Cu beam. The sensitivity of oxygen measurements was evaluated to be 3.8 × 1014 cm−2 when using a 12-MeV 63Cu beam.

Background Early detection and intervention for neurodevelopmental disorders are effective. Several types of paper questionnaires have been developed to assess these conditions in early childhood; however, the psychometric equivalence between the web-based and the paper versions of these questionnaires is unknown. Objective This study examined the interformat reliability of the web-based parent-rated version of the Autism Spectrum Screening Questionnaire (ASSQ), Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), Developmental Coordination Disorder Questionnaire 2007 (DCDQ), and Strengths and Difficulties Questionnaire (SDQ) among Japanese preschoolers in a community developmental health check-up setting. Methods A set of paper-based questionnaires were distributed for voluntary completion to parents of children aged 5 years. The package of the paper format questionnaires included the ASSQ, ADHD-RS, DCDQ, parent-reported SDQ (P-SDQ), and several additional demographic questions. Responses were received from 508 parents of children who agreed to participate in the study. After 3 months, 300 parents, who were among the initial responders, were randomly selected and asked to complete the web-based versions of these questionnaires. A total of 140 parents replied to the web-based format and were included as a final sample in this study. Results We obtained the McDonald ω coefficients for both the web-based and paper formats of the ASSQ (web-based: ω=.90; paper: ω=.86), ADHD-RS total and subscales (web-based: ω=.88-.94; paper: ω=.87-.93), DCDQ total and subscales (web-based: ω=.82-.94; paper: ω=.74-.92), and P-SDQ total and subscales (web-based: ω=.55-.81; paper: ω=.52-.80). The intraclass correlation coefficients between the web-based and paper formats were all significant at the 99.9% confidence level: ASSQ (r=0.66, P Conclusions These results suggest that the web-based versions of the ASSQ, ADHD-RS, DCDQ, and P-SDQ were equivalent, with the same level of internal consistency and intrarater reliability as the paper versions, indicating the applicability of the web-based versions of these questionnaires for assessing neurodevelopmental disorders.

BACKGROUND Early detection and intervention for neurodevelopmental disorders are effective. Several types of paper questionnaires have been developed to assess these conditions in early childhood; however, the psychometric equivalence between the web-based and the paper versions of these questionnaires is unknown. OBJECTIVE This study examined the interformat reliability of the web-based parent-rated version of the Autism Spectrum Screening Questionnaire (ASSQ), Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), Developmental Coordination Disorder Questionnaire 2007 (DCDQ), and Strengths and Difficulties Questionnaire (SDQ) among Japanese preschoolers in a community developmental health check-up setting. METHODS A set of paper-based questionnaires were distributed for voluntary completion to parents of children aged 5 years. The package of the paper format questionnaires included the ASSQ, ADHD-RS, DCDQ, parent-reported SDQ (P-SDQ), and several additional demographic questions. Responses were received from 508 parents of children who agreed to participate in the study. After 3 months, 300 parents, who were among the initial responders, were randomly selected and asked to complete the web-based versions of these questionnaires. A total of 140 parents replied to the web-based format and were included as a final sample in this study. RESULTS We obtained the McDonald ω coefficients for both the web-based and paper formats of the ASSQ (web-based: ω=.90; paper: ω=.86), ADHD-RS total and subscales (web-based: ω=.88-.94; paper: ω=.87-.93), DCDQ total and subscales (web-based: ω=.82-.94; paper: ω=.74-.92), and P-SDQ total and subscales (web-based: ω=.55-.81; paper: ω=.52-.80). The intraclass correlation coefficients between the web-based and paper formats were all significant at the 99.9% confidence level: ASSQ (r=0.66, Pr=0.66-0.74, Pr=0.66-0.71, Pr=0.55-0.73, PP=.76), total (P=.12) and subscale (P=.11-.47) mean scores of DCDQ, and the P-SDQ Total Difficulties mean score (P=.20) and mean subscale scores (P=.28-.79). Although significant differences were found between the web-based and paper formats for mean ADHD-RS scores (total: t132=2.83, P=.005; Inattention subscale: t133=2.15, P=.03; Hyperactivity/Impulsivity subscale: t133=3.21, P=.002), the effect sizes were small (Cohen d=0.18-0.22). CONCLUSIONS These results suggest that the web-based versions of the ASSQ, ADHD-RS, DCDQ, and P-SDQ were equivalent, with the same level of internal consistency and intrarater reliability as the paper versions, indicating the applicability of the web-based versions of these questionnaires for assessing neurodevelopmental disorders.

