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This paper addresses the Production Routing Problem (PRP). In this problem we make integrated decisions about the number of products to be manufactured, the number of products to be delivered to each customer and the routes of the vehicles used to deliver the manufactured products. The integrated problem attempts to minimize both production and distribution costs, over all periods of a finite planning horizon. An Integer Programming Model is presented and model-based heuristics are proposed to tackle the PRP. Computational results are shown for both benchmark and proposed instances, in order to compare the proposed solution method with a high-performance commercial solver. The results show that our approach outperforms the commercial solver in getting high-quality solutions in instances with more than 10 customers and 5 products.

Haruka Watanabe1 1, Yuta Norimatsu1 12 2, Yuki Ohno1 1 1Department of Dermatology, JR Tokyo General Hospital, Tokyo, Japan; 2Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, JapanCorrespondence: Yuta NorimatsuJR Tokyo General Hospital, 2-1-3 Yoyogi Shibuya-ku, Tokyo, 151-8528, JapanTel +81-3-3320-2210Fax +81-3-3370-7478Email norimatsuy-der@h.u-tokyo.ac.jpBackground: Infections caused by Prevotella bivia, a gram-negative anaerobic bacillus, are rare, with no reported cases in Japan. We present a novel case of scrotal abscess in a Japanese patient co-infected with Prevotella bivia and Streptococcus agalactiae.Case Presentation: A 41-year-old uncontrolled diabetic man complained of swelling and pain in the scrotum. On examination, computed tomography revealed an abscess of 5-cm diameter in the scrotum. Then, the abscess was incised and drained. He was treated with cefazolin empirically. Prevotella bivia and Streptococcus agalactiae were identified in the pus cultures obtained from the abscess. However, the susceptibility tests for Prevotella bivia could not be submitted. Seven days following admission, the pain reduced, and the drainage slowed. The patient was discharged on day 14 when cefazolin was discontinued and oral amoxicillin (750 mg/day) was started. Amoxicillin was continued until day 42; improvement was confirmed.Conclusion: To the best of our knowledge, this case is the first report of Prevotella bivia in Japan. We suggest that cephem antibiotics such as cefazolin may be effective against Prevotella bivia in Japan.Keywords: case report, Prevotella bivia, Streptococcus agalactiae, cefazolin, amoxicillin

Shiho Ubukata,1,2 Naoya Oishi,2 Tatsuya Higashi,3,4 Shinya Kagawa,3 Hiroshi Yamauchi,3 Chio Okuyama,3 Hiroyuki Watanabe,5 Masahiro Ono,5 Hideo Saji,5 Toshihiko Aso,1 Toshiya Murai,1 Keita Ueda1 1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Medical Innovation Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 3Shiga Medical Center Research Institute, Moriyama, Japan; 4Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan; 5Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, JapanCorrespondence: Shiho UbukataDepartment of Psychiatry, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo, Kyoto 606-8507, JapanTel +81-75-751-4947Email ubukata@kuhp.kyoto-u.ac.jpAim: Amyloid-β (Aβ) accumulation, accelerated by traumatic brain injury (TBI), may play a crucial role in neurodegeneration in chronic-stage TBI. The injury type could influence Aβ dynamics because of TBI’s complex, heterogeneous nature. We, therefore, investigated spatial patterns of amyloid deposition according to injury type after TBI using 5-(5-(2-(2-(2-[F]-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) positron emission tomography (PET).Methods: Altogether, 20 patients with chronic TBI [12 with focal injury, 8 with diffuse axonal injury (DAI)] underwent 18F-FPYBF-2 PET, structural magnetic resonance imaging (MRI), and neuropsychological examination. Additionally, 50 healthy controls underwent either 18F-FPYBF-2 PET (n=30) or structural MRI (n=20).Results: Standardized uptake value ratio (SUVR) on PET images and regional brain volumes were measured in four cortical (frontal, parietal, occipital, temporal) and subcortical (combined caudate, putamen, pallidum, thalamus) regions. Patients with DAI showed significantly increased (compared with controls) SUVR in occipital and temporal cortices and decreased brain volume in occipital cortex (corrected p < 0.05). Although patients with focal injury showed decreased SUVR in all regions except occipital cortex, there were no significant differences (compared with controls) in the SUVR in any regions. There were no significant correlations between increased SUVR and neuropsychological impairments in patients with DAI.Conclusion: Varying spatial patterns of amyloid deposition suggest amyloid pathology diversity depending on the injury type in chronic-TBI patients.Keywords: amyloid deposition, chronic, diffuse axonal injury, focal injury, PET

