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BackgroundGenome-wide association studies (GWASs) have identified 29 disease-associated single nucleotide polymorphisms (SNPs) for systemic sclerosis (SSc) in non-human leukocyte antigen (HLA) regions (1-7). While these GWASs have clarified genetic architectures of SSc, study subjects were mainly Caucasians limiting application of the findings to Asians.ObjectivesThe study was conducted to identify novel causal variants for SSc specific to Japanese subjects as well as those shared with European population. We also aimed to clarify mechanistic effects of the variants on pathogenesis of SSc.MethodsA total of 114,108 subjects comprising 1,499 cases and 112,609 controls were enrolled in the two-staged study leading to the ever-largest Asian GWAS for SSc. After applying a strict quality control both for genotype and samples, imputation was conducted using the reference panel of the phase 3v5 1,000 genome project data combined with a high-depth whole-genome sequence data of 3,256 Japanese subjects. We conducted logistic regression analyses and also combined the Japanese GWAS results with those of Europeans (6) by an inverse-variance fixed-effect model. Polygenicity and enrichment of functional annotations were evaluated by linkage disequilibrium score regression (LDSC), Haploreg and IMPACT programs. We also constructed polygenic risk score (PRS) to predict SSc development.ResultsWe identified three (FCRLA-FCGR, TNFAIP3, PLD4) and four (EOMES, ESR1, SLC12A5, TPI1P2) novel loci in Japanese GWAS and a trans-population meta-analysis, respectively. One of Japanese novel risk SNPs, rs6697139, located within FCGR gene clusters had a strong effect size (OR 2.05, P=4.9×10-11). We also found the complete LD variant, rs10917688, was positioned in cis-regulatory element and binding motif for an immunomodulatory transcription factor IRF8 in B cells, another genome-wide significant locus in our trans-ethnic meta-analysis and the previous European GWAS. Notably, the association of risk allele of rs10917688 was significant only in the presence of the risk allele of the IRF8. Intriguingly, rs10917688 was annotated as one enhancer-related histone marks, H3K4me1, in B cells, implying that FCGR gene(s) in B cells may play an important role in the pathogenesis of SSc. Furhtermore, significant heritability enrichment of active histone marks and a transcription factor C-Myc were found in B cells both in European and Japanese populations by LDSC and IMPACT, highlighting a possibility of a shared disease mechanism where abnormal B-cell activation may be one of the key drivers for the disease development. Finally, PRS using effects sizes of European GWAS moderately fit in the development of Japanese SSc (AUC 0.593), paving a path to personalized medicine for SSc.ConclusionOur study identified seven novel susceptibility loci in SSc. Downstream analyses highlighted a novel disease mechanism of SSc where an interactive role of FCGR gene(s) and IRF8 may accelerate the disease development and B cells may play a key role on the pathogenesis of SSc.References[1]F. C. Arnett et al. Ann Rheum Dis, 2010.[2]T. R. Radstake et al. Nat Genet, 2010.[3]Y. Allanore et al. PLoS Genet, 2011.[4]O. Gorlova et al. PLoS Genet, 2011.[5]C. Terao et al. Ann Rheum Dis, 2017.[6]E. López-Isac et al. Nat Commun, 2019.[7]W. Pu et al. J Invest Dermatol, 2021.Disclosure of InterestsNone declared