In this work, we measured and simulated the dissociation of biomolecules in liquid water induced by secondary electrons ejected from water molecules during fast heavy-ion irradiation. We calculated the energy spectra of secondary electrons generated along carbon ion tracks in liquid water in the Bragg peak region. The calculation was done using the Particle and Heavy Ion Transport code System (PHITS) in carbon track structure mode. This mode enables simulation of inelastic collisions along a carbon ion track based on the cross sections considered in the Monte Carlo code KURBUC. To understand the biomolecular dissociation processes in our previous MeV-SIMS experiments with microdroplet targets of glycine solution, we calculated the collision spectra of secondary electrons produced near liquid surfaces using PHITS. Furthermore, we examined the relationship between the secondary electron energy and formation of positive and negative glycine fragments. The results showed that the formation of methylene amine cations is caused by secondary electrons with energies of 13–100 eV. The formation of glycine-related negative ions such as cyanide anion, formate anion, and deprotonated glycine was found to be caused by low-energy (less than 13 eV) secondary electrons. These ions are known products of dissociative electron attachment.

In this study, the recurrent fluorescence of naphthalene ions was investigated using an electrostatic ion beam trap. The number of photons from the recurrent fluorescence on the ${D}_{2}\ensuremath{\rightarrow}{D}_{0}$ transition was measured as a function of time, after the production of naphthalene ions by electron impact. The emission of photons was observed over a time range of approximately 10 ms. The variation in the number of photons for such a long time range could be explained by conducting simulations using previously reported theoretical rate constants of both the fragmentation and the recurrent fluorescence of vibrationally hot naphthalene ions.

Context: There is a worldwide shortage of physicians, which is worse in rural areas, with a large underserved rural and remote population. Most jurisdictions in countries of all income levels report shortages of rural doctors, often exacerbated where primary care is not strong. Japan is not an exception: Japanese specialist-driven approaches in medical education and public health have resulted in disproportionate distribution of medical services in the country. Issue: Rural generalism, or rural generalist medicine, is emerging in many jurisdictions as one approach to training and provision of care for rural communities. While there is considerable variation in titles, the format of the training and models of care, the emphasis is on training a generalist doctor capable of meeting community needs. This usually includes development of appropriate skills in primary care, inpatient care, emergency medicine, public health and one or more extended skills. These models are well established in Australia, particularly in Queensland, which has offered a rural generalist program for over a decade. The Rural Generalist Program Japan (RGPJ) has been developed to meet the needs of Japanese rural communities. Lessons learned: This article outlines development of the RGPJ using the World Federation for Medical Education standards. While early evaluations are positive, there is much more to do to develop a mature program capable of meeting the needs of Japan's rural and remote communities.