Michi Ogawa,1 Tasuku Hashimoto,1,2 Mami Tanaka,3 Masumi Tachibana,1 Ryota Seki,1 Aiko Sato,4 Jun Okayama,5 Mamiko Endo,6 Naoki Saito,7 Yasunori Sato,8 Hiroyuki Watanabe,9,10 Michiko Nakazato,1,11 Emi Mori,12 Makio Shozu,13 Masaomi Iyo1 1Department of Psychiatry, Graduate School of Medicine, Chiba University, Chiba, Japan; 2Department of Psychiatry, Satsuki-kai Sodegaura-Satsukidai Hospital, Chiba, Japan; 3Center for Forensic Mental Health, Chiba University, Chiba, Japan; 4Department of Psychiatry, Chiba University Hospital, Chiba, Japan; 5Department of Maternal‐Fetal Medicine, Chiba University Hospital, Chiba, Japan; 6Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan; 7Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan; 8Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan; 9Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan; 10Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan; 11Department of Psychiatry, International University of Health and Welfare Atami Hospital, Atami, Japan; 12Department of Health Promotion Nursing, Graduate School of Nursing, Chiba University, Chiba, Japan; 13Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, JapanCorrespondence: Tasuku HashimotoDepartment of Psychiatry, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, JapanTel +81-43-226-2148Fax +81-43-226-2150Email t-hashimoto@faculty.chiba-u.jpBackground: Pregnant and postpartum women with psychosocial problems are prone to face limited or absent perinatal functional support from biological grandmothers due to familial dysfunction. The study aimed to investigate whether the involvement and presence of biological maternal grandmothers providing practical support for their pre/postnatal daughters (ie, pregnant women) during the perinatal period may influence the number of support services provided by multidisciplinary agencies, including child consultation centers and municipal offices.Participants and methods: This is a retrospective cohort study based on the medical records of all pregnant women with psychosocial problems that visited, gave birth, and received intervention from the hospital-based child protection unit at the Chiba University Hospital between February 2018 to March 2019. The primary outcome was to identify whether there was a difference in the number of multidisciplinary agencies providing perinatal support between pregnant women with and without the presence of functional support from biological maternal grandmothers during the perinatal period.Results: We identified 114 pregnant and postpartum women with psychosocial problems. Seventy-six of these participants (66.7%) had functional support from their biological maternal grandmothers during the perinatal period, and 38 participants (33.3%) did not. The number of agencies involved with participants who lacked functional support was significantly higher than participants with functional support (t(55.14) = 2.98, p < 0.01). This finding was consistent among pregnant and postpartum primipara participants (n = 70) (t(68) = 3.87, p < 0.001), but not multipara (n = 44).Conclusion: The findings indicate that the presence and functional support of biological maternal grandmothers influence the support that is needed from multidisciplinary perinatal support systems by pregnant and postpartum women with psychosocial problems. Primipara mothers without support from their own mothers may need greater multidisciplinary support.Keywords: child maltreatment, grandmother, perinatal, postpartum, pregnancy, psychosocial

Masato Karayama,1 Naoki Inui,1,2 Hideki Yasui,1 Masato Kono,1 Hironao Hozumi,1 Yuzo Suzuki,1 Kazuki Furuhashi,1 Dai Hashimoto,1 Noriyuki Enomoto,1 Tomoyuki Fujisawa,1 Yutaro Nakamura,1 Hiroshi Watanabe,2 Takafumi Suda11Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan; 2Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, JapanPurpose: The diagnosis and severity of chronic obstructive pulmonary disease (COPD) are defined by airflow limitation using spirometry. However, COPD has diverse clinical features, and several phenotypes based on non-spirometric data have been investigated. To identify novel phenotypes of COPD using radiologic data obtained by three-dimensional computed tomography (3D-CT).Patients and methods: The inner luminal area and wall thickness of third- to sixth-generation bronchi and the percentage of the low-attenuation area (less than −950 HU) of the lungs were measured using 3D-CT in patients with COPD. Using the radiologic data, hierarchical clustering was performed. Respiratory reactance and resistance were measured to evaluate functional differences among the clusters.Results: Four clusters were identified among 167 patients with COPD: Cluster I, mild emphysema with severe airway changes, severe airflow limitation, and high exacerbation risk; Cluster II, mild emphysema with moderate airway changes, mild airflow limitation, and mild dyspnea; Cluster III, severe emphysema with moderate airway changes, severe airflow limitation, and increased dyspnea; and Cluster IV, moderate emphysema with mild airway changes, mild airflow limitation, low exacerbation risk, and mild dyspnea. Cluster I had the highest respiratory resistance among the four clusters. Clusters I and III had higher respiratory reactance than Clusters II and IV.Conclusions: The 3D-CT-based radiologic phenotypes were associated with the clinical features of COPD. Measurement of respiratory resistance and reactance may help to identify phenotypic differences.Keywords: airway, chronic obstructive pulmonary disease, clustering analysis, emphysema, phenotype, three-dimensional computed tomography

Saori Nagao,1,2 Kazuaki Taguchi,3 Hiromi Sakai,4 Keishi Yamasaki,3,5 Hiroshi Watanabe,1,6 Masaki Otagiri,3,5 Toru Maruyama1,6 1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 2Research Fellow of Japan Society for the Promotion of Science, Tokyo, 3Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, 4Department of Chemistry, Nara Medical University, Kashihara, 5DDS Research Institute, Sojo University, 6Center for Clinical Pharmaceutical Sciences, School of Pharmacy, Kumamoto University, Kumamoto, Japan Abstract: Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O2-bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage. Keywords: acute pancreatitis, carbon monoxide, CDE diet, liposome, oxidative stress, inflammation

OBJECTIVE: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study. SUBJECTS AND METHODS: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food. RESULTS: We found a 0.60 Spearman's correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson's correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values. CONCLUSIONS: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake. [ABSTRACT FROM AUTHOR]

In ungulate assemblages, although interspecific differences in body size and gregariousness are thought to have a direct impact on winning or losing in interference competition, this has not been fully investigated. We observed a total of 64 instances of interspecific contact between larger-gregarious sika deer and smaller-solitary Japanese serows over eight years field observations. Deer-to-serow aggression were never observed. Whereas, serows showed antagonistic behaviour, such as walk push and chasing, to deer, but could rarely displace deer. Serows showed higher alertness to deer than deer did to serows. These results suggest that larger-gregarious ungulates do not necessarily exclude smaller-solitary ones and serows are sensitive to the presence of deer. Differences in aggressiveness and alertness between deer and serows may reflect differences in territoriality: serows may be more sensitive to the invasion of deer into their territory. Serows' sensitivity to deer may have a negative effect on their population. [ABSTRACT FROM AUTHOR]

A kind of silica nanofibers (SNF) mats with superhydrophobicity and superlipophilicity as well as excellent heat resistance, had been prepared by modifying of 1, 1, 1, 3, 3, 3-hexamethyldisilazane on electrospun SNF mats. The effects of heat treatment time on properties of modified SNF mats were investigated by scanning electron microscopy, nitrogen absorption analysis, X-ray photoelectron spectroscopy, and contact angle measurement. With high specific surface area 240.1 m2/g, the optimal modified SNF mat approached water contact angle (WCA) 153.2° and fuel contact angle (FCA) 0°, furthermore, even after annealing by 450°C in air for 1h , WCA remained at 135.5° and FCA kept at 3.8°, which opened a new way to improve heat resistance of fuel-water filter paper.