Background:Low-density lipoprotein receptor-related protein 1B(LRP1B) is thought to have a pleiotropic biological function. Notably, intracellular domain of LRP1B is released and transported to nucleus in a γ-secretase dependent fashion; however, pathological property, which is driven by nuclear transport of intracellular domain of LRP1B is largely unclear. In this study, we aimed to unravel the pathological significance of nuclear localization of intracellular domain of LRP1B in mammary gland carcinogenesis. Aims: We examine the clinical significance of LRP1B for breast cancer and we clarify mechanism of nuclear localization of LRP1B in invasive ductal carcinoma. Methods: Immunohistochemical staining using newly generated antibodies to intracellular domain of LRP1B was used to determine LRP1B expression in 92 invasive ductal carcinomas of the breast. The clinicopathological significance including prognosis value was statistically analyzed. Doxycycline dependent nuclear expression of intracellular domain of LAP1B was established in cultured breast cancer cells. Subsequently, a series of in vitro experiments were performed to explore the role of nuclear localized intracellular domain of LRP1B in cultured breast cancer cells. Comprehensive microarray-based analysis followed by quantitative RT-PCR and chromatin immunoprecipitation assay was performed to know the altered molecular signature induced by nuclear localized intracellular domain of LRP1B. Results: Non-tumorous mammary duct epithelial cells did not exhibit LRP1B staining, whereas different degrees of LRP1B immunoreactivity were observed in 75 of 92 invasive ductal carcinoma of the breast. LRP1B immunoreactivity was found in surface membrane and cytoplasm of 60 of 92(65.2%) invasive ductal carcinoma cells, whereas it was detected in nucleus of 15 of 92(16.3%)cancer cells. Interestingly, nuclear LRP1B immunoreactivity was significantly associated with poor prognosis of the patients, especially with luminal A type breast cancers. Notably, nuclear localized intracellular domain of LRP1B significantly related to status of nodal metastasis in luminal A type breast cancers. Enforced nuclear expression significantly increased Matrigel invasion activity in MCF-7 luminal A breast cancer cells without affecting cell growth. Notably, nuclear expression of intracellular domain of LRP1B decreased transcription of LRP1B. Comprehensive microarray-based analysis demonstrated that nuclear expression of intracellular domain of LRP1B significantly increased the expression of long non-coding RNA nuclear paraspeckle assembly transcript1(NEAT1), which facilitates breast cancer invasion with poor survival. Conclusions: Present findings indicated that nuclear localized intracellular domain of LTP1B promoted breast cancer progression with a poor prognostic value, possible through NEAT1 pathway. Nuclear transport of intracellular domain of LRP1B could be a therapeutic target for breast cancer patients. Citation Format: Asano Y, Futamura M, Takeuchi T, Yoshida K. Nuclear localization of intracellular domain of LDL receptor-related protein 1B predicts poor outcome in breast cancer; putative relation to NEAT1 mediated mammary gland carcinogenesis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD1-04.

We have constructed a new laser-Compton-scattering facility, called the LEPS2 beamline, at the 8-GeV electron storage ring, SPring-8. This facility provides a linearly polarized photon beam in a tagged energy range of 1.3--2.4 GeV. Thanks to a small divergence of the low-emittance storage-ring electrons, the tagged photon beam has a size (sigma) suppressed to about 4 mm even after it travels about 130 m to the experimental building that is independent of the storage ring building and contains large detector systems. This beamline is designed to achieve a photon beam intensity higher than that of the first laser-Compton-scattering beamline at SPring-8 by adopting the simultaneous injection of up to four high-power laser beams and increasing a transmittance for the long photon-beam path up to about 77%. The new beamline is under operation for hadron photoproduction experiments.

BackgroundIn clinical practice for systemic lupus erythematosus (SLE), the concept of “treat to target” has been introduced with an established goal of reducing glucocorticoid dose as much as possible while controlling disease activity. Although it has been shown that various personality characteristics of patients with SLE affect their disease activity and damage, it is not clear whether the personality characteristics of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait characterized by perseverance and passion for achieving long-term goals.ObjectivesThis study aims to evaluate the relationship between attending physicians’ grit personality characteristics and treatment goal achievements in patients with SLE.MethodsA cross-sectional study was conducted on 386 patients with SLE in five referral hospitals in Japan. The main exposure was the “perseverance” and “consistency” (scores 1-5) of the attending physicians, as measured by the Short Grit Scale, and the primary outcome was the achievement of the Lupus Low Disease Activity Score (LLDAS). Considering the clustering of achievement of LLDAS by each attending physician, the association between attending physician’s personality and LLDAS was analyzed by logistic regression with cluster robust variance estimation. Odds ratios to assess the relationship between perseverance and consistency and LLDAS were estimated with adjustment for confounders (age, sex, disease duration, hydroxychloroquine use, immunosuppressant use, and Systemic Lupus International Collaborating Clinics-Damage Index). We used multiple imputation to handle the uncertainty caused by missing values of potential confounders on the assumption of missing at random.ResultsThe median age of the patients was 45 years (interquartile range[IQR],36-56), 88% were female, and the median disease duration was 152 months(IQR, 80-240). Thirty-seven doctors were in charge of the patients (1-79 patients/each doctor). The median age of the attending physicians was 40 years (IQR, 35-43), and 19% were female. The median perseverance and consistency scores of attending physicians were 3.1 (IQR, 3.0-3.5) and 3.3 (IQR, 2.8-3.8), respectively. Of the enrolled patients, 154 (40%) had achieved LLDAS. The attending physicians with a lower consistency score of ConclusionThe grit personality characteristics of the attending physician may affect the achievement of treatment goals in patients with SLE.Disclosure of InterestsKEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Grant/research support from: I received a research grant from Pfizer Inc., Yoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yu Katayama: None declared, Yosuke ASANO: None declared, Keigo Hayashi: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto: None declared, Nao Oguro: None declared, Yuichi Ishikawa: None declared, Natsuki Sakurai: None declared, Chiharu Hidekawa: None declared, Ryusuke Yoshimi: None declared, Takanori Ichikawa: None declared, Dai Kishida: None declared, Yasuhiro Shimojima: None declared, Noriaki Kurita: None declared, Nobuyuki Yajima: None declared

BackgroundThe minimally important difference (MID) required to interpret the magnitude of changes in lupus patient-reported outcome (LupusPRO), which is a widely used outcome measure of quality of life in SLE patients, remains unclear.ObjectivesWe report preliminary results of an ongoing prospective observational study that assesses the MID as the interpretability of emotional health (EH) domain in Japanese version of LupusPRO.MethodsWe recruited subjects at three university hospitals in Japan participating in an ongoing multidisciplinary cohort study (the Lupus registry of Nationwide institutions (LUNA). Of a total of 210 SLE patients enrolled during the 17-month recruitment period, patients with low disease activity, defined as SLE Disease Activity Index 2000 (SLEDAI-2K) ≤ 4, and who were seen at least twice of three months’ duration and responded to both the LupusPRO and health status change questions were included in this subcohort. The second questionnaire was given an allowance period of 30 days before or after the ​three months from starting date. Descriptive statistics were presented as means and standard deviations (SD) or counts and percentages (%). The emotional health score ranges from 0 to 100; a higher score indicates less frequent presence of symptoms. The change in health status was assessed using the 7-point Global Rating of Change 1), and the score = 0 and the score ≥ +1 were considered in the ‘unchanged’ and the minimal ‘improved’ category, respectively. MID was mainly estimated using the mean change of the groups with the score ≥ +1 as the anchor-based method, and the area under the curve (AUC) was also calculated as a sensitivity analysis to estimate MID thresholds 2) and 95% confidence intervals (CI) were constructed using 1000 bootstrapping.ResultsThe mean age of the 24 eligible patients was 48 (SD 14), and 88% were female. The glucocorticoid dose, SLEDAI-2K, and Systemic Lupus International Collaborating Clinics /American College of Rheumatology Damage Index were 3.4 (2.1) mg, 1.0 (1.1) and 1.1 (1.9), respectively. The mean EH score was 67.5 (30.3), five patients (21%) had the maximum EH score at baseline, 73.4 (25.0) after three months, 7.2 (18.0) for the change in EH. The correlation coefficient and the AUC for the change in health status and the EH were 0.23 and 0.60. The mean changes were 4.1 (18.4) of the groups with ‘unchanged’ health status and 12.3 (17.1) of the groups with ‘improved’ health status. The MID for improvement was estimated at 12.3 using the anchor-based method, and the cutoff point corresponded to 9.3 [95%CI -6.7 to 25.3]) of the EH change score by the receiver operating curve method.ConclusionIn this study, the MID (3 months) for the EH domain in the Japanese version of LupusPRO was estimated to be between 9 and 12, which was similar to the results of the previous cross-sectional study 3). The challenge in estimating the MID in our setting was the low correlation with external anchors, even though the study population was limited to patients with low disease activity, because disease activity at baseline can generally influence ‘improved’ health status.References[1]Kamper SJ, Maher CG, Mackay G. Global rating of change scales: a review of strengths and weaknesses and considerations for design. J Man Manip Ther. 2009;17(3):163.[2]Froud R, Abel G. Using ROC curves to choose minimally important change thresholds when sensitivity and specificity are valued equally: the forgotten lesson of pythagoras. theoretical considerations and an example application of change in health status. PLoS One. 2014;9(12):e114468.[3]Miyawaki Y, Shimizu S, Ogawa Y, et al. Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study. Arthritis Res Ther. 2021;23(1):79.AcknowledgementsThe authors thank Yuka Nakanou for her significant assistance in data management and Kikuko Miyazaki for her expert assistance on this topic.Disclosure of InterestsYoshia Miyawaki: None declared, Kenta Shidahara: None declared, Shoichi Nawachi: None declared, Yosuke ASANO: None declared, Yu Katayama: None declared, Keiji Ohashi: None declared, Eri Katsuyama: None declared, Takayuki Katsuyama: None declared, Mariko Narazaki: None declared, Yoshinori Matsumoto Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., KEN-EI SADA Speakers bureau: I received speaker’s fees from Glaxo Smith Kline K.K., Ryo Yanai: None declared, Nobuyuki Yajima: None declared, Ayuko Takatani: None declared, Kunihiro Ichinose: None declared, Jun Wada Speakers bureau: Jun Wada receives speaker honoraria from Astra Zeneca, Daiichi Sankyo, Novartis, Novo Nordisk Pharma, Tanabe Mitsubishi and receives grant support from Astellas, Baxter, Bayer, Chugai, Dainippon Sumitomo, Kyowa Kirin, Novo Nordisk Pharma, Ono, Otsuka, Tanabe Mitsubishi, and Teijin.

We fabricated a cascade arc discharge source with a channel diameter of 8 mm for various applications to virtual vacuum interface (plasma window). Stationary helium arc plasma up to a discharge current of 100 A was generated, and the performance as plasma window was investigated. The pressure ratio of high-pressure discharge section to low-pressure vacuum side was above 70 at a 50-A He discharge with a gas flow rate of 0.2 L/min. To characterize the plasma at the anode electrode, emissions of vacuum UV and visible wavelengths were observed. Spectral analysis of He I continuum spectra and H- $\beta $ Stark broadening showed that the plasma temperature was around 0.9 eV and density was $3.4\times 10^{13}$ cm−3 for a 100-A He discharge with a gas flow rate of 0.05 L/min.

SUMMARYThe present study investigated the dry matter yield (DMY) and arbuscular mycorrhizal (AM) colonization (internal hyphae, arbuscules, and vesicles) of two genotypes of zoysia grass (Zoysia japonica strain Aso and cv. Asagake) at three rates (10, 20 and 40 g N/m2/year) of application of digested slurry (DS) or mineral fertilizer. Soil chemical properties (available phosphorus concentration, pH and electrical conductivity (EC)) were also measured as factors associated with AM colonization. The fertilizer type (DS v. mineral fertilizer) had an effect on DMY depending on the plant genotypes but had little or no effect on AM colonization, and soil chemical properties, indicating that DS can be used as a substitute for mineral fertilizer; however, it is necessary to apply it taking into account the ratio of inorganic nitrogen (N). However, heavy DS application decreased colonization by internal hyphae. Furthermore, even at the lowest rate, the continuous application of DS decreased colonization by arbuscules and vesicles in both genotypes, which were associated with decreasing soil pH and increasing EC. The results suggest that zoysia grass should be fertilized with DS at a rate of 2/year in order to achieve a continuous association with AM fungi, although this range of N application is sub-optimal for zoysia grass production.

Most atypical fractures associated with the long-term treatment with bisphosphonates (BP) commonly develop in the femoral shaft or subtrochanteric region. We report a rare case of bilateral atypical ulnar fractures in an 86-year-old woman with osteoporosis who finished the treatment with teriparatide for 2 years after long-term treatment with BP. She slid down from an approximately 30-cm-tall seat and slightly contused her left elbow. Plain radiography revealed that both ulnae had a noncomminuted short oblique fracture with cortical thickening and sclerosis at the fracture site. Based on the clinical and radiological findings, she was diagnosed with bilateral atypical ulnar fractures. The fracture of the left ulna was completely displaced and treated surgically. On the other hand, since the right ulna was an incomplete fracture, it was treated conservatively. During surgery, drilling with Kirschner wire and curettage were performed in the osteosclerotic lesion, and an autologous cancellous bone graft was inserted from the ipsilateral olecranon. Bone union was achieved in both fractures at 1 year after surgery. There have been no reports regarding the development of atypical ulnar fractures occurring after the long-term treatment with BP and 2-year use of teriparatide, and the treatment strategies of such fractures have not been established. If teriparatide cannot be used after occurring atypical fractures, the use of low-intensity pulsed ultrasound (LIPUS) and subsequent treatment for osteoporosis are recommended for the bone union. In addition, the treatment of the osteosclerotic lesion and rigid internal fixation are required in surgery.

Spectral unmixing of hyperspectral data often fails to select some minerals and rocks having flat spectra but no diagnostic absorption features as endmembers, even if they are actually important endmembers. To avoid this problem, we propose a novel approach that combined two methods: spectral unmixing and full-pixel classification. First, all pixels were divided into two categories, hydrothermally altered areas and unaltered rocks based on the absorption depth of 2.0 to 2.5 μm. For the hydrothermally altered areas, endmembers were extracted by the Improved Causal Random Pixel Purity Index (ICRPPI) method, which was improved from the existing Pixel Purity Index (PPI) and Causal Random Pixel Purity Index (CRPPI) methods. Endmember abundance in each pixel was calculated by linear spectral unmixing. In a separate operation, k-means clustering was applied to the unaltered rock areas. Finally, the results of these two methods were combined to generate a single distribution map of rocks and minerals. This approach was applied to the airborne hyperspectral HyMap data of Cuprite, Nevada, U.S.A. We confirmed that our mapping result was consistent with the existing geological map as well as our field survey result.

Background Subcutaneous injection of biologic agents gives more freedom and independence for patients with rheumatoid arthritis (RA) than intravenous injection. Despite this, patients with RA sometimes select intravenous injections due to concerns over self-injection, such as injection anxiety, including pain, and lack of confidence in giving a self-injection [1]. It is reported that one in five people are estimated to experience injection anxiety [2]. Therefore, an understanding of subcutaneous injection pain and anxiety and support for anxiety of patients with RA are important for appropriate usage of subcutaneous biologics. Objectives The aim is to evaluate pain and anxiety caused by adalimumab (ADA) subcutaneous injection and assess the effectiveness of nurses9 care. Methods Patients with RA using ADA self-injections were enrolled. Pain was assessed in 4 categories: general, needle insertion, drug injection, needle removal. Pain was evaluated using Visual Analogue Scale (VAS) scale. Effectiveness of support by nurses was also assessed using self-questionnaires and free-format comments. Statistical analyses were performed utilizing Wilcoxon9s signed rank test and Spearman9s rank correlation coefficient. Results Twenty patients (Male: Female, 4: 16) completed the questionnaire. Average age and disease duration were 68 and 12.6 years, respectively. Mean ± SD of Pain VAS were 34.9±28.1 mm (General), 30.3±30.6 mm (needle insert), 42.5±35.6mm (drug injection) and 11.8±18.4mm (needle removal). There were no statistically significant differences between general pain and needle insertion (p=0.631), or general pain and drug injection (p=0.121). However, statistically significant differences were found between general pain and needle removal (p=0.001). Moreover, there were statistically significant differences between needle insertion and removal (p=0.003), and drug injection and needle removal (p=0.00048). General pain showed statistically significant correlation with needle insertion pain (r=0.653, p=0.0018) and drug injection pain (r=0.615, p=0.004). However, general pain was not correlated with needle removal pain (r=0.137, p=0.565). Patients with RA answered that support by nurses was effective for relieving pain (30%), reduction of anxiety (35%) and improving treatment motivation (50%). According to the patients, nurses helped raise motivation by explaining that treatment prevents the progression of RA and allows many patients to feel better and have less pain. Interaction with nurses appears to be effective in reducing injection pain and anxiety and improving motivation for self-injection treatment. Conclusions These data indicate that needle insertion and drug injection pain have great influences on general pain. Support by nurses is likely to reduce injection anxiety and pain, resulting in higher motivation toward self-injection treatment. References Keininger D, et al. Health Qual Life Outcomes. 2011 Jan 13; 9:2. Nir Y, et al. Am J Trop Med Hyg 2003, 68: 341–4. Disclosure of Interest None declared

A search for the K − p p bound state (the lightest kaonic nucleus) has been performed using the γ d → K + π − X reaction at E γ = 1.5 – 2.4 GeV at LEPS/SPring-8. The differential cross section of the K + π − photo-production off deuterium ( d 2 σ / d cos θ K + l a b / d cos θ π − l a b ) has been measured for the first time in this energy region. A peak structure was searched for in the inclusive missing mass spectrum. A statistically significant peak structure was not observed in the region from 2.22 to 2.36 GeV/c2. The upper limits of the differential cross section of the K − p p bound state production were determined to be (0.17–0.55), (0.55–1.7) and (1.1–2.9) μb at 95% confidence level with the assumed widths of 20 MeV, 60 MeV and 100 MeV.

We have previously reported a study on brain activity detection in occipital region using a picotesla-scale Magneto- Impedance (MI) sensor. Based on past studies, the target of the present study was to review the performance of MI sensor on parietal region brain activity detection. Human brain magnetic field is extremely weak, in order to detect the faint magnetic field, we constructed an MI measurement system that can cancel out the background noise (e.g., geomagnetic field) instead of using a magnetic shielding. In this study, we recorded P300 brain waves of subjects, compared our results with our past studies and other EEG and MEG data reported previously. The results confirmed the reliability of our data and indicated that the MI sensor can be applied on brain activity detection.

The $\ensuremath{\phi}\text{\ensuremath{-}}\mathrm{\ensuremath{\Lambda}}(1520)$ interference effect in the $\ensuremath{\gamma}p\ensuremath{\rightarrow}{K}^{+}{K}^{\ensuremath{-}}p$ reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between $\ensuremath{\phi}$ and $\mathrm{\ensuremath{\Lambda}}(1520)$ production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when ${K}^{+}{K}^{\ensuremath{-}}$ pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the $\sqrt{s}=2.1\text{ }\text{ }\mathrm{GeV}$ bump structure in forward differential cross sections for $\ensuremath{\phi}$ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

The ϕ-Λ(1520) interference effect in the γp→K^{+}K^{-}p reaction has been measured for the first time in the energy range from 1.673 to 2.173 GeV. The relative phases between ϕ and Λ(1520) production amplitudes were obtained in the kinematic region where the two resonances overlap. The measurement results support strong constructive interference when K^{+}K^{-} pairs are observed at forward angles but destructive interference for proton emission at forward angles. Furthermore, the observed interference effect does not account for the sqrt[s]=2.1 GeV bump structure in forward differential cross sections for ϕ photoproduction. This fact suggests possible exotic structures such as a hidden-strangeness pentaquark state, a new Pomeron exchange, or rescattering processes via other hyperon states.

BACKGROUND AND PURPOSE: The relationship between white matter disruption and cognitive dysfunction of patients with mTBI in the chronic stage remains unclear. The aim of this study was to identify white matter integrity by using DTI in patients with mTBI without morphologic traumatic abnormalities seen with conventional imaging and to evaluate the association of such regions with cognitive function. MATERIALS AND METHODS: Diffusion tensor images from 51 consecutive patients with mTBI without morphologic traumatic abnormalities on conventional MRI were processed, and FA maps were generated as a measure of white matter integrity. All subjects underwent cognitive examinations (MMSE and WAIS-R FIQ). Correlations between the skeletonized FA values in the white matter and the cognitive function were analyzed by using regression analysis. RESULTS: In patients with mTBI, significantly decreased FA value clusters in the white matter compared with the healthy controls were found in the superior longitudinal fasciculus, superior frontal gyrus, insula, and fornix. Cognitive examination scores positively correlated with FA values in a number of regions in deep brain structures, which were anatomically close or physiologically intimate to the regions with significant FA value reduction, in patients with mTBI. CONCLUSIONS: The present study shows that patients with mTBI in the chronic stage have certain regions with abnormally reduced white matter integrity in the brain. Although the clinical and pathologic-anatomic correlation of these findings remains to be elucidated, these brain regions are strongly suggested to be related to chronic persistent cognitive impairments in these patients. ABBREVIATIONS: DAI diffuse axonal injury; FA fractional anisotropy; FIQ full-scale intelligence quotient; GCS Glasgow Coma Scale; MMSE Mini-Mental State Examination; MNI Montreal Neurological Institute; mTBI mild traumatic brain injury; TBI traumatic brain injury; TBSS tract-based spatial statistics; WAIS-R Wechsler Adult Intelligence Scale-Revised

This paper proposes a heterogeneous wireless network with handover in the application layer. The proposed network requires no upgrade of wireless infrastructure and mobile terminals to convert the present homogeneous networks to the proposed heterogeneous network. Only installing application programs on the content server side and the mobile terminal side is required. The performance of the proposed network has been evaluated in a field trial using a mobile broadband wireless access (MBWA) air interface with wide coverage and a wireless local area network (WLAN) air interface with high throughput. The field trial results show that the maximum value of the handover outage time is only 170ms. The proposed heterogeneous wireless network is promising since both high throughput and wide coverage area are attained by a combination of the proposed handover scheme with the present homogeneous wireless networks.