Polyunsaturated fatty acid (PUFA) is an essential class of dietary fatty acids, because of the lack of endogenous enzymes for desaturation in humans. Previous research on n-3 PUFA has demonstrated several health benefits and antiatherogenic actions, but n-6 PUFA have not received much research attention. We investigated whether serum fatty acid composition, especially n-6 PUFAs and desaturase activity, is associated with obesity in type 2 diabetic patients. Subjects were 80 type 2 diabetic patients (age: 60.3±13.9 years) who had no EPA agent intake. They were divided into two groups: obese group (n=52) with a BMI more than 25 kg/m2 and non-obese group (n=28) with a BMI less than 25 kg/m2. Fatty acid levels in serum were measured using gas chromatography. The desaturase activity for n-6 PUFAs was calculated as the arachidonic acid/dihomo-gamma-linolenic acid (DGLA) ratio for Δ5 desaturase (D5D). The obese group revealed a higher saturated fatty acid (SFA) and DGLA levels than those in the non-obese group. No significant difference was observed in the serum n-3 PUFA levels between the two groups. The D5D index of the obese group was significantly lower than that of the non-obese group. Serum DGLA levels showed significant positive correlations with waist circumference, BMI, triglyceride, and hepatic AST and ALT levels. Moreover, SFA showed a significant positive correlation with BMI. The levels of D5D index showed a significant negative correlation with BMI. Increase in serum DGLA levels was related to the number of metabolic factors. These results suggest that type 2 diabetic patients with obesity had changes in their blood fatty acid profile, especially increased DGLA levels. The high levels of blood DGLA indicate downregulation of n-6 metabolism, probably caused by the decreased activity of D5D. The fat quality in the diet and changes in desaturase activity might contribute to the development of obesity. Disclosure M. Saito: None. M. Higa: None. T. Suzuki: None. M. Michishita: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.

Nonalcoholic fatty liver disease (NAFLD), which is currently the most prevalent liver disorder, not only leads to chronic liver disease but is also associated with cardiovascular mortality. Several studies have conclusively established that increased arterial stiffness is an independent risk factor for cardiovascular events and that the brachial-ankle pulse velocity (baPWV) is a useful clinical indicator of arterial stiffness for early evaluation of functional and structural changes in vessel walls. The aim of this study was to assess whether ultrasonographically diagnosed fatty liver disease is associated with arterial stiffness and carotid intima-media thickness (CIMT) in type 2 diabetic patients. The subjects were 294 type 2 diabetic patients (age: 66.4±10.3 years). Patients with and without fatty liver (FL) were categorized into the FL group (n=155), and non-FL group (n=139), respectively. The baPWV was measured as an index of arterial stiffness, and structural changes in vessel walls were assessed using the CIMT obtained with B-mode ultrasonography. BMI, waist circumference, blood pressure, serum LDL-C, triglyceride (TG), and HbA1c levels, as well as the baPWV and CIMT levels were significantly higher in the FL than in the non-FL group. Serum levels of TG, hepatic AST, age, waist circumference and systolic blood pressure showed significant positive correlations with baPWV, respectively. However, no significant association was observed between the CIMT and serum hepatic AST levels. Multiple regression analysis showed that serum hepatic AST and ALT were independently associated with increased baPWV. Our findings suggest that NAFLD is associated with increased arterial stiffness. This is a clinically significant observation because it implicates arterial stiffness in the pathogenesis of NAFLD, suggesting that abdominal obesity and low-grade inflammation might be key etiopathogenetic contributors to both hepatic steatosis and macrovascular disease in type 2 diabetic patients. Disclosure M. Higa: None. M. Hijikata: None. K. Yamashita: None. T. Suzuki: None. M. Saito: None. M. Michishita: None. K. Ikehara: None. T. Ichijo: None.

Background: Whether there is a true increase in Autism Spectrum Disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample hasn't been fully examined before. Methods: All 5-year-old children in the catchment area in Japan underwent the screening annually from the year 2013 - 2016. Screen-positive children were invited to a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary team. ASD prevalence and cumulative incidence were computed. Outcomes: Caregivers of 3,954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% Confidence Interval (CI): 2.66 - 3.76). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31 (95% CI: 1.00 - 1.62). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD. Interpretation: Our findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in ASD children. Funding: Grants-in-Aid for Scientific Research and Hirosaki Institute of Neuroscience. Declaration of Interest: The authors have no financial relationships relevant to this article to disclose. Ethical Approval: This study was approved by the Committee of Medical Ethics of Hirosaki University Graduate School of Medicine. Moreover, the information security policies of the city and committee were followed to protect the personal data of the participants.

Background Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. Methods We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0–5, 6–11, and 12–18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. Results In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. Limitations It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects’ age. Conclusions There